tretinoin and Obesity

Congenital heart disease (CHD) has many forms and a wide range of causes. Clinically, it is important to understand the causes. This allows estimation of recurrence rate, guides treatment options, and may also be used to formulate public health advice to reduce the population prevalence of CHD. The recent advent of sophisticated genetic and genomic methods has led to the identification of more than 100 genes associated with CHD. However, despite these great strides, to date only one-third of CHD cases have been shown to have a simple genetic cause. This is because CHD can also be caused by oligogenic factors, environmental factors, and/or gene-environment interaction. Although solid evidence for environmental causes of CHD have been available for almost 80 years, it is only very recently that the molecular mechanisms for these risk factors have begun to be investigated. In this review, we describe the most important environmental CHD risk factors, and what is known about how they cause CHD.

Topics: Alcohol Drinking; Animals; Diabetes Mellitus; Environmental Exposure; Gene-Environment Interaction; Genomics; Heart; Heart Defects, Congenital; Humans; Hyperthermia; Hypoxia; Obesity; Phenylketonurias; Prevalence; Risk Factors; Thalidomide; Tretinoin; Vitamin A

Vitamin A is a fat-soluble essential nutrient obtained from plant- and animal-based sources that has roles in growth, vision, and metabolism. Vitamin A circulates mainly as retinol bound to retinol-binding protein 4 (RBP4), and is delivered to tissues and converted to retinoic acid, which is a ligand for several nuclear receptors. In recent years, aspects of vitamin A metabolism have been under scrutiny with regards to the development of metabolic and lifestyle diseases including cardiovascular disease (CVD), type 2 diabetes mellitus (T2DM), and overweight and obesity in humans. Studies have mainly focused on RBP4 in this context, whereas the major circulating form, retinol, and the major bioactive form, retinoic acid, have been overlooked in this regard until recently. As one of the main roles of RBP4 is to deliver retinol to tissues for biological action, the associations of retinol and retinoic acid with these diseases must also be considered. In this review, we summarize and discuss recent and available evidence from human studies with focus on retinol, retinoic acid, and RBP4 and provide an overview of these crucial components of vitamin A metabolism in CVD, T2DM, and obesity. In summary, retinol was found to be both inversely and positively associated with CVD whereas the associations with T2DM and obesity were less clear. Although only a few studies have been published on retinoic acid, it was inversely associated with CVD. In contrast, serum RBP4 was mostly found to be positively associated with CVD, T2DM, and obesity. At present, it is difficult to ascertain why the reported associations differ depending on the compound under study, but there is a clear imbalance in the literature in disfavor of retinol and retinoic acid, which needs to be considered in future human studies.

Topics: Animals; Cardiovascular Diseases; Diabetes Mellitus, Type 2; Humans; Obesity; Retinol-Binding Proteins, Plasma; Tretinoin; Vitamin A

The gut microbiota is a complex ecosystem consisted of trillions of microbes that have co-evolved with their host for hundreds of millions of years. During the last decade, a growing body of knowledge has suggested that there is a compelling set of connections among diet, gut microbiota and human health. Various physiological functions of the host, ranging from metabolic and immune regulation to nerve and endocrine development, are possibly mediated by the structural components of microbial cell or the products of microbial metabolism, which are greatly influenced by dietary macronutrients and micronutrients. Thus, governing the production and activity of these microbial-associated small molecules and metabolites through dietary intervention may provide promising strategies for the improvement of human health and disease. In this review article, we first provide an overview of current findings about the intimate interrelationships between diet and gut microbiota. We also introduce the physiological effects of some microbial-associated small molecules and metabolites on the host as well as the detailed signaling mechanisms.

Topics: Acetates; Animals; Bile Acids and Salts; Diet; Diet, Western; Dietary Carbohydrates; Dietary Fats; Dietary Fiber; Fatty Acids; Fermentation; Gastrointestinal Microbiome; Health Promotion; Humans; Indoles; Lipopolysaccharides; Nutrients; Obesity; Tretinoin

Middle East Respiratory Syndrome (MERS) is a novel respiratory illness firstly reported in Saudi Arabia in 2012. It is caused by a new corona virus, called MERS corona virus (MERS-CoV). Most people who have MERS-CoV infection developed severe acute respiratory illness.. This work is done to determine the clinical characteristics and the outcome of intensive care unit (ICU) admitted patients with confirmed MERS-CoV infection.. This study included 32 laboratory confirmed MERS corona virus infected patients who were admitted into ICU. It included 20 (62.50%) males and 12 (37.50%) females. The mean age was 43.99 ± 13.03 years. Diagnosis was done by real-time reverse transcription polymerase chain reaction (rRT-PCR) test for corona virus on throat swab, sputum, tracheal aspirate, or bronchoalveolar lavage specimens. Clinical characteristics, co-morbidities and outcome were reported for all subjects.. Most MERS corona patients present with fever, cough, dyspnea, sore throat, runny nose and sputum. The presence of abdominal symptoms may indicate bad prognosis. Prolonged duration of symptoms before patients' hospitalization, prolonged duration of mechanical ventilation and hospital stay, bilateral radiological pulmonary infiltrates, and hypoxemic respiratory failure were found to be strong predictors of mortality in such patients. Also, old age, current smoking, smoking severity, presence of associated co-morbidities like obesity, diabetes mellitus, chronic heart diseases, COPD, malignancy, renal failure, renal transplantation and liver cirrhosis are associated with a poor outcome of ICU admitted MERS corona virus infected patients.. Plasma HO-1, ferritin, p21, and NQO1 were all elevated at baseline in CKD participants. Plasma HO-1 and urine NQO1 levels each inversely correlated with eGFR (. SnPP can be safely administered and, after its injection, the resulting changes in plasma HO-1, NQO1, ferritin, and p21 concentrations can provide information as to antioxidant gene responsiveness/reserves in subjects with and without kidney disease.. A Study with RBT-1, in Healthy Volunteers and Subjects with Stage 3-4 Chronic Kidney Disease, NCT0363002 and NCT03893799.. HFNC did not significantly modify work of breathing in healthy subjects. However, a significant reduction in the minute volume was achieved, capillary [Formula: see text] remaining constant, which suggests a reduction in dead-space ventilation with flows > 20 L/min. (ClinicalTrials.gov registration NCT02495675).. 3 组患者手术时间、术中显性失血量及术后 1 周血红蛋白下降量比较差异均无统计学意义（. 对于肥胖和超重的膝关节单间室骨关节炎患者，采用 UKA 术后可获满意短中期疗效，远期疗效尚需进一步随访观察。.. Decreased muscle strength was identified at both time points in patients with hEDS/HSD. The evolution of most muscle strength parameters over time did not significantly differ between groups. Future studies should focus on the effectiveness of different types of muscle training strategies in hEDS/HSD patients.. These findings support previous adverse findings of e-cigarette exposure on neurodevelopment in a mouse model and provide substantial evidence of persistent adverse behavioral and neuroimmunological consequences to adult offspring following maternal e-cigarette exposure during pregnancy. https://doi.org/10.1289/EHP6067.. This RCT directly compares a neoadjuvant chemotherapy regimen with a standard CROSS regimen in terms of overall survival for patients with locally advanced ESCC. The results of this RCT will provide an answer for the controversy regarding the survival benefits between the two treatment strategies.. NCT04138212, date of registration: October 24, 2019.. Results of current investigation indicated that milk type and post fermentation cooling patterns had a pronounced effect on antioxidant characteristics, fatty acid profile, lipid oxidation and textural characteristics of yoghurt. Buffalo milk based yoghurt had more fat, protein, higher antioxidant capacity and vitamin content. Antioxidant and sensory characteristics of T. If milk is exposed to excessive amounts of light, Vitamins B. The two concentration of ZnO nanoparticles in the ambient air produced two different outcomes. The lower concentration resulted in significant increases in Zn content of the liver while the higher concentration significantly increased Zn in the lungs (p < 0.05). Additionally, at the lower concentration, Zn content was found to be lower in brain tissue (p < 0.05). Using TEM/EDX we detected ZnO nanoparticles inside the cells in the lungs, kidney and liver. Inhaling ZnO NP at the higher concentration increased the levels of mRNA of the following genes in the lungs: Mt2 (2.56 fold), Slc30a1 (1.52 fold) and Slc30a5 (2.34 fold). At the lower ZnO nanoparticle concentration, only Slc30a7 mRNA levels in the lungs were up (1.74 fold). Thus the two air concentrations of ZnO nanoparticles produced distinct effects on the expression of the Zn-homeostasis related genes.. Until adverse health effects of ZnO nanoparticles deposited in organs such as lungs are further investigated and/or ruled out, the exposure to ZnO nanoparticles in aerosols should be avoided or minimised.

Topics: A549 Cells; Acetylmuramyl-Alanyl-Isoglutamine; Acinetobacter baumannii; Acute Lung Injury; Adaptor Proteins, Signal Transducing; Adenine; Adenocarcinoma; Adipogenesis; Administration, Cutaneous; Administration, Ophthalmic; Adolescent; Adsorption; Adult; Aeromonas hydrophila; Aerosols; Aged; Aged, 80 and over; Aging; Agriculture; Air Pollutants; Air Pollution; Airway Remodeling; Alanine Transaminase; Albuminuria; Aldehyde Dehydrogenase 1 Family; Algorithms; AlkB Homolog 2, Alpha-Ketoglutarate-Dependent Dioxygenase; Alzheimer Disease; Amino Acid Sequence; Ammonia; Ammonium Compounds; Anaerobiosis; Anesthetics, Dissociative; Anesthetics, Inhalation; Animals; Anti-Bacterial Agents; Anti-HIV Agents; Anti-Infective Agents; Anti-Inflammatory Agents; Antibiotics, Antineoplastic; Antibodies, Antineutrophil Cytoplasmic; Antibodies, Monoclonal, Humanized; Antifungal Agents; Antigens, Bacterial; Antigens, CD; Antigens, Differentiation, Myelomonocytic; Antimetabolites, Antineoplastic; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Antioxidants; Antitubercular Agents; Antiviral Agents; Apolipoproteins E; Apoptosis; Arabidopsis; Arabidopsis Proteins; Arsenic; Arthritis, Rheumatoid; Asthma; Atherosclerosis; ATP-Dependent Proteases; Attitude of Health Personnel; Australia; Austria; Autophagy; Axitinib; Bacteria; Bacterial Outer Membrane Proteins; Bacterial Proteins; Bacterial Toxins; Bacterial Typing Techniques; Bariatric Surgery; Base Composition; Bayes Theorem; Benzoxazoles; Benzylamines; beta Catenin; Betacoronavirus; Betula; Binding Sites; Biological Availability; Biological Oxygen Demand Analysis; Biomarkers; Biomarkers, Tumor; Biopsy; Bioreactors; Biosensing Techniques; Birth Weight; Blindness; Blood Chemical Analysis; Blood Gas Analysis; Blood Glucose; Blood Pressure; Blood Pressure Monitoring, Ambulatory; Blood-Brain Barrier; Blotting, Western; Body Mass Index; Body Weight; Bone and Bones; Bone Density; Bone Resorption; Borates; Brain; Brain Infarction; Brain Injuries, Traumatic; Brain Neoplasms; Breakfast; Breast Milk Expression; Breast Neoplasms; Bronchi; Bronchoalveolar Lavage Fluid; Buffaloes; Cadherins; Calcification, Physiologic; Calcium Compounds; Calcium, Dietary; Cannula; Caprolactam; Carbon; Carbon Dioxide; Carboplatin; Carcinogenesis; Carcinoma, Ductal; Carcinoma, Ehrlich Tumor; Carcinoma, Hepatocellular; Carcinoma, Non-Small-Cell Lung; Carcinoma, Pancreatic Ductal; Carcinoma, Renal Cell; Cardiovascular Diseases; Carps; Carrageenan; Case-Control Studies; Catalysis; Catalytic Domain; Cattle; CD8-Positive T-Lymphocytes; Cell Adhesion; Cell Cycle Proteins; Cell Death; Cell Differentiation; Cell Line; Cell Line, Tumor; Cell Movement; Cell Nucleus; Cell Phone Use; Cell Proliferation; Cell Survival; Cell Transformation, Neoplastic; Cell Transformation, Viral; Cells, Cultured; Cellulose; Chemical Phenomena; Chemoradiotherapy; Child; Child Development; Child, Preschool; China; Chitosan; Chlorocebus aethiops; Cholecalciferol; Chromatography, Liquid; Circadian Clocks; Circadian Rhythm; Circular Dichroism; Cisplatin; Citric Acid; Clinical Competence; Clinical Laboratory Techniques; Clinical Trials, Phase I as Topic; Clinical Trials, Phase II as Topic; Clostridioides difficile; Clostridium Infections; Coculture Techniques; Cohort Studies; Cold Temperature; Colitis; Collagen Type I; Collagen Type I, alpha 1 Chain; Collagen Type XI; Color; Connective Tissue Diseases; Copper; Coronary Angiography; Coronavirus 3C Proteases; Coronavirus Infections; Cost of Illness; Counselors; COVID-19; COVID-19 Testing; Creatine Kinase; Creatinine; Cross-Over Studies; Cross-Sectional Studies; Cryoelectron Microscopy; Cryosurgery; Crystallography, X-Ray; Cues; Cultural Competency; Cultural Diversity; Curriculum; Cyclic AMP Response Element-Binding Protein; Cyclin-Dependent Kinase Inhibitor p21; Cycloparaffins; Cysteine Endopeptidases; Cytokines; Cytoplasm; Cytoprotection; Databases, Factual; Denitrification; Deoxycytidine; Diabetes Complications; Diabetes Mellitus; Diabetes Mellitus, Experimental; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Diagnosis, Differential; Diatoms; Diet; Diet, High-Fat; Dietary Exposure; Diffusion Magnetic Resonance Imaging; Diketopiperazines; Dipeptidyl Peptidase 4; Dipeptidyl-Peptidase IV Inhibitors; Disease Models, Animal; Disease Progression; Disease-Free Survival; DNA; DNA Damage; DNA Glycosylases; DNA Repair; DNA-Binding Proteins; DNA, Bacterial; DNA, Viral; Docetaxel; Dose Fractionation, Radiation; Dose-Response Relationship, Drug; Down-Regulation; Doxorubicin; Drosophila; Drosophila melanogaster; Drug Carriers; Drug Delivery Systems; Drug Liberation; Drug Repositioning; Drug Resistance, Bacterial; Drug Resistance, Multiple, Bacterial; Drug Resistance, Neoplasm; Drug Screening Assays, Antitumor; Drug Synergism; Drug Therapy, Combination; Edema; Edible Grain; Education, Graduate; Education, Medical, Graduate; Education, Pharmacy; Ehlers-Danlos Syndrome; Electron Transport Complex III; Electron Transport Complex IV; Electronic Nicotine Delivery Systems; Emergency Service, Hospital; Empathy; Emulsions; Endothelial Cells; Endurance Training; Energy Intake; Enterovirus A, Human; Environment; Environmental Monitoring; Enzyme Assays; Enzyme Inhibitors; Epithelial Cells; Epithelial-Mesenchymal Transition; Epoxide Hydrolases; Epoxy Compounds; Erythrocyte Count; Erythrocytes; Escherichia coli; Escherichia coli Infections; Escherichia coli Proteins; Esophageal Neoplasms; Esophageal Squamous Cell Carcinoma; Esophagectomy; Estrogens; Etanercept; Ethiopia; Ethnicity; Ethylenes; Exanthema; Exercise; Exercise Test; Exercise Tolerance; Extracellular Matrix; Extracorporeal Membrane Oxygenation; Eye Infections, Fungal; False Negative Reactions; Fatty Acids; Fecal Microbiota Transplantation; Feces; Female; Femur Neck; Fermentation; Ferritins; Fetal Development; Fibroblast Growth Factor-23; Fibroblast Growth Factors; Fibroblasts; Fibroins; Fish Proteins; Flavanones; Flavonoids; Focus Groups; Follow-Up Studies; Food Handling; Food Supply; Food, Formulated; Forced Expiratory Volume; Forests; Fractures, Bone; Fruit and Vegetable Juices; Fusobacteria; G1 Phase Cell Cycle Checkpoints; G2 Phase Cell Cycle Checkpoints; Gamma Rays; Gastrectomy; Gastrointestinal Microbiome; Gastrointestinal Stromal Tumors; Gefitinib; Gels; Gemcitabine; Gene Amplification; Gene Expression; Gene Expression Regulation; Gene Expression Regulation, Bacterial; Gene Expression Regulation, Neoplastic; Gene Expression Regulation, Plant; Gene Knockdown Techniques; Gene-Environment Interaction; Genotype; Germany; Glioma; Glomerular Filtration Rate; Glucagon; Glucocorticoids; Glycemic Control; Glycerol; Glycogen Synthase Kinase 3 beta; Glycolipids; Glycolysis; Goblet Cells; Gram-Negative Bacterial Infections; Granulocyte Colony-Stimulating Factor; Graphite; Greenhouse Effect; Guanidines; Haemophilus influenzae; HCT116 Cells; Health Knowledge, Attitudes, Practice; Health Personnel; Health Services Accessibility; Health Services Needs and Demand; Health Status Disparities; Healthy Volunteers; Heart Failure; Heart Rate; Heart Transplantation; Heart-Assist Devices; HEK293 Cells; Heme; Heme Oxygenase-1; Hemolysis; Hemorrhage; Hepatitis B; Hepatitis B e Antigens; Hepatitis B Surface Antigens; Hepatitis B virus; Hepatitis B, Chronic; Hepatocytes; Hexoses; High-Throughput Nucleotide Sequencing; Hippo Signaling Pathway; Histamine; Histamine Agonists; Histidine; Histone Deacetylase 2; HIV Infections; HIV Reverse Transcriptase; HIV-1; Homebound Persons; Homeodomain Proteins; Homosexuality, Male; Hospice and Palliative Care Nursing; HSP70 Heat-Shock Proteins; Humans; Hyaluronan Receptors; Hydrogen; Hydrogen Peroxide; Hydrogen-Ion Concentration; Hydrolysis; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypoglycemia; Hypoglycemic Agents; Hypoxia; Idiopathic Interstitial Pneumonias; Imaging, Three-Dimensional; Imatinib Mesylate; Immunotherapy; Implementation Science; Incidence; INDEL Mutation; Induced Pluripotent Stem Cells; Industrial Waste; Infant; Infant, Newborn; Inflammation; Inflammation Mediators; Infliximab; Infusions, Intravenous; Inhibitory Concentration 50; Injections; Insecticides; Insulin-Like Growth Factor Binding Protein 5; Insulin-Secreting Cells; Interleukin-1; Interleukin-17; Interleukin-8; Internship and Residency; Intestines; Intracellular Signaling Peptides and Proteins; Ion Transport; Iridaceae; Iridoid Glucosides; Islets of Langerhans Transplantation; Isodon; Isoflurane; Isotopes; Italy; Joint Instability; Ketamine; Kidney; Kidney Failure, Chronic; Kidney Function Tests; Kidney Neoplasms; Kinetics; Klebsiella pneumoniae; Knee Joint; Kruppel-Like Factor 4; Kruppel-Like Transcription Factors; Lactate Dehydrogenase 5; Laparoscopy; Laser Therapy; Lasers, Semiconductor; Lasers, Solid-State; Laurates; Lead; Leukocyte L1 Antigen Complex; Leukocytes, Mononuclear; Light; Lipid Peroxidation; Lipopolysaccharides; Liposomes; Liver; Liver Cirrhosis; Liver Neoplasms; Liver Transplantation; Locomotion; Longitudinal Studies; Lopinavir; Lower Urinary Tract Symptoms; Lubricants; Lung; Lung Diseases, Interstitial; Lung Neoplasms; Lymphocyte Activation; Lymphocytes, Tumor-Infiltrating; Lymphoma, Mantle-Cell; Lysosomes; Macrophages; Male; Manganese Compounds; MAP Kinase Kinase 4; Mass Screening; Maternal Health; Medicine, Chinese Traditional; Melanoma, Experimental; Memantine; Membrane Glycoproteins; Membrane Proteins; Mesenchymal Stem Cell Transplantation; Metal Nanoparticles; Metalloendopeptidases; Metalloporphyrins; Methadone; Methane; Methicillin-Resistant Staphylococcus aureus; Mexico; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Mice, Inbred ICR; Mice, Knockout; Mice, Nude; Mice, SCID; Mice, Transgenic; Microarray Analysis; Microbial Sensitivity Tests; Microbiota; Micronutrients; MicroRNAs; Microscopy, Confocal; Microsomes, Liver; Middle Aged; Milk; Milk, Human; Minority Groups; Mitochondria; Mitochondrial Membranes; Mitochondrial Proteins; Models, Animal; Models, Molecular; Molecular Conformation; Molecular Docking Simulation; Molecular Dynamics Simulation; Molecular Epidemiology; Molecular Structure; Molecular Weight; Multilocus Sequence Typing; Multimodal Imaging; Muscle Strength; Muscle, Skeletal; Muscular Diseases; Mutation; Mycobacterium tuberculosis; Myocardial Stunning; Myristates; NAD(P)H Dehydrogenase (Quinone); Nanocomposites; Nanogels; Nanoparticles; Nanotechnology; Naphthalenes; Nasal Cavity; National Health Programs; Necrosis; Needs Assessment; Neoadjuvant Therapy; Neonicotinoids; Neoplasm Invasiveness; Neoplasm Metastasis; Neoplasm Proteins; Neoplasm Recurrence, Local; Neoplasm Staging; Neoplasm Transplantation; Neoplasms; Neoplastic Stem Cells; Netherlands; Neuroblastoma; Neuroprotective Agents; Neutrophils; NF-kappa B; NFATC Transcription Factors; Nicotiana; Nicotine; Nitrates; Nitrification; Nitrites; Nitro Compounds; Nitrogen; Nitrogen Dioxide; North Carolina; Nuclear Magnetic Resonance, Biomolecular; Nuclear Proteins; Nucleic Acid Hybridization; Nucleosomes; Nutrients; Obesity; Obesity, Morbid; Oceans and Seas; Oncogene Protein v-akt; Oncogenes; Oocytes; Open Reading Frames; Osteoclasts; Osteogenesis; Osteoporosis; Osteoporosis, Postmenopausal; Outpatients; Ovarian Neoplasms; Ovariectomy; Overweight; Oxazines; Oxidants; Oxidation-Reduction; Oxidative Stress; Oxides; Oxidoreductases; Oxygen; Oxygen Inhalation Therapy; Oxygenators, Membrane; Ozone; Paclitaxel; Paenibacillus; Pain Measurement; Palliative Care; Pancreatic Neoplasms; Pandemics; Parasympathetic Nervous System; Particulate Matter; Pasteurization; Patient Preference; Patient Satisfaction; Pediatric Obesity; Permeability; Peroxiredoxins; Peroxynitrous Acid; Pharmaceutical Services; Pharmacists; Pharmacy; Phaseolus; Phenotype; Phoeniceae; Phosphates; Phosphatidylinositol 3-Kinases; Phospholipid Transfer Proteins; Phospholipids; Phosphorus; Phosphorylation; Photoperiod; Photosynthesis; Phylogeny; Physical Endurance; Physicians; Pilot Projects; Piperidines; Pituitary Adenylate Cyclase-Activating Polypeptide; Plant Extracts; Plant Leaves; Plant Proteins; Plant Roots; Plaque, Atherosclerotic; Pneumonia; Pneumonia, Viral; Point-of-Care Testing; Polyethylene Glycols; Polymers; Polysorbates; Pore Forming Cytotoxic Proteins; Positron Emission Tomography Computed Tomography; Positron-Emission Tomography; Postprandial Period; Poverty; Pre-Exposure Prophylaxis; Prediabetic State; Predictive Value of Tests; Pregnancy; Pregnancy Trimester, First; Pregnancy, High-Risk; Prenatal Exposure Delayed Effects; Pressure; Prevalence; Primary Graft Dysfunction; Primary Health Care; Professional Role; Professionalism; Prognosis; Progression-Free Survival; Prolactin; Promoter Regions, Genetic; Proof of Concept Study; Proportional Hazards Models; Propylene Glycol; Prospective Studies; Prostate; Protein Binding; Protein Biosynthesis; Protein Isoforms; Protein Kinase Inhibitors; Protein Phosphatase 2; Protein Processing, Post-Translational; Protein Serine-Threonine Kinases; Protein Structure, Tertiary; Protein Transport; Proteoglycans; Proteome; Proto-Oncogene Proteins c-akt; Proto-Oncogene Proteins c-myc; Proto-Oncogene Proteins c-ret; Proto-Oncogene Proteins p21(ras); Proton Pumps; Protons; Protoporphyrins; Pseudomonas aeruginosa; Pseudomonas fluorescens; Pulmonary Artery; Pulmonary Disease, Chronic Obstructive; Pulmonary Gas Exchange; Pulmonary Veins; Pyrazoles; Pyridines; Pyrimidines; Qualitative Research; Quinoxalines; Rabbits; Random Allocation; Rats; Rats, Sprague-Dawley; Rats, Wistar; Receptors, Histamine H3; Receptors, Immunologic; Receptors, Transferrin; Recombinant Proteins; Recurrence; Reference Values; Referral and Consultation; Regional Blood Flow; Registries; Regulon; Renal Insufficiency, Chronic; Reperfusion Injury; Repressor Proteins; Reproducibility of Results; Republic of Korea; Research Design; Resistance Training; Respiration, Artificial; Respiratory Distress Syndrome; Respiratory Insufficiency; Resuscitation; Retinal Dehydrogenase; Retreatment; Retrospective Studies; Reverse Transcriptase Inhibitors; Rhinitis, Allergic; Ribosomal Proteins; Ribosomes; Risk Assessment; Risk Factors; Ritonavir; Rivers; RNA Interference; RNA-Seq; RNA, Messenger; RNA, Ribosomal, 16S; RNA, Small Interfering; Rosuvastatin Calcium; Rural Population; Saccharomyces cerevisiae; Saccharomyces cerevisiae Proteins; Salivary Ducts; Salivary Gland Neoplasms; San Francisco; SARS-CoV-2; Satiation; Satiety Response; Schools; Schools, Pharmacy; Seasons; Seawater; Selection, Genetic; Sequence Analysis, DNA; Serine-Threonine Kinase 3; Sewage; Sheep; Sheep, Domestic; Shock, Hemorrhagic; Signal Transduction; Silver; Silymarin; Single Photon Emission Computed Tomography Computed Tomography; Sirolimus; Sirtuin 1; Skin; Skin Neoplasms; Skin Physiological Phenomena; Sleep Initiation and Maintenance Disorders; Social Class; Social Participation; Social Support; Soil; Soil Microbiology; Solutions; Somatomedins; Soot; Specimen Handling; Spectrophotometry, Ultraviolet; Spectroscopy, Fourier Transform Infrared; Spectrum Analysis; Spinal Fractures; Spirometry; Staphylococcus aureus; STAT1 Transcription Factor; STAT3 Transcription Factor; Streptomyces coelicolor; Stress, Psychological; Stroke; Stroke Volume; Structure-Activity Relationship; Students, Medical; Students, Pharmacy; Substance Abuse Treatment Centers; Sulfur Dioxide; Surface Properties; Surface-Active Agents; Surveys and Questionnaires; Survival Analysis; Survival Rate; Survivin; Sweden; Swine; Swine, Miniature; Sympathetic Nervous System; T-Lymphocytes, Regulatory; Talaromyces; Tandem Mass Spectrometry; tau Proteins; Telemedicine; Telomerase; Telomere; Telomere Homeostasis; Temperature; Terminally Ill; Th1 Cells; Thiamethoxam; Thiazoles; Thiophenes; Thioredoxin Reductase 1; Thrombosis; Thulium; Thyroid Cancer, Papillary; Thyroid Carcinoma, Anaplastic; Thyroid Neoplasms; Time Factors; Titanium; Tomography, Emission-Computed, Single-Photon; Tomography, X-Ray Computed; TOR Serine-Threonine Kinases; Transcription Factor AP-1; Transcription Factors; Transcription, Genetic; Transcriptional Activation; Transcriptome; Transforming Growth Factor beta1; Transistors, Electronic; Translational Research, Biomedical; Transplantation Tolerance; Transplantation, Homologous; Transportation; Treatment Outcome; Tretinoin; Tuberculosis, Multidrug-Resistant; Tuberculosis, Pulmonary; Tubulin Modulators; Tumor Microenvironment; Tumor Necrosis Factor Inhibitors; Tumor Necrosis Factor-alpha; Twins; Ultrasonic Therapy; Ultrasonography; Ultraviolet Rays; United States; Up-Regulation; Uranium; Urethra; Urinary Bladder; Urodynamics; Uromodulin; Uveitis; Vasoconstrictor Agents; Ventricular Function, Left; Vero Cells; Vesicular Transport Proteins; Viral Nonstructural Proteins; Visual Acuity; Vital Capacity; Vitamin D; Vitamin D Deficiency; Vitamin K 2; Vitamins; Volatilization; Voriconazole; Waiting Lists; Waste Disposal, Fluid; Wastewater; Water Pollutants, Chemical; Whole Genome Sequencing; Wine; Wnt Signaling Pathway; Wound Healing; Wounds and Injuries; WW Domains; X-linked Nuclear Protein; X-Ray Diffraction; Xanthines; Xenograft Model Antitumor Assays; YAP-Signaling Proteins; Yogurt; Young Adult; Zebrafish; Zebrafish Proteins; Ziziphus

Obesity and its related metabolic disorders are serious health problems worldwide, and lead to various health-related complications, including cancer. Among human cancers, hepatocellular carcinoma (HCC) is one of the most common malignancies affected by obesity. Therefore, obesity and its related disorders might be a key target for the prevention of HCC. Recently, new research indicates that the molecular abnormalities associated with obesity, including insulin resistance/hyperinsulinemia, chronic inflammation, adipokine imbalance, and oxidative stress, are possible molecular mechanisms underlying the pathogenesis of obesity-related hepatocarcinogenesis. Green tea catechins and branched-chain amino acids, both of which are classified as nutraceutical agents, have been reported to prevent obesity-related HCC development by improving metabolic abnormalities. The administration of acyclic retinoid, a pharmaceutical agent, reduced the incidence of HCC in obese and diabetic mice, and was also associated with improvements in insulin resistance and chronic inflammation. In this article, we review the detailed molecular mechanisms that link obesity to the development of HCC in obese individuals. We also summarize recent evidence from experimental and clinical studies using either nutraceutical or pharmaceutical agents, and suggest that nutraceutical and pharmaceutical approaches targeting metabolic abnormalities might be a promising strategy to prevent the development of obesity-related HCC.

Topics: Amino Acids, Branched-Chain; Animals; Carcinoma, Hepatocellular; Catechin; Chemoprevention; Diabetes Mellitus, Experimental; Dietary Supplements; Humans; Liver Neoplasms; Mice; Non-alcoholic Fatty Liver Disease; Obesity; Tea; Tretinoin

It has long been established that the transcriptional activity of retinoic acid (RA) is mediated by members of the nuclear receptor family of ligand-activated transcription factors termed RA receptors (RARs). More recent observations have established that RA also activates an additional nuclear receptor, PPARβ/δ. Partitioning RA between RARs and PPARβ/δ is governed by different intracellular lipid-binding proteins: cellular RA binding protein 2 (CRABP2) delivers RA to nuclear RARs and a fatty acid binding protein (FABP5) delivers the hormone from the cytosol to nuclear PPARβ/δ. Consequently, RA signals through RARs in CRABP2-expressing cells, but activates PPARβ/δ in cells that express a high level of FABP5. RA elicits different and sometimes opposing responses in cells that express different FABP5/CRABP2 ratios because PPARβ/δ and RARs regulate the expression of distinct sets of genes. An overview of the observations that led to the discovery of this non-classical activity of RA are presented here, along with a discussion of evidence demonstrating the involvement of the dual transcriptional activities of RA in regulating energy homeostasis, insulin responses, and adipocyte and neuron differentiation.

Topics: Adipogenesis; Adipose Tissue; Animals; Biological Transport; Fatty Acid-Binding Proteins; Forecasting; Gene Expression Regulation; Gene Expression Regulation, Neoplastic; Humans; Models, Molecular; Neoplasm Proteins; Neurogenesis; Obesity; PPAR delta; PPAR-beta; Protein Conformation; Receptors, Retinoic Acid; Transcription, Genetic; Tretinoin

In this review, we summarize recent advances in understanding vitamin A-dependent regulation of sex-specific differences in metabolic diseases, inflammation, and certain cancers. We focus on the characterization of the aldehyde dehydrogenase-1 family of enzymes (ALDH1A1, ALDH1A2, ALDH1A3) that catalyze conversion of retinaldehyde to retinoic acid. Additionally, we propose a "horizontal transfer of signaling" from estrogen to retinoids through the action of ALDH1A1. Although estrogen does not directly influence expression of Aldh1a1, it has the ability to suppress Aldh1a2 and Aldh1a3, thereby establishing a female-specific mechanism for retinoic acid generation in target tissues. ALDH1A1 regulates adipogenesis, abdominal fat formation, glucose tolerance, and suppression of thermogenesis in adipocytes; in B cells, ALDH1A1 plays a protective role by inducing oncogene suppressors Rara and Pparg. Considering the conflicting responses of Aldh1a1 in a multitude of physiological processes, only tissue-specific regulation of Aldh1a1 can result in therapeutic effects. We have shown through successful implantation of tissue-specific Aldh1a1-/- preadipocytes that thermogenesis can be induced in wild-type adipose tissues to resolve diet-induced visceral obesity in females. We will briefly discuss the emerging role of ALDH1A1 in multiple myeloma, the regulation of reproduction, and immune responses, and conclude by discussing the role of ALDH1A1 in future therapeutic applications.

Topics: Adipocytes; Adipogenesis; Adipose Tissue, White; Aldehyde Dehydrogenase; Aldehyde Dehydrogenase 1 Family; Animals; Body Fat Distribution; Chronic Disease; Cytokines; Diet; Disease Models, Animal; Estradiol; Female; Humans; Obesity; Polycystic Ovary Syndrome; Retinal Dehydrogenase; Retinaldehyde; Risk Factors; Sex Factors; Thermogenesis; Tretinoin

Abdominal fat formation has become a permanent risk factor for metabolic syndrome and various cancers in one-third of the world's population of obese and even lean patients. Formation of abdominal fat involves additional mechanisms beyond an imbalance in energy intake and expenditure, which explains systemic obesity. In this review, we briefly summarized autonomous regulatory circuits that locally produce hormones from inactive precursors or nutrients for intra-/auto-/paracrine signaling in white adipose depots. Enzymatic pathways activating steroid and thyroid hormones in adipose depots were compared with enzymatic production of retinoic acid from vitamin A. We discussed the role of intracrine circuits in fat-depot functions and strategies to reduce abdominal adiposity through thermogenic adipocytes with interrupted generation of retinoic acid.

Topics: Abdominal Fat; Adipocytes; Adipose Tissue, White; Aromatase; Humans; Hydrocortisone; Iodide Peroxidase; Obesity; Paracrine Communication; Signal Transduction; Tretinoin; Vitamin A

Morbidity and mortality associated with increased white fat accumulation in visceral fat depots have focused attention on the pathways regulating the development of this tissue during embryogenesis, in adulthood, and while under the influence of obesogenic diets. Adipocytes undergo clonal expansion, differentiation (adipogenesis) and maturation through a complex network of transcriptional factors, most of which are expressed at similar levels in visceral and subcutaneous fat. Rigorous research attempts to unfold the pathways regulating expression and activity of adipogenic transcription factors that act in a fat-depot-specific manner. Peroxisome proliferator-activated receptor-γ (PPARγ) is the master regulator of adipogenesis, and is expressed at higher levels in subcutaneous than in visceral depots. PPARγ expression in adipogenesis is mediated by CCAAT/enhancer binding proteins (C/EBPs) and several transcription factors acting in conjunction with C/EBPs, although alternative pathways through zinc-finger protein-423 (ZFP423) transcription factor are sufficient to induce PPARγ expression and adipogenesis. Vitamin A and its metabolites, retinaldehyde and retinoic acid, are transcriptionally-active molecules. Retinoic acid is generated from retinaldehyde in adipose tissue by the aldehyde dehydrogenase-1 family of enzymes (Aldh1). In this review, we discuss the role of Aldh1 enzymes in the generation of retinoic acid during adipogenesis, in the regulation of the transcriptional network of PPARγ in a fat-depot-specific manner, and the important contribution of this autocrine pathway in the development of visceral obesity. This article is part of a Special Issue entitled Retinoid and Lipid Metabolism.

Topics: Adipogenesis; Adipose Tissue, White; Aldehyde Dehydrogenase 1 Family; Animals; CCAAT-Enhancer-Binding Proteins; DNA-Binding Proteins; Humans; Isoenzymes; Mice; Mice, Knockout; Obesity; PPAR gamma; Rats; Retinal Dehydrogenase; Transcription Factors; Tretinoin

Retinoic acid (RA) was found to be a ligand for peroxisome proliferation-activated receptor delta (PPARdelta) as well as the classical RA receptor (RAR). Carrier proteins that move the RA from the cytosol into the nucleus are the fatty acid-binding protein 5 (FABP5), activating PPARdelta, and the cellular retinoic acid-binding protein II (CRABPII), activating RAR. The ratio of FABP5/CRABPII concentrations determines which receptor is activated. By activating PPARdelta, RA was found to induce expression of genes affecting lipid and glucose homeostasis, in particular, leading to expression of the insulin-signaling gene PDK1 and improvement of insulin action. Hence, RA stimulates lipolysis and reduces triglyceride content. In vivo, obesity has led to downregulation of adipose PPARdelta expression. RA implantation into obese mice has caused upregulation of levels of PPARdelta and consequent weight loss as well as increased expression of PPARdelta target genes, including the insulin-signaling gene PDK1.

Topics: Animals; Enzyme Activation; Fatty Acid-Binding Proteins; Humans; Insulin Resistance; Ligands; Lipid Metabolism; Obesity; PPAR delta; Receptors, Retinoic Acid; Tretinoin

Topics: Amino Acids, Branched-Chain; Angiotensin-Converting Enzyme Inhibitors; Antineoplastic Agents; Carcinoma, Hepatocellular; Diabetes Mellitus; Humans; Immunotherapy, Adoptive; Interferons; Lamivudine; Liver Neoplasms; Neoadjuvant Therapy; Neoplasm Recurrence, Local; Obesity; Randomized Controlled Trials as Topic; Risk Factors; Tretinoin; Vitamin K

Significant advances have been made recently toward understanding the molecular events that regulate adipocyte differentiation. In vitro models of adipogenesis, such as the 3T3-L1 and F-442A preadipocyte cell lines have proven to be an invaluable resource in elucidating mechanisms of adipocyte differentiation. Subject to modulation by hormonal, dietary, and genetic influences, the differentiation program now appears to be distinctly controlled through the coordinate regulation of transcription factors that predominantly include members of the C/EBP and PPAR families. Increased understanding of these critical factors and how they are regulated will provide insights into adipose tissue development as well as treatment of obesity.

Topics: 3T3 Cells; Adipocytes; Animals; Calcium-Binding Proteins; CCAAT-Enhancer-Binding Proteins; Cell Differentiation; DNA-Binding Proteins; Gene Expression Regulation, Developmental; Growth Inhibitors; Humans; Intercellular Signaling Peptides and Proteins; Membrane Proteins; Mice; Nuclear Proteins; Obesity; Receptors, Cytoplasmic and Nuclear; Repressor Proteins; Retinoblastoma Protein; Sterol Regulatory Element Binding Protein 1; Transcription Factor AP-2; Transcription Factors; Tretinoin; Tumor Necrosis Factor-alpha

Vitamin A and its metabolites (called retinoids) have been thought to play a role in the development of idiopathic intracranial hypertension (IIH). The IIH Treatment Trial (IIHTT) showed the efficacy of acetazolamide (ACZ) in improving visual field function, papilledema grade, quality of life and cerebrospinal fluid (CSF) pressure. We postulated that IIH patients would demonstrate elevated measures of vitamin A metabolites in the serum and CSF.. Comprehensive measures of serum vitamin A and its metabolites were obtained from 96 IIHTT subjects, randomly assigned to treatment with ACZ or placebo, and 25 controls with similar gender, age and body mass index (BMI). These included retinol, retinol binding protein, all-trans retinoic acid (ATRA), alpha- and beta-carotenes, and beta-cryptoxanthin. The IIHTT subjects also had CSF and serum vitamin A and metabolite measurements obtained at study entry and at six months.. At study entry, of the vitamin A metabolites only serum ATRA was significantly different in IIHTT subjects (median 4.33nM) and controls (median 5.04nM, p=0.02). The BMI of IIHTT subjects showed mild significant negative correlations with serum ATRA, alpha- and beta-carotene, and beta-cryptoxanthin. In contrast, the control subject BMI correlated only with serum ATRA. At six months, the serum retinol, alpha-carotene, beta-carotene, and CSF retinol were increased from baseline in the ACZ treated group, but only increases in alpha-carotene (p=0.02) and CSF ATRA (p=0.04) were significantly greater in the ACZ group compared with the placebo group. No other vitamin A measures were significantly altered over the six months in either treatment group. Weight loss correlated with only with the change in serum beta-carotene (r=-0.44, p=0.006) and the change in CSF retinol (r=-0.61, p=0.02).. Vitamin A toxicity is unlikely a contributory factor in the causation of IIH. Our findings differ from those of prior reports in part because of our use of more accurate quantitative methods and measuring vitamin A metabolites in both serum and CSF. ACZ may alter retinoid metabolism in IIH patients.

Topics: Acetazolamide; Adult; Anticonvulsants; Carotenoids; Chromatography, High Pressure Liquid; Chromatography, Liquid; Female; Follow-Up Studies; Humans; Male; Mass Spectrometry; Obesity; Pseudotumor Cerebri; Retinol-Binding Proteins; Tretinoin; Visual Fields; Vitamin A; Young Adult

Middle East Respiratory Syndrome (MERS) is a novel respiratory illness firstly reported in Saudi Arabia in 2012. It is caused by a new corona virus, called MERS corona virus (MERS-CoV). Most people who have MERS-CoV infection developed severe acute respiratory illness.. This work is done to determine the clinical characteristics and the outcome of intensive care unit (ICU) admitted patients with confirmed MERS-CoV infection.. This study included 32 laboratory confirmed MERS corona virus infected patients who were admitted into ICU. It included 20 (62.50%) males and 12 (37.50%) females. The mean age was 43.99 ± 13.03 years. Diagnosis was done by real-time reverse transcription polymerase chain reaction (rRT-PCR) test for corona virus on throat swab, sputum, tracheal aspirate, or bronchoalveolar lavage specimens. Clinical characteristics, co-morbidities and outcome were reported for all subjects.. Most MERS corona patients present with fever, cough, dyspnea, sore throat, runny nose and sputum. The presence of abdominal symptoms may indicate bad prognosis. Prolonged duration of symptoms before patients' hospitalization, prolonged duration of mechanical ventilation and hospital stay, bilateral radiological pulmonary infiltrates, and hypoxemic respiratory failure were found to be strong predictors of mortality in such patients. Also, old age, current smoking, smoking severity, presence of associated co-morbidities like obesity, diabetes mellitus, chronic heart diseases, COPD, malignancy, renal failure, renal transplantation and liver cirrhosis are associated with a poor outcome of ICU admitted MERS corona virus infected patients.. Plasma HO-1, ferritin, p21, and NQO1 were all elevated at baseline in CKD participants. Plasma HO-1 and urine NQO1 levels each inversely correlated with eGFR (. SnPP can be safely administered and, after its injection, the resulting changes in plasma HO-1, NQO1, ferritin, and p21 concentrations can provide information as to antioxidant gene responsiveness/reserves in subjects with and without kidney disease.. A Study with RBT-1, in Healthy Volunteers and Subjects with Stage 3-4 Chronic Kidney Disease, NCT0363002 and NCT03893799.. HFNC did not significantly modify work of breathing in healthy subjects. However, a significant reduction in the minute volume was achieved, capillary [Formula: see text] remaining constant, which suggests a reduction in dead-space ventilation with flows > 20 L/min. (ClinicalTrials.gov registration NCT02495675).. 3 组患者手术时间、术中显性失血量及术后 1 周血红蛋白下降量比较差异均无统计学意义（. 对于肥胖和超重的膝关节单间室骨关节炎患者，采用 UKA 术后可获满意短中期疗效，远期疗效尚需进一步随访观察。.. Decreased muscle strength was identified at both time points in patients with hEDS/HSD. The evolution of most muscle strength parameters over time did not significantly differ between groups. Future studies should focus on the effectiveness of different types of muscle training strategies in hEDS/HSD patients.. These findings support previous adverse findings of e-cigarette exposure on neurodevelopment in a mouse model and provide substantial evidence of persistent adverse behavioral and neuroimmunological consequences to adult offspring following maternal e-cigarette exposure during pregnancy. https://doi.org/10.1289/EHP6067.. This RCT directly compares a neoadjuvant chemotherapy regimen with a standard CROSS regimen in terms of overall survival for patients with locally advanced ESCC. The results of this RCT will provide an answer for the controversy regarding the survival benefits between the two treatment strategies.. NCT04138212, date of registration: October 24, 2019.. Results of current investigation indicated that milk type and post fermentation cooling patterns had a pronounced effect on antioxidant characteristics, fatty acid profile, lipid oxidation and textural characteristics of yoghurt. Buffalo milk based yoghurt had more fat, protein, higher antioxidant capacity and vitamin content. Antioxidant and sensory characteristics of T. If milk is exposed to excessive amounts of light, Vitamins B. The two concentration of ZnO nanoparticles in the ambient air produced two different outcomes. The lower concentration resulted in significant increases in Zn content of the liver while the higher concentration significantly increased Zn in the lungs (p < 0.05). Additionally, at the lower concentration, Zn content was found to be lower in brain tissue (p < 0.05). Using TEM/EDX we detected ZnO nanoparticles inside the cells in the lungs, kidney and liver. Inhaling ZnO NP at the higher concentration increased the levels of mRNA of the following genes in the lungs: Mt2 (2.56 fold), Slc30a1 (1.52 fold) and Slc30a5 (2.34 fold). At the lower ZnO nanoparticle concentration, only Slc30a7 mRNA levels in the lungs were up (1.74 fold). Thus the two air concentrations of ZnO nanoparticles produced distinct effects on the expression of the Zn-homeostasis related genes.. Until adverse health effects of ZnO nanoparticles deposited in organs such as lungs are further investigated and/or ruled out, the exposure to ZnO nanoparticles in aerosols should be avoided or minimised.

Topics: A549 Cells; Acetylmuramyl-Alanyl-Isoglutamine; Acinetobacter baumannii; Acute Lung Injury; Adaptor Proteins, Signal Transducing; Adenine; Adenocarcinoma; Adipogenesis; Administration, Cutaneous; Administration, Ophthalmic; Adolescent; Adsorption; Adult; Aeromonas hydrophila; Aerosols; Aged; Aged, 80 and over; Aging; Agriculture; Air Pollutants; Air Pollution; Airway Remodeling; Alanine Transaminase; Albuminuria; Aldehyde Dehydrogenase 1 Family; Algorithms; AlkB Homolog 2, Alpha-Ketoglutarate-Dependent Dioxygenase; Alzheimer Disease; Amino Acid Sequence; Ammonia; Ammonium Compounds; Anaerobiosis; Anesthetics, Dissociative; Anesthetics, Inhalation; Animals; Anti-Bacterial Agents; Anti-HIV Agents; Anti-Infective Agents; Anti-Inflammatory Agents; Antibiotics, Antineoplastic; Antibodies, Antineutrophil Cytoplasmic; Antibodies, Monoclonal, Humanized; Antifungal Agents; Antigens, Bacterial; Antigens, CD; Antigens, Differentiation, Myelomonocytic; Antimetabolites, Antineoplastic; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Antioxidants; Antitubercular Agents; Antiviral Agents; Apolipoproteins E; Apoptosis; Arabidopsis; Arabidopsis Proteins; Arsenic; Arthritis, Rheumatoid; Asthma; Atherosclerosis; ATP-Dependent Proteases; Attitude of Health Personnel; Australia; Austria; Autophagy; Axitinib; Bacteria; Bacterial Outer Membrane Proteins; Bacterial Proteins; Bacterial Toxins; Bacterial Typing Techniques; Bariatric Surgery; Base Composition; Bayes Theorem; Benzoxazoles; Benzylamines; beta Catenin; Betacoronavirus; Betula; Binding Sites; Biological Availability; Biological Oxygen Demand Analysis; Biomarkers; Biomarkers, Tumor; Biopsy; Bioreactors; Biosensing Techniques; Birth Weight; Blindness; Blood Chemical Analysis; Blood Gas Analysis; Blood Glucose; Blood Pressure; Blood Pressure Monitoring, Ambulatory; Blood-Brain Barrier; Blotting, Western; Body Mass Index; Body Weight; Bone and Bones; Bone Density; Bone Resorption; Borates; Brain; Brain Infarction; Brain Injuries, Traumatic; Brain Neoplasms; Breakfast; Breast Milk Expression; Breast Neoplasms; Bronchi; Bronchoalveolar Lavage Fluid; Buffaloes; Cadherins; Calcification, Physiologic; Calcium Compounds; Calcium, Dietary; Cannula; Caprolactam; Carbon; Carbon Dioxide; Carboplatin; Carcinogenesis; Carcinoma, Ductal; Carcinoma, Ehrlich Tumor; Carcinoma, Hepatocellular; Carcinoma, Non-Small-Cell Lung; Carcinoma, Pancreatic Ductal; Carcinoma, Renal Cell; Cardiovascular Diseases; Carps; Carrageenan; Case-Control Studies; Catalysis; Catalytic Domain; Cattle; CD8-Positive T-Lymphocytes; Cell Adhesion; Cell Cycle Proteins; Cell Death; Cell Differentiation; Cell Line; Cell Line, Tumor; Cell Movement; Cell Nucleus; Cell Phone Use; Cell Proliferation; Cell Survival; Cell Transformation, Neoplastic; Cell Transformation, Viral; Cells, Cultured; Cellulose; Chemical Phenomena; Chemoradiotherapy; Child; Child Development; Child, Preschool; China; Chitosan; Chlorocebus aethiops; Cholecalciferol; Chromatography, Liquid; Circadian Clocks; Circadian Rhythm; Circular Dichroism; Cisplatin; Citric Acid; Clinical Competence; Clinical Laboratory Techniques; Clinical Trials, Phase I as Topic; Clinical Trials, Phase II as Topic; Clostridioides difficile; Clostridium Infections; Coculture Techniques; Cohort Studies; Cold Temperature; Colitis; Collagen Type I; Collagen Type I, alpha 1 Chain; Collagen Type XI; Color; Connective Tissue Diseases; Copper; Coronary Angiography; Coronavirus 3C Proteases; Coronavirus Infections; Cost of Illness; Counselors; COVID-19; COVID-19 Testing; Creatine Kinase; Creatinine; Cross-Over Studies; Cross-Sectional Studies; Cryoelectron Microscopy; Cryosurgery; Crystallography, X-Ray; Cues; Cultural Competency; Cultural Diversity; Curriculum; Cyclic AMP Response Element-Binding Protein; Cyclin-Dependent Kinase Inhibitor p21; Cycloparaffins; Cysteine Endopeptidases; Cytokines; Cytoplasm; Cytoprotection; Databases, Factual; Denitrification; Deoxycytidine; Diabetes Complications; Diabetes Mellitus; Diabetes Mellitus, Experimental; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Diagnosis, Differential; Diatoms; Diet; Diet, High-Fat; Dietary Exposure; Diffusion Magnetic Resonance Imaging; Diketopiperazines; Dipeptidyl Peptidase 4; Dipeptidyl-Peptidase IV Inhibitors; Disease Models, Animal; Disease Progression; Disease-Free Survival; DNA; DNA Damage; DNA Glycosylases; DNA Repair; DNA-Binding Proteins; DNA, Bacterial; DNA, Viral; Docetaxel; Dose Fractionation, Radiation; Dose-Response Relationship, Drug; Down-Regulation; Doxorubicin; Drosophila; Drosophila melanogaster; Drug Carriers; Drug Delivery Systems; Drug Liberation; Drug Repositioning; Drug Resistance, Bacterial; Drug Resistance, Multiple, Bacterial; Drug Resistance, Neoplasm; Drug Screening Assays, Antitumor; Drug Synergism; Drug Therapy, Combination; Edema; Edible Grain; Education, Graduate; Education, Medical, Graduate; Education, Pharmacy; Ehlers-Danlos Syndrome; Electron Transport Complex III; Electron Transport Complex IV; Electronic Nicotine Delivery Systems; Emergency Service, Hospital; Empathy; Emulsions; Endothelial Cells; Endurance Training; Energy Intake; Enterovirus A, Human; Environment; Environmental Monitoring; Enzyme Assays; Enzyme Inhibitors; Epithelial Cells; Epithelial-Mesenchymal Transition; Epoxide Hydrolases; Epoxy Compounds; Erythrocyte Count; Erythrocytes; Escherichia coli; Escherichia coli Infections; Escherichia coli Proteins; Esophageal Neoplasms; Esophageal Squamous Cell Carcinoma; Esophagectomy; Estrogens; Etanercept; Ethiopia; Ethnicity; Ethylenes; Exanthema; Exercise; Exercise Test; Exercise Tolerance; Extracellular Matrix; Extracorporeal Membrane Oxygenation; Eye Infections, Fungal; False Negative Reactions; Fatty Acids; Fecal Microbiota Transplantation; Feces; Female; Femur Neck; Fermentation; Ferritins; Fetal Development; Fibroblast Growth Factor-23; Fibroblast Growth Factors; Fibroblasts; Fibroins; Fish Proteins; Flavanones; Flavonoids; Focus Groups; Follow-Up Studies; Food Handling; Food Supply; Food, Formulated; Forced Expiratory Volume; Forests; Fractures, Bone; Fruit and Vegetable Juices; Fusobacteria; G1 Phase Cell Cycle Checkpoints; G2 Phase Cell Cycle Checkpoints; Gamma Rays; Gastrectomy; Gastrointestinal Microbiome; Gastrointestinal Stromal Tumors; Gefitinib; Gels; Gemcitabine; Gene Amplification; Gene Expression; Gene Expression Regulation; Gene Expression Regulation, Bacterial; Gene Expression Regulation, Neoplastic; Gene Expression Regulation, Plant; Gene Knockdown Techniques; Gene-Environment Interaction; Genotype; Germany; Glioma; Glomerular Filtration Rate; Glucagon; Glucocorticoids; Glycemic Control; Glycerol; Glycogen Synthase Kinase 3 beta; Glycolipids; Glycolysis; Goblet Cells; Gram-Negative Bacterial Infections; Granulocyte Colony-Stimulating Factor; Graphite; Greenhouse Effect; Guanidines; Haemophilus influenzae; HCT116 Cells; Health Knowledge, Attitudes, Practice; Health Personnel; Health Services Accessibility; Health Services Needs and Demand; Health Status Disparities; Healthy Volunteers; Heart Failure; Heart Rate; Heart Transplantation; Heart-Assist Devices; HEK293 Cells; Heme; Heme Oxygenase-1; Hemolysis; Hemorrhage; Hepatitis B; Hepatitis B e Antigens; Hepatitis B Surface Antigens; Hepatitis B virus; Hepatitis B, Chronic; Hepatocytes; Hexoses; High-Throughput Nucleotide Sequencing; Hippo Signaling Pathway; Histamine; Histamine Agonists; Histidine; Histone Deacetylase 2; HIV Infections; HIV Reverse Transcriptase; HIV-1; Homebound Persons; Homeodomain Proteins; Homosexuality, Male; Hospice and Palliative Care Nursing; HSP70 Heat-Shock Proteins; Humans; Hyaluronan Receptors; Hydrogen; Hydrogen Peroxide; Hydrogen-Ion Concentration; Hydrolysis; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypoglycemia; Hypoglycemic Agents; Hypoxia; Idiopathic Interstitial Pneumonias; Imaging, Three-Dimensional; Imatinib Mesylate; Immunotherapy; Implementation Science; Incidence; INDEL Mutation; Induced Pluripotent Stem Cells; Industrial Waste; Infant; Infant, Newborn; Inflammation; Inflammation Mediators; Infliximab; Infusions, Intravenous; Inhibitory Concentration 50; Injections; Insecticides; Insulin-Like Growth Factor Binding Protein 5; Insulin-Secreting Cells; Interleukin-1; Interleukin-17; Interleukin-8; Internship and Residency; Intestines; Intracellular Signaling Peptides and Proteins; Ion Transport; Iridaceae; Iridoid Glucosides; Islets of Langerhans Transplantation; Isodon; Isoflurane; Isotopes; Italy; Joint Instability; Ketamine; Kidney; Kidney Failure, Chronic; Kidney Function Tests; Kidney Neoplasms; Kinetics; Klebsiella pneumoniae; Knee Joint; Kruppel-Like Factor 4; Kruppel-Like Transcription Factors; Lactate Dehydrogenase 5; Laparoscopy; Laser Therapy; Lasers, Semiconductor; Lasers, Solid-State; Laurates; Lead; Leukocyte L1 Antigen Complex; Leukocytes, Mononuclear; Light; Lipid Peroxidation; Lipopolysaccharides; Liposomes; Liver; Liver Cirrhosis; Liver Neoplasms; Liver Transplantation; Locomotion; Longitudinal Studies; Lopinavir; Lower Urinary Tract Symptoms; Lubricants; Lung; Lung Diseases, Interstitial; Lung Neoplasms; Lymphocyte Activation; Lymphocytes, Tumor-Infiltrating; Lymphoma, Mantle-Cell; Lysosomes; Macrophages; Male; Manganese Compounds; MAP Kinase Kinase 4; Mass Screening; Maternal Health; Medicine, Chinese Traditional; Melanoma, Experimental; Memantine; Membrane Glycoproteins; Membrane Proteins; Mesenchymal Stem Cell Transplantation; Metal Nanoparticles; Metalloendopeptidases; Metalloporphyrins; Methadone; Methane; Methicillin-Resistant Staphylococcus aureus; Mexico; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Mice, Inbred ICR; Mice, Knockout; Mice, Nude; Mice, SCID; Mice, Transgenic; Microarray Analysis; Microbial Sensitivity Tests; Microbiota; Micronutrients; MicroRNAs; Microscopy, Confocal; Microsomes, Liver; Middle Aged; Milk; Milk, Human; Minority Groups; Mitochondria; Mitochondrial Membranes; Mitochondrial Proteins; Models, Animal; Models, Molecular; Molecular Conformation; Molecular Docking Simulation; Molecular Dynamics Simulation; Molecular Epidemiology; Molecular Structure; Molecular Weight; Multilocus Sequence Typing; Multimodal Imaging; Muscle Strength; Muscle, Skeletal; Muscular Diseases; Mutation; Mycobacterium tuberculosis; Myocardial Stunning; Myristates; NAD(P)H Dehydrogenase (Quinone); Nanocomposites; Nanogels; Nanoparticles; Nanotechnology; Naphthalenes; Nasal Cavity; National Health Programs; Necrosis; Needs Assessment; Neoadjuvant Therapy; Neonicotinoids; Neoplasm Invasiveness; Neoplasm Metastasis; Neoplasm Proteins; Neoplasm Recurrence, Local; Neoplasm Staging; Neoplasm Transplantation; Neoplasms; Neoplastic Stem Cells; Netherlands; Neuroblastoma; Neuroprotective Agents; Neutrophils; NF-kappa B; NFATC Transcription Factors; Nicotiana; Nicotine; Nitrates; Nitrification; Nitrites; Nitro Compounds; Nitrogen; Nitrogen Dioxide; North Carolina; Nuclear Magnetic Resonance, Biomolecular; Nuclear Proteins; Nucleic Acid Hybridization; Nucleosomes; Nutrients; Obesity; Obesity, Morbid; Oceans and Seas; Oncogene Protein v-akt; Oncogenes; Oocytes; Open Reading Frames; Osteoclasts; Osteogenesis; Osteoporosis; Osteoporosis, Postmenopausal; Outpatients; Ovarian Neoplasms; Ovariectomy; Overweight; Oxazines; Oxidants; Oxidation-Reduction; Oxidative Stress; Oxides; Oxidoreductases; Oxygen; Oxygen Inhalation Therapy; Oxygenators, Membrane; Ozone; Paclitaxel; Paenibacillus; Pain Measurement; Palliative Care; Pancreatic Neoplasms; Pandemics; Parasympathetic Nervous System; Particulate Matter; Pasteurization; Patient Preference; Patient Satisfaction; Pediatric Obesity; Permeability; Peroxiredoxins; Peroxynitrous Acid; Pharmaceutical Services; Pharmacists; Pharmacy; Phaseolus; Phenotype; Phoeniceae; Phosphates; Phosphatidylinositol 3-Kinases; Phospholipid Transfer Proteins; Phospholipids; Phosphorus; Phosphorylation; Photoperiod; Photosynthesis; Phylogeny; Physical Endurance; Physicians; Pilot Projects; Piperidines; Pituitary Adenylate Cyclase-Activating Polypeptide; Plant Extracts; Plant Leaves; Plant Proteins; Plant Roots; Plaque, Atherosclerotic; Pneumonia; Pneumonia, Viral; Point-of-Care Testing; Polyethylene Glycols; Polymers; Polysorbates; Pore Forming Cytotoxic Proteins; Positron Emission Tomography Computed Tomography; Positron-Emission Tomography; Postprandial Period; Poverty; Pre-Exposure Prophylaxis; Prediabetic State; Predictive Value of Tests; Pregnancy; Pregnancy Trimester, First; Pregnancy, High-Risk; Prenatal Exposure Delayed Effects; Pressure; Prevalence; Primary Graft Dysfunction; Primary Health Care; Professional Role; Professionalism; Prognosis; Progression-Free Survival; Prolactin; Promoter Regions, Genetic; Proof of Concept Study; Proportional Hazards Models; Propylene Glycol; Prospective Studies; Prostate; Protein Binding; Protein Biosynthesis; Protein Isoforms; Protein Kinase Inhibitors; Protein Phosphatase 2; Protein Processing, Post-Translational; Protein Serine-Threonine Kinases; Protein Structure, Tertiary; Protein Transport; Proteoglycans; Proteome; Proto-Oncogene Proteins c-akt; Proto-Oncogene Proteins c-myc; Proto-Oncogene Proteins c-ret; Proto-Oncogene Proteins p21(ras); Proton Pumps; Protons; Protoporphyrins; Pseudomonas aeruginosa; Pseudomonas fluorescens; Pulmonary Artery; Pulmonary Disease, Chronic Obstructive; Pulmonary Gas Exchange; Pulmonary Veins; Pyrazoles; Pyridines; Pyrimidines; Qualitative Research; Quinoxalines; Rabbits; Random Allocation; Rats; Rats, Sprague-Dawley; Rats, Wistar; Receptors, Histamine H3; Receptors, Immunologic; Receptors, Transferrin; Recombinant Proteins; Recurrence; Reference Values; Referral and Consultation; Regional Blood Flow; Registries; Regulon; Renal Insufficiency, Chronic; Reperfusion Injury; Repressor Proteins; Reproducibility of Results; Republic of Korea; Research Design; Resistance Training; Respiration, Artificial; Respiratory Distress Syndrome; Respiratory Insufficiency; Resuscitation; Retinal Dehydrogenase; Retreatment; Retrospective Studies; Reverse Transcriptase Inhibitors; Rhinitis, Allergic; Ribosomal Proteins; Ribosomes; Risk Assessment; Risk Factors; Ritonavir; Rivers; RNA Interference; RNA-Seq; RNA, Messenger; RNA, Ribosomal, 16S; RNA, Small Interfering; Rosuvastatin Calcium; Rural Population; Saccharomyces cerevisiae; Saccharomyces cerevisiae Proteins; Salivary Ducts; Salivary Gland Neoplasms; San Francisco; SARS-CoV-2; Satiation; Satiety Response; Schools; Schools, Pharmacy; Seasons; Seawater; Selection, Genetic; Sequence Analysis, DNA; Serine-Threonine Kinase 3; Sewage; Sheep; Sheep, Domestic; Shock, Hemorrhagic; Signal Transduction; Silver; Silymarin; Single Photon Emission Computed Tomography Computed Tomography; Sirolimus; Sirtuin 1; Skin; Skin Neoplasms; Skin Physiological Phenomena; Sleep Initiation and Maintenance Disorders; Social Class; Social Participation; Social Support; Soil; Soil Microbiology; Solutions; Somatomedins; Soot; Specimen Handling; Spectrophotometry, Ultraviolet; Spectroscopy, Fourier Transform Infrared; Spectrum Analysis; Spinal Fractures; Spirometry; Staphylococcus aureus; STAT1 Transcription Factor; STAT3 Transcription Factor; Streptomyces coelicolor; Stress, Psychological; Stroke; Stroke Volume; Structure-Activity Relationship; Students, Medical; Students, Pharmacy; Substance Abuse Treatment Centers; Sulfur Dioxide; Surface Properties; Surface-Active Agents; Surveys and Questionnaires; Survival Analysis; Survival Rate; Survivin; Sweden; Swine; Swine, Miniature; Sympathetic Nervous System; T-Lymphocytes, Regulatory; Talaromyces; Tandem Mass Spectrometry; tau Proteins; Telemedicine; Telomerase; Telomere; Telomere Homeostasis; Temperature; Terminally Ill; Th1 Cells; Thiamethoxam; Thiazoles; Thiophenes; Thioredoxin Reductase 1; Thrombosis; Thulium; Thyroid Cancer, Papillary; Thyroid Carcinoma, Anaplastic; Thyroid Neoplasms; Time Factors; Titanium; Tomography, Emission-Computed, Single-Photon; Tomography, X-Ray Computed; TOR Serine-Threonine Kinases; Transcription Factor AP-1; Transcription Factors; Transcription, Genetic; Transcriptional Activation; Transcriptome; Transforming Growth Factor beta1; Transistors, Electronic; Translational Research, Biomedical; Transplantation Tolerance; Transplantation, Homologous; Transportation; Treatment Outcome; Tretinoin; Tuberculosis, Multidrug-Resistant; Tuberculosis, Pulmonary; Tubulin Modulators; Tumor Microenvironment; Tumor Necrosis Factor Inhibitors; Tumor Necrosis Factor-alpha; Twins; Ultrasonic Therapy; Ultrasonography; Ultraviolet Rays; United States; Up-Regulation; Uranium; Urethra; Urinary Bladder; Urodynamics; Uromodulin; Uveitis; Vasoconstrictor Agents; Ventricular Function, Left; Vero Cells; Vesicular Transport Proteins; Viral Nonstructural Proteins; Visual Acuity; Vital Capacity; Vitamin D; Vitamin D Deficiency; Vitamin K 2; Vitamins; Volatilization; Voriconazole; Waiting Lists; Waste Disposal, Fluid; Wastewater; Water Pollutants, Chemical; Whole Genome Sequencing; Wine; Wnt Signaling Pathway; Wound Healing; Wounds and Injuries; WW Domains; X-linked Nuclear Protein; X-Ray Diffraction; Xanthines; Xenograft Model Antitumor Assays; YAP-Signaling Proteins; Yogurt; Young Adult; Zebrafish; Zebrafish Proteins; Ziziphus

Several inflammatory markers such as cytokines, chemokines, and microRNAs (miRNAs) are well known to be induced during obesity and are strongly linked to their comorbidities. Among many others factors, the micronutrient status is suspected to reduce obesity-associated inflammation via blunting inflammatory signalling pathways. This is notably the case for active forms of vitamin A (all-trans retinoic acid ATRA) and vitamin D (1,25(OH)

Topics: Adipocytes; Animals; DNA Methylation; Humans; Mice; MicroRNAs; NF-kappa B; Obesity; Tretinoin

The prevalence of obesity continues to rise, underscoring the need to better understand the pathways mediating adipose tissue (AT) expansion. All-trans-retinoic acid (atRA), a bioactive vitamin A metabolite, regulates adipogenesis and energy metabolism, and, in rodent studies, aberrant vitamin A metabolism appears a key facet of metabolic dysregulation. The relevance of these findings to human disease is unknown, as are the specific enzymes implicated in vitamin A metabolism within human AT. We hypothesized that in human AT, family 1A aldehyde dehydrogenase (ALDH1A) enzymes contribute to atRA biosynthesis in a depot-specific manner. To test this hypothesis, parallel samples of subcutaneous and omental AT from participants (n = 15) were collected during elective abdominal surgeries to quantify atRA biosynthesis and key atRA synthesizing enzymes. ALDH1A1 was the most abundant ALDH1A isoform in both AT depots with expression approximately twofold higher in omental than subcutaneous AT. ALDH1A2 was detected only in omental AT. Formation velocity of atRA was approximately threefold higher (p = 0.0001) in omental AT (9.8 [7.6, 11.2]) pmol/min/mg) than subcutaneous AT (3.2 [2.1, 4.0] pmol/min/mg) and correlated with ALDH1A2 expression in omental AT (β-coefficient = 3.07, p = 0.0007) and with ALDH1A1 expression in subcutaneous AT (β-coefficient = 0.13, p = 0.003). Despite a positive correlation between body mass index (BMI) and omental ALDH1A1 protein expression (Spearman r = 0.65, p = 0.01), BMI did not correlate with atRA formation. Our findings suggest that ALDH1A2 is the primary mediator of atRA formation in omental AT, whereas ALDH1A1 is the principal atRA-synthesizing enzyme in subcutaneous AT. These data highlight AT depot as a critical variable for defining the roles of retinoids in human AT biology.

Topics: Adipose Tissue; Humans; Obesity; Subcutaneous Fat; Tretinoin; Vitamin A

Maternal obesity may compromise the micronutrient status of the offspring. Vitamin A (VA) is an essential micronutrient during neonatal development. Its active metabolite, retinoic acid (RA), is a key regulator of VA homeostasis, which also regulates adipose tissue (AT) development in obese adults. However, its role on VA status and AT metabolism in neonates was unknown and it was determined in the present study. Pregnant Sprague-Dawley rats were randomised to a normal fat diet (NFD) or a high fat diet (HFD). From postnatal day 5 (P5) to P20, half of the HFD pups received oral RA every 3 d (HFDRA group). NFD pups and the remaining HFD pups (HFD group) received placebo. Six hours after dosing on P8, P14 and P20,

Topics: Adipose Tissue; Animals; Animals, Newborn; Diet, High-Fat; Female; Humans; Micronutrients; Obesity; Obesity, Maternal; Pregnancy; Rats; Rats, Sprague-Dawley; Tretinoin; Vitamin A; Weight Gain

The β-carotene oxygenase 1 (BCO1) is the enzyme responsible for the cleavage of β-carotene to retinal, the first intermediate in vitamin A formation. Preclinical studies suggest that BCO1 expression is required for dietary β-carotene to affect lipid metabolism. The goal of this study was to generate a gene therapy strategy that over-expresses BCO1 in the adipose tissue and utilizes the β-carotene stored in adipocytes to produce vitamin A and reduce obesity.. We generated a novel adipose-tissue-specific, adeno-associated vector to over-express BCO1 (AT-AAV-BCO1) in murine adipocytes. We tested this vector using a unique model to achieve β-carotene accumulation in the adipose tissue, in which Bco1. AT-AAV-BCO1 infusions in the adipose tissue of the mice resulted in the production of retinoic acid, a vitamin A metabolite with strong effects on gene regulation. AT-AAV-BCO1 treatment also reduced adipose tissue size and adipocyte area by 35% and 30%, respectively. These effects were sex-specific, highlighting the complexity of vitamin A metabolism in mammals.. The over-expression of BCO1 through delivery of an AT-AAV-BCO1 leads to the conversion of β-carotene to vitamin A in adipocytes, which subsequently results in reduction of adiposity. These studies highlight for the first time the potential of adipose tissue β-carotene as a target for BCO1 over-expression in the reduction of obesity.

Topics: Adipocytes; Animals; beta Carotene; Female; Male; Mammals; Mice; Obesity; Tretinoin; Vitamin A

White rice and its unrefined form, brown rice, contain numerous compounds that are beneficial to human health. However, the starch content of rice can contribute to obesity, a main risk factor for nonalcoholic fatty liver disease (NAFLD).. We investigated the effect of rice consumption on NAFLD and its underlying molecular mechanism.. We randomly divided 7-week-old male obese Zucker (fa/fa) rats, an animal model of NAFLD, into 3 groups (n = 10 each) fed 1 of 3 diets for 10 weeks: a control diet (Cont; AIN-93G diet; 53% cornstarch), a white rice diet (WR; AIN-93G diet with cornstarch replaced with white rice powder), or a brown rice diet (BR; AIN-93G diet with cornstarch replaced with brown rice powder). Liver fat accumulation and gene expression related to lipid and vitamin A metabolisms, including retinoic acid (RA) signaling, were analyzed.. Hepatic lipid values were significantly decreased in the BR group compared with the Cont group, by 0.4-fold (P < 0.05). The expression of genes related to hepatic fatty acid oxidation, such as carnitine palmitoyltransferase 2, was approximately 2.1-fold higher in the BR group than the Cont group (P < 0.05). The expression of peroxisomal acyl-coenzyme A oxidase 1 and acyl-CoA dehydrogenase medium chain was also significantly increased, by 1.6-fold, in the BR group compared with the Cont group (P < 0.05). The expression of VLDL-secretion-related genes, such as microsomal triglyceride transfer protein, was also significantly higher in the BR group (2.4-fold; P < 0.05). Furthermore, aldehyde dehydrogenase 1 family member A1, an RA synthase gene, was 2-fold higher in the BR group than the Cont group (P < 0.05).. Brown rice prevented development of NAFLD in obese Zucker (fa/fa) rats. The beneficial effects of pregelatinized rice on NAFLD could be manifested as increased fatty acid oxidation and VLDL secretion, which are regulated by RA signaling.

Topics: Animals; Lipid Metabolism; Lipids; Liver; Male; Non-alcoholic Fatty Liver Disease; Obesity; Oryza; Rats; Rats, Zucker; Tretinoin

Topics: Adult; Biomarkers; Body Mass Index; Cardiometabolic Risk Factors; Carnitine O-Palmitoyltransferase; Cholesterol, HDL; Gene Expression; Healthy Volunteers; Humans; Leukocytes, Mononuclear; Lipid Metabolism; Male; Metabolic Syndrome; Obesity; Overweight; Real-Time Polymerase Chain Reaction; RNA, Messenger; Tretinoin

During muscle regeneration, excessive formation of adipogenic and fibrogenic tissues, from their respective fibro/adipogenic progenitors (FAPs), impairs functional recovery. Intrinsic mechanisms controlling the proliferation and differentiation of FAPs remain largely unexplored.. Here, we investigated the role of retinoic acid (RA) signalling in regulating FAPs and the subsequent effects on muscle restoration from a cardiotoxin-induced injury. Blockage of retinoic acid receptor (RAR) signalling was achieved through dominant negative retinoic acid receptor α (RARα403) expression specific in PDGFRα+ FAPs in vivo and by BMS493 treatment in vitro. Effects of RAR-signalling on FAP cellularity and muscle regeneration were also investigated in a high-fat diet-induced obese mice model.. Supplementation of RA increased the proliferation of FAPs during the early stages of regeneration while suppressing FAP differentiation and promoting apoptosis during the remodelling stage. Loss of RAR-signalling caused ectopic adipogenic differentiation of FAPs and impaired muscle regeneration. Furthermore, obesity disrupted the cellular transition of FAPs and attenuated muscle regeneration. Supplementation of RA to obese mice not only rescued impaired muscle fibre regeneration, but also inhibited infiltration of fat and fibrotic tissues during muscle repair. These beneficial effects were abolished after blocking RAR-signalling in FAPs of obese mice.. These data suggest that RAR-signalling in FAPs is a critical therapeutic target for suppressing differentiation of FAPs and facilitating the regeneration of muscle and other tissues.. This study was supported by grants from the National Institutes of Health (R01-HD067449 and R21-AG049976) to M.D.

Topics: Adipogenesis; Animals; Cell Differentiation; Fibrosis; Immunohistochemistry; Male; Mesenchymal Stem Cells; Mice; Mice, Transgenic; Muscle, Skeletal; Obesity; Regeneration; Signal Transduction; Tretinoin

Dietary obesity is regarded as a problem worldwide, and it has been revealed the strong linkage between obesity and allergic inflammation. Fatty acid-binding protein 5 (FABP5) is expressed in lung cells, such as alveolar epithelial cells (ECs) and alveolar macrophages, and plays an important role in infectious lung inflammation. However, we do not know precise mechanisms on how lipid metabolic change in the lung affects allergic lung inflammation. In this study, we showed that Fabp5

Topics: Alveolar Epithelial Cells; Animals; Asthma; Diet, High-Fat; Disease Models, Animal; Fatty Acid-Binding Proteins; Gene Expression; Inflammation; Interleukin-1 Receptor-Like 1 Protein; Lipid Metabolism; Lung; Lymphocytes; Mice, Inbred C57BL; Molecular Targeted Therapy; Neoplasm Proteins; Obesity; Tretinoin

It has been shown that adipogenesis can be modulated by factors such as all-trans retinoic acid (ATRA) and calcium.. To determine, the combined effect of ATRA and calcium on the differentiation of human adipose-derived stem cells (hADSCs).. Mesenchymal stem cells (MSCs) were differentiated into the adipocytes by 0.5 and 1 µM of ATRA and 5 and 10 mM calcium separately or in combination. After MTS assay the differentiation of MSCs to adipocyte was evaluated, Oil Red O staining, GLUT4 concentration and gene expression of PPARG2, adiponectin, and GLUT4 were measured by Real-Time PCR.. Except 10 mM calcium treated group, other groups and more significantly combination treatments could reduce all adipocyte markers compared to the control.. These results suggest that ATRA and calcium together have significant inhibitory effect on adipogenesis that can be helpful for finding new mechanisms to prevent or control the adipogenesis.

Topics: Adipogenesis; Adiponectin; Adult; Adult Stem Cells; Biomarkers; Calcium Signaling; Cells, Cultured; Down-Regulation; Female; Gene Expression Profiling; Gene Expression Regulation, Developmental; Glucose Transporter Type 4; Humans; Kinetics; Lipectomy; Obesity; PPAR gamma; Subcutaneous Fat, Abdominal; Tretinoin; Triglycerides

Chronic inflammation underlies the development of metabolic diseases and individuals with metabolic disease often also suffer from delayed wound healing due to prolonged inflammation. Resolving inflammation provides a therapeutic strategy in treating metabolic diseases. We previously showed that during an anti-inflammatory response when macrophages were alternatively (M2) polarized, retinoic acid (RA) dramatically activated arginase 1 gene (Arg1), a gene crucial for wound healing. Here we report that a widely used sulfonylurea drug for type 2 diabetes mellitus (T2DM), glyburide, enhances the anti-inflammatory response and synergizes with RA to promote wound healing. Our data also delineate the mechanism underlying glyburide's anti-inflammatory effect, which is to stimulate the degradation of a pro-inflammatory regulator, Receptor Interacting Protein 140 (RIP140), by activating Ca2+/calmodulin-dependent protein kinase II (CamKII) that triggers specific ubiquitination of RIP140 for degradation. By stimulating RIP140 degradation, glyburide enhances M2 polarization and anti-inflammation. Using a high-fat diet induced obesity mouse model to monitor wound healing effects, we provide a proof-of-concept for a therapeutic strategy that combining glyburide and RA can significantly improve wound healing. Mechanistically, this study uncovers a new mechanism of action of glyburide and a new pathway modulating RIP140 protein degradation that is mediated by CamKII signaling.

Topics: Animals; Calcium-Calmodulin-Dependent Protein Kinase Type 2; Cells, Cultured; Diet, High-Fat; Drug Synergism; Glyburide; Macrophages, Peritoneal; Male; Mice; Mice, Inbred C57BL; Nuclear Receptor Co-Repressor 1; Obesity; Phosphorylation; RAW 264.7 Cells; Signal Transduction; Tretinoin; Ubiquitination; Wound Healing

Impaired adipogenesis may be the underlying cause in the development of obesity and type II diabetes. Mechanistically, the family of Homeobox transcription factors is implicated in the regulation of adipocyte fate. Hoxa5 is highly expressed in adipocytes, and its mRNA expression is decreased during differentiation. However, the function of Hoxa5 in adipose tissue has been poorly understood. The aim of this study is to unveil the role of Hoxa5 on adipocyte differentiation and its underlying mechanisms.. Quantitative real-time PCR (qPCR) and western blot were performed to determine Hoxa5 expression in primary adipocytes and in adipose tissues from mice. Lipid accumulation was evaluated by bodipy staining. Dual luciferase assay was applied to explore the transcription factor of Hoxa5 and the transcriptional target gene modulated by Hoxa5. All measurements were performed at least for three times at least.. A significant reduction of Hoxa5 expression was observed in adipose tissue of High Fat Diet (HFD) induced obesity mice. We determined Hoxa5 increased adipocytes differentiation and mitochondrial biogenesis in adipocytes in vitro. CEBPβ was determined a transcription factor of Hoxa5 and inhibited methylation level of Hoxa5 by combining on the promoter of Hoxa5. Importantly, we found Fabp4, a known positive regulator of adipocytes differentiation, was transcriptional activation by Hoxa5. In addition, Hoxa5 promotes adipocytes differentiation by inhibiting PKA/HSL pathway.. Our study demonstrated the promoting role of Hoxa5 in adipocytes differentiation and therefore bringing a new therapeutic mean to the treatment of obesity and type II diabetes.

Topics: Adipogenesis; Adipose Tissue; Animals; CCAAT-Enhancer-Binding Protein-beta; Cell Differentiation; Cells, Cultured; Cyclic AMP-Dependent Protein Kinases; Diet, High-Fat; DNA Methylation; DNA, Mitochondrial; fas Receptor; Fatty Acid-Binding Proteins; Homeodomain Proteins; Male; Mice; Obesity; Phosphoproteins; PPAR gamma; Signal Transduction; Sterol Esterase; Transcription Factors; Tretinoin

The impact of unrhythmic circadian clock on obesity has started to be increasingly appreciated nowadays. Recently it was discovered that interaction between intestinal microbiota and unrhythmic circadian clock plays a key role in such a process. It involves relaying signals from microbiota through dendritic cells to group 3 innate lymphoid cells in the intestine and in the end impacting some of the key transcription factors of circadian clock. Breaking such a signal relay may prove to be an effective way reducing unrhythmic circadian clock-induced obesity. Here, we propose a hypothesis and design experiments to prove that suppressing one of the transcription factors, RUNX1, plays a key role in the homing of ILC3 cells to intestine. Such suppression is in response to a retinoic acid-RARα binding initiated pathway and results in the upregulation of gut-homing chemokine receptor CCR9 and downregulation of lymphoid tissue-homing receptor CCR7, which can then guide ILC3 cells to intestine. Therapies that can specifically sustain Runx1 expression in ILC3 cells may assist preventing the ever-escalating obesity problem in modern society.

Topics: Animals; Cell Separation; Circadian Clocks; Circadian Rhythm; Core Binding Factor Alpha 2 Subunit; Dendritic Cells; Flow Cytometry; Gastrointestinal Microbiome; Humans; Immunity, Innate; Intestinal Mucosa; Lymphocytes; Lymphoid Tissue; Mice; Obesity; Tretinoin

Maternal vitamin A intake varies but its impact on offspring metabolic health is unknown. Here we found that maternal vitamin A or retinoic acid (RA) administration expanded PDGFRα

Topics: Adipogenesis; Adipose Tissue, Beige; Animals; Body Temperature; Cells, Cultured; Chromatography, High Pressure Liquid; Diet, High-Fat; Dietary Supplements; Female; Glucose Tolerance Test; Male; Mice; Mice, Inbred C57BL; Obesity; Oxygen Consumption; Pregnancy; Receptor, Platelet-Derived Growth Factor alpha; Retinaldehyde; Signal Transduction; Stromal Cells; Tretinoin; Vascular Endothelial Growth Factor A; Vitamin A

Retinoic acid (RA), a bioactive metabolite of vitamin A, is a critical mediator of cell differentiation. RA blocks adipogenesis, but mechanisms remain to be established. ZFP423 is a key transcription factor maintaining white adipose identity. We found that RA inhibits Zfp423 expression and adipogenesis via blocking DNA demethylation in the promoter of Zfp423, a process mediated by growth arrest and DNA-damage-inducible protein alpha (GADD45A). RA induces the partnering between retinoic acid receptor (RAR) and tumor suppressor inhibitor of growth protein 1 (ING1), which prevents the formation of GADD45A and ING1 complex necessary for locus-specific Zfp423 DNA demethylation. In vivo, vitamin A supplementation prevents obesity, downregulates Gadd45a expression, and reduces GADD45A binding and DNA demethylation in the Zfp423 promoter. Inhibition of Zfp423 expression due to RA contributes to the enhanced brown adipogenesis. In summary, RA inhibits white adipogenesis by inducing RAR and ING1 interaction and inhibiting Gadd45a expression, which prevents GADD45A-mediated DNA demethylation.

Topics: 3T3-L1 Cells; Adipogenesis; Animals; Cell Cycle Proteins; Cell Line; Diet, High-Fat; DNA Demethylation; DNA-Binding Proteins; Down-Regulation; Male; Mice; Mice, Inbred C57BL; Nuclear Proteins; Obesity; Promoter Regions, Genetic; Protein Interaction Maps; Transcription Factors; Tretinoin

Adiponectin is an adipocyte-derived adipokine with potent antidiabetic, anti-inflammatory, and antiatherogenic activity. Long-term, high-fat diet results in gain of body weight, adiposity, further inflammatory-based cardiovascular diseases, and reduced adiponectin secretion. Vitamin A derivatives/retinoids are involved in several of these processes, which mainly take place in white adipose tissue (WAT). In this study, we examined adiponectin expression as a function of dietary high-fat and high-vitamin A conditions in mice. A decrease of adiponectin expression in addition to an up-regulation of aldehyde dehydrogenase A1 (ALDH1A1), retinoid signaling, and retinoic acid response element signaling was selectively observed in WAT of mice fed a normal-vitamin A, high-fat diet. Reduced adiponectin expression in WAT was also observed in mice fed a high-vitamin A diet. Adipocyte cell culture revealed that endogenous and synthetic retinoic acid receptor (RAR)α- and RARγ-selective agonists, as well as a synthetic retinoid X receptor agonist, efficiently reduced adiponectin expression, whereas ALDH1A1 expression only increased with RAR agonists. We conclude that reduced adiponectin expression under high-fat dietary conditions is dependent on 1) increased ALDH1A1 expression in adipocytes, which does not increase all-trans-retinoic acid levels; 2) further RAR ligand-induced, WAT-selective, increased retinoic acid response element-mediated signaling; and 3) RAR ligand-dependent reduction of adiponectin expression.-Landrier, J.-F., Kasiri, E., Karkeni, E., Mihály, J., Béke, G., Weiss, K., Lucas, R., Aydemir, G., Salles, J., Walrand, S., de Lera, A. R., Rühl, R. Reduced adiponectin expression after high-fat diet is associated with selective up-regulation of ALDH1A1 and further retinoic acid receptor signaling in adipose tissue.

Topics: 3T3-L1 Cells; Adipocytes; Adiponectin; Adipose Tissue; Aldehyde Dehydrogenase; Aldehyde Dehydrogenase 1 Family; Alkaloids; Animal Feed; Animals; Diet, High-Fat; Dietary Supplements; Down-Regulation; Gene Expression Regulation; Male; Mice; Mice, Knockout; Obesity; Oxindoles; Receptors, Retinoic Acid; Retinal Dehydrogenase; Signal Transduction; Tretinoin; Up-Regulation; Vitamin A

We have recently characterized the role of lipocalin 2 (Lcn2) as a new adipose-derived cytokine in the regulation of adaptive thermogenesis via a non-adrenergic pathway. Herein, we explored a potential non-adrenergic mechanism by which Lcn2 regulates thermogenesis and lipid metabolism. We found that Lcn2 is a retinoic acid target gene, and retinoic acid concurrently stimulated UCP1 and Lcn2 expression in adipocytes. Lcn2 KO mice exhibited a blunted effect of all-trans-retinoic acid (ATRA) on body weight and fat mass, lipid metabolism, and retinoic acid signaling pathway activation in adipose tissue under the high fat diet-induced obese condition. We further demonstrated that Lcn2 is required for the full action of ATRA on the induction of UCP1 and PGC-1α expression in brown adipocytes and the restoration of cold intolerance in Lcn2 KO mice. Interestingly, we discovered that Lcn2 KO mice have decreased levels of retinoic acid and retinol in adipose tissue. The protein levels of STRA6 responsible for retinol uptake were significantly decreased in adipose tissue. The retinol transporter RBP4 was increased in adipose tissue but decreased in the circulation, suggesting the impairment of RBP4 secretion in Lcn2 KO adipose tissue. Moreover, Lcn2 deficiency abolished the ATRA effect on RBP4 expression in adipocytes. All the data suggest that the decreased retinoid level and action are associated with impaired retinol transport and storage in adipose tissue in Lcn2 KO mice. We conclude that Lcn2 plays a critical role in regulating metabolic homeostasis of retinoids and retinoid-mediated thermogenesis in adipose tissue.

Topics: Adipocytes, Brown; Adipocytes, White; Adipose Tissue; Animals; Homeostasis; Lipocalin-2; Male; Membrane Proteins; Mice; Mice, Knockout; Obesity; Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; Protein Binding; Retinoids; Retinol-Binding Proteins, Plasma; Thermogenesis; Tretinoin; Uncoupling Protein 1

In hypertensive rodents, retinoic acid (RA) prevents adverse cardiac remodelling and improves myocardial infarction outcome, but its role in obesity-related changes of cardiac tissue are unclear. We hypothesized that all-trans RA (ATRA) treatment will improve the cardioprotective oxytocin-natriuretic peptides (OT-NP) system, preventing apoptosis and collagen accumulation in hearts of ob/ob mice, a mouse model of obesity and insulin resistance. Female 9-week-old B6.V-Lep/J ob/ob mice (n = 16) were divided into 2 groups: 1 group (n = 8) treated with 100 μg of ATRA dissolved in 100 μL of corn oil (vehicle) delivered daily (∼2 μg·g body weight(-1)·day(-1)) by stomach intubation for 16 days, and 1 group (n = 8) that received the vehicle alone. A group of nonobese littermate mice (n = 9) served as controls. Ob/ob mice exhibited obesity, hyperglycaemia, and downregulation of the cardiac OT-NP system, including the mRNA for the transcription factor GATA4, OT receptor and brain NP, and the protein expression for endothelial nitric oxide synthase. Hearts from ob/ob mice also demonstrated increased apoptosis and collagen accumulation. ATRA treatment induced weight loss and decreased adipocytes diameter in the visceral fat, thus reducing visceral obesity, which is associated with a high risk for cardiovascular disease. RA treatment was associated with a reduction in hyperglycemia and a normalization of the OT-NP system's expression in the hearts of ob/ob mice. Furthermore, ATRA treatment prevented apoptosis and collagen accumulation in hearts of ob/ob mice. The present study indicates that ATRA treatment was effective in restoring the cardioprotective OT-NP system and in preventing abnormal cardiac remodelling in the ob/ob mice.

Topics: Animals; Apoptosis; Female; Fibrosis; Gene Expression Regulation; Mice; Mice, Obese; Myocytes, Cardiac; Natriuretic Peptides; Obesity; Tretinoin

Obesity produces a chronic inflammatory state that contributes to the development of diabetes and atherosclerosis. In obese humans, fat depot adipocytes and macrophages produce inflammatory cytokines and other factors which exert unfavorable local and systemic immune responses. The expression of many cytokines is modulated at the post-transcriptional level by mRNA-binding proteins which recognize AU-rich elements (AREs) in the 3'-untranslated regions (3'-UTR) of these transcripts. One such protein, zinc finger protein 36 (Zfp36), is known to destabilize target mRNAs leading to decreased cytokine expression. Few regulators of Zfp36 expression in adipocytes have been described and mRNA targets of Zfp36 in adipocytes are largely unknown. We found that macrophage-derived inflammatory stimuli enhanced endogenous Zfp36 expression in 3T3-L1 adipocytes. Furthermore, the β-adrenergic receptor agonist isoproterenol (Iso) and the glucocorticoid dexamethasone (Dex) each enhanced Zfp36 expression in adipocytes, the former most likely via a cyclic adenosine monophosphate (cAMP)-dependent pathway. By contrast, Zfp36 expression in murine macrophages (RAW 264.7) was not enhanced by exposure to Dex but was stimulated by retinoic acid (RA). Zfp36 inhibited basal and lipopolysaccharide (LPS)-stimulated interleukin-6 (IL-6) expression in adipocytes. These data reveal important and cell type-specific modulators of Zfp36 expression in adipocytes and macrophages and identify Zfp36 as a potent repressor of adipocyte-derived IL-6. Furthermore, this work identifies new factors that stimulate adipocyte Zfp36 expression that are neither classically inflammatory nor mitogenic. Upregulating an mRNA-binding protein for therapeutic purposes may provide a novel mechanistic approach with which to treat diverse inflammatory disorders including common conditions associated with obesity.

Topics: 3T3-L1 Cells; Adipocytes; Animals; Colforsin; Gene Expression Regulation; Humans; Interleukin-6; Macrophages; Mice; Obesity; Receptors, Adrenergic, beta; RNA, Messenger; Signal Transduction; Tretinoin; Tristetraprolin; Tumor Necrosis Factor-alpha; Up-Regulation

We investigated whether body mass index (BMI) correlates with distinct outcomes in newly diagnosed acute promyelocytic leukemia (APL). The study population included 144 patients with newly diagnosed and genetically confirmed APL consecutively treated at a single institution. All patients received All-trans retinoic acid and idarubicin according to the GIMEMA protocols AIDA-0493 and AIDA-2000. Outcome estimates according to the BMI were carried out together with multivariable analysis for the risk of relapse and differentiation syndrome. Fifty-four (37.5%) were under/normal weight (BMI < 25), whereas 90 (62.5%) patients were overweight/obese (BMI ≥ 25). An increased BMI was associated with older age (P < .0001) and male sex (P = .02). BMI was the most powerful predictor of differentiation syndrome in multivariable analysis (odds ratio = 7.24; 95% CI, 1.50-34; P = .014). After a median follow-up of 6 years, the estimated cumulative incidence of relapse at 5 years was 31.6% (95% CI, 22.7%-43.8%) in overweight/obese and 11.2% (95% CI, 5.3%-23.8%) in underweight/normal weight patients (P = .029). Multivariable analysis showed that BMI was an independent predictor of relapse (hazard ratio = 2.45, 95% CI, 1.00-5.99, in overweight/obese vs under/normal weight patients, P = .049). An increased BMI at diagnosis is associated with a higher risk of developing differentiation syndrome and disease relapse in APL patients treated with AIDA protocols.

Topics: Adolescent; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Body Mass Index; Child; Child, Preschool; Female; Follow-Up Studies; Humans; Idarubicin; Infant; Infant, Newborn; Leukemia, Promyelocytic, Acute; Male; Middle Aged; Neoplasm Recurrence, Local; Obesity; Overweight; Prognosis; Risk Factors; Survival Rate; Syndrome; Tretinoin; Young Adult

Retinoic acid (RA) protects mice from diet-induced obesity. The activity is mediated in part through activation of the nuclear receptors RA receptors (RARs) and peroxisome proliferator-activated receptor β/δ and their associated binding proteins cellular RA binding protein type II (CRABP-II) and fatty acid binding protein type 5 in adipocytes and skeletal muscle, leading to enhanced lipid oxidation and energy dissipation. It was also reported that RA inhibits differentiation of cultured preadipocytes. However, whether the hormone suppresses adipogenesis in vivo and how the activity is propagated remained unknown. In this study, we show that RA inhibits adipocyte differentiation by activating the CRABP-II/RARγ path in preadipose cells, thereby upregulating the expression of the adipogenesis inhibitors Pref-1, Sox9, and Kruppel-like factor 2 (KLF2). In turn, KLF2 induces the expression of CRABP-II and RARγ, further potentiating inhibition of adipocyte differentiation by RA. The data also indicate that RA suppresses adipogenesis in vivo and that the activity significantly contributes to the ability of the hormone to counteract diet-induced obesity.

Topics: Adipocytes; Adipogenesis; Animals; Cells, Cultured; Diet; Dietary Fats; Flow Cytometry; Humans; Kruppel-Like Transcription Factors; Mice; Mice, Inbred C57BL; Obesity; Receptors, Retinoic Acid; Retinoic Acid Receptor gamma; Signal Transduction; Tretinoin; Up-Regulation

The roles of vitamin A (VA) in the development of metabolic diseases remain unanswered. We have reported that retinoids synergized with insulin to induce the expression of sterol-regulatory element-binding protein 1c gene (Srebp-1c) expression in primary rat hepatocytes. Additionally, the hepatic Srebp-1c expression is elevated in Zucker fatty (ZF) rats, and reduced in those fed a VA deficient diet. VA is metabolized to retinoic acid (RA) for regulating gene expression. We hypothesized that the expression of RA production enzymes contributes to the regulation of the hepatic Srebp-1c expression. Therefore, we analyzed their expression levels in Zucker lean (ZL) and ZF rats. The mRNA levels of retinaldehyde dehydrogenase family 1 gene (Raldh1) were found to be higher in the isolated and cultured primary hepatocytes from ZF rats than that from ZL rats. The RALDH1 protein level was elevated in the liver of ZF rats. Retinol and retinal dose- and time-dependently induced the expression of RA responsive Cyp26a1 gene in hepatocytes and hepatoma cells. INS-1 cells were identified as an ideal tool to study the effects of RA production on the regulation of gene expression because only RA, but not retinal, induced Srebp-1c mRNA expression in them. Recombinant adenovirus containing rat Raldh1 cDNA was made and used to infect INS-1 cells. The over-expression of RALDH1 introduced the retinal-mediated induction of Srebp-1c expression in INS-1 cells. We conclude that the expression levels of the enzymes for RA production may contribute to the regulation of RA responsive genes, and determine the responses of the cells to retinoid treatments. The elevated hepatic expression of Raldh1 in ZF rats may cause the excessive RA production from retinol, and in turn, result in higher Srebp-1c expression. This excessive RA production may be one of the factors contributing to the elevated lipogenesis in the liver of ZF rats.

Topics: Aldehyde Dehydrogenase 1 Family; Animals; Cell Line; Cytochrome P-450 Enzyme System; Gene Expression Regulation; Hepatocytes; Lipogenesis; Liver; Male; Obesity; Rats; Rats, Zucker; Retinal Dehydrogenase; Retinaldehyde; Retinoic Acid 4-Hydroxylase; RNA, Messenger; Signal Transduction; Sterol Regulatory Element Binding Protein 1; Tretinoin; Vitamin A

Obesity and the related metabolic abnormalities are associated with increased risk of hepatocellular carcinoma (HCC). Malfunctioning of retinoid X receptor (RXR) α due to phosphorylation by Ras/MAPK also plays a critical role in liver carcinogenesis. In the present study, we examined the effects of acyclic retinoid (ACR), which targets RXRα, on the development of diethylnitrosamine (DEN)-induced liver tumorigenesis in C57BLKS/J- +Lepr(db)/+Lepr(db) (db/db) obese mice. Male db/db mice were given tap water containing 40 ppm DEN for 2 weeks, after which they were fed a diet containing 0.03% or 0.06% of ACR throughout the experiment. In mice treated with either dose of ACR for 34 weeks, the development of liver cell adenomas was significantly inhibited as compared with basal diet-fed mice. ACR markedly inhibited the activation of Ras and phosphorylation of the ERK (extracellular signal-regulated kinase) and RXRα proteins in the livers of experimental mice. It also increased the expression of RAR β and p21(CIP1) mRNA while decreasing the expression of cyclin D1, c-Fos, and c-Jun mRNA in the liver, thereby restoring RXRα function. Administration of ACR improved liver steatosis and activated the AMPK protein. The serum levels of insulin decreased by ACR treatment, whereas the quantitative insulin sensitivity check index (QUICKI) values increased, indicating improved insulin sensitivity. The serum levels of TNF-α and the expression levels of TNF- α, IL-6, and IL-1 β mRNA in the livers of DEN-treated db/db mice were decreased by ACR treatment, suggesting attenuation of the chronic inflammation induced by excessive fatty deposits. ACR may be, therefore, useful in the chemoprevention of obesity-related HCC.

Topics: Animals; Antineoplastic Agents; Blotting, Western; Cytokines; Diabetes Complications; Diabetes Mellitus; Diethylnitrosamine; Insulin Resistance; Liver Neoplasms, Experimental; Male; Mice; Mice, Inbred C57BL; Mice, Obese; Obesity; Phosphorylation; ras Proteins; Receptors, Leptin; Retinoid X Receptor alpha; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; STAT3 Transcription Factor; Tretinoin

We previously reported that mice with skin-specific deletion of stearoyl-CoA desaturase-1 (Scd1) recapitulated the skin phenotype and hypermetabolism observed in mice with a whole-body deletion of Scd1. In this study, we first performed a diet-induced obesity experiment at thermoneutral temperature (33°C) and found that skin-specific Scd1 knockout (SKO) mice still remain resistant to obesity. To elucidate the metabolic changes in the skin that contribute to the obesity resistance and skin phenotype, we performed microarray analysis of skin gene expression in male SKO and control mice fed a standard rodent diet. We identified an extraordinary number of differentially expressed genes that support the previously documented histological observations of sebaceous gland hypoplasia, inflammation and epidermal hyperplasia in SKO mice. Additionally, transcript levels were reduced in skin of SKO mice for genes involved in fatty acid synthesis, elongation and desaturation, which may be attributed to decreased abundance of key transcription factors including SREBP1c, ChREBP and LXRα. Conversely, genes involved in cholesterol synthesis were increased, suggesting an imbalance between skin fatty acid and cholesterol synthesis. Unexpectedly, we observed a robust elevation in skin retinol, retinoic acid and retinoic acid-induced genes in SKO mice. Furthermore, SEB-1 sebocytes treated with retinol and SCD inhibitor also display an elevation in retinoic acid-induced genes. These results highlight the importance of monounsaturated fatty acid synthesis for maintaining retinol homeostasis and point to disturbed retinol metabolism as a novel contributor to the Scd1 deficiency-induced skin phenotype.

Topics: Acute-Phase Proteins; Animals; Epidermis; Fatty Acids; Gene Expression Profiling; Hair; Hyperplasia; Inflammation; Lipocalin-2; Lipocalins; Male; Mice; Mice, Knockout; Obesity; Oligonucleotide Array Sequence Analysis; Oncogene Proteins; PPAR delta; Receptors, Retinoic Acid; Sebaceous Glands; Skin; Stearoyl-CoA Desaturase; Sterols; Temperature; Transcription Factors; Transcriptional Activation; Tretinoin; Vitamin A

Increased adipocyte formation from mesenchymal stem cells (MSCs) is typical for obesity. It is recently observed that bone morphogenetic proteins (BMPs) provide instructive signals for the commitment of MSCs to adipocytes. We examined potential role of retinoic acid (RA) in inhibiting the BMP4 induction of MSC commitment toward adipocyte. BMP4-treated C3H10T1/2 MSCs, when further exposed to adipogenic differentiation media, displayed distinct adipocytic commitment and differentiation. This could be inhibited by RA exposure during the BMP4 treatment stage (commitment stage before adipogenic hormonal inducers were given), as was observed by reductions in key adipogenic genes/transcription factors (C/EBPα, PPARγ, aP2), lipogenic genes (LPL, FAS, GLUT4), and lipid accumulation. Among RA receptors (RARs) screened, RARβ was mainly upregulated under RA exposure. BMP4 signaled through both Smad1/5/8 and p38 mitogen-activated protein kinase (MAPK) and RA significantly suppressed the BMP4-triggered phosphorylation of both Smad1/5/8 and p38MAPK. These data suggest that RA has inhibitory effects on the BMP4 induction of C3H10T1/2 adipocytic commitment via downregulating Smad/p38MAPK signaling. How to inhibit MSC adipocytic commitment, as partly revealed in this study, will have a significant impact on treating obesity and related diseases.

Topics: Adipocytes; Adipogenesis; Animals; Bone Morphogenetic Protein 4; Cell Line; Culture Media; Down-Regulation; Mesenchymal Stem Cells; Mice; Obesity; p38 Mitogen-Activated Protein Kinases; Smad Proteins; Tretinoin

Apo-10'-lycopenoic acid (apo-10-lycac), a metabolite of lycopene, has been shown to possess potent biological activities, notably via the retinoic acid receptors (RAR). In the current study, its impact on adipose tissue and adipocytes was studied. In microarray experiments, the set of genes regulated by apo-10-lycac treatments was compared to the set of genes regulated by all-trans retinoic acid (ATRA), the natural ligand of RAR, in adipocytes. Approximately 27.5% of the genes regulated by apo-10-lycac treatments were also regulated by ATRA, suggesting a common ability in terms of gene expression modulation, possibly via RAR transactivation. The physiological impact of apo-10-lycac on adipose tissue biology was evaluated. If it had no effect on adipogenesis in the 3T3-L1 cell model, this metabolite may have a preventative effect against inflammation, by preventing the increase in the inflammatory markers, interleukin 6 and interleukin 1β in various dedicated models. The ability of apo-10-lycac to transactivate the RAR and to modulate the transcription of RAR target gene was brought in vivo in adipose tissue. While apo-10-lycac was not detected in adipose tissue, a metabolite with a molecular weight with 2Da larger mass was detected, suggesting that a dihydro-apo-10'-lycopenoic acid, may be present in adipose tissue and that this compound could active or may lead to further active RAR-activating apo-10-lycac metabolites. Since apo-10-lycac treatments induce anti-inflammatory effects in adipose tissue but do not inhibit adipogenesis, we propose that apo-10-lycac treatments and its potential active metabolites in WAT may be considered for prevention strategies relevant for obesity-associated pathologies.

Topics: 3T3-L1 Cells; Adipocytes; Adipose Tissue; Animals; Carotenoids; Fatty Acids, Unsaturated; Gene Expression Profiling; Genes, Reporter; Inflammation; Interleukin-1beta; Interleukin-6; Male; Mice; Mice, Inbred C57BL; Obesity; Oligonucleotide Array Sequence Analysis; Real-Time Polymerase Chain Reaction; Receptors, Retinoic Acid; RNA, Messenger; Tissue Culture Techniques; Transcriptional Activation; Tretinoin

The pseudokinase tribbles homologue 3 (Drosophila) (TRIB3) negatively interferes with insulin-mediated phosphorylation and activation of v-akt murine thymoma viral oncogene homologue 1 (AKT1, also known as protein kinase B). Animal studies have shown that Trib3 expression was higher in the fasting state and in animal models of diabetes, promoting hyperglycaemia presumably by increasing glucose production in the liver. Less is known about the role of TRIB3 in insulin resistance in humans, although a gain-of-function mutation associated with abnormalities related to insulin resistance has been described in TRIB3.. We determined hepatic mRNA expression of TRIB3 and selected genes encoding enzymes, transcription factors and coactivators involved in glucose homeostasis. We also determined biochemical variables of intermediary metabolism in obese patients with varying degrees of insulin resistance.. In our study population hepatic TRIB3 mRNA expression was associated with surrogate markers of insulin resistance. TRIB3 expression was significantly increased in a subgroup with high HOMA of insulin resistance (HOMA-IR) compared with a low HOMA-IR group (p = 0.0033). TRIB3 transcript levels were correlated with PEPCK (also known as PCK2) mRNA expression (p = 0.0014) and mRNA expression of PPARGC1A (p = 0.0020), PPARGC1B (p < 0.0001), USF1 (p = 0.0017), FOXO1 (p = 0.0003) and SREBP-1c (also known as SREBF1; p = 0.0360). Furthermore ligands of peroxisome proliferator-activated receptor alpha/retinoid X receptor and overexpression of its coactivator PPARGC1A as well as overexpression of SREBP-1c and its coactivator PPARGC1B increased TRIB3 promoter activity in HepG2 cells.. We have found evidence for a role of aberrant hepatic TRIB3 transcript levels in insulin resistance in obese humans and identified potential transcriptional pathways involved in regulation of TRIB3 gene expression in the liver.

Topics: Carrier Proteins; Cell Cycle Proteins; Gene Expression; Heat-Shock Proteins; Hep G2 Cells; Humans; Insulin Resistance; Liver; Obesity; Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; PPAR alpha; Protein Serine-Threonine Kinases; Pyrimidines; Repressor Proteins; RNA-Binding Proteins; RNA, Messenger; Sterol Regulatory Element Binding Protein 1; Transcription Factors; Tretinoin

Many biological activities of all-trans-retinoic acid (RA) are mediated by the ligand-activated transcription factors termed retinoic acid receptors (RARs), but this hormone can also activate the nuclear receptor peroxisome proliferation-activated receptor beta/delta (PPARbeta/delta). We show here that adipocyte differentiation is accompanied by a shift in RA signaling which, in mature adipocytes, allows RA to activate both RARs and PPARbeta/delta, thereby enhancing lipolysis and depleting lipid stores. In vivo studies using a dietary-induced mouse model of obesity indicated that onset of obesity is accompanied by downregulation of adipose PPARbeta/delta expression and activity. RA treatment of obese mice induced expression of PPARbeta/delta and RAR target genes involved in regulation of lipid homeostasis, leading to weight loss and improved insulin responsiveness. RA treatment also restored adipose PPARbeta/delta expression. The data indicate that suppression of obesity and insulin resistance by RA is largely mediated by PPARbeta/delta and is further enhanced by activation of RARs. By targeting two nuclear receptors, RA may be a uniquely efficacious agent in the therapy and prevention of the metabolic syndrome.

Topics: 3T3-L1 Cells; Adipocytes; Adipogenesis; Adiposity; Animals; Cell Differentiation; Diet; Disease Models, Animal; Fatty Acid-Binding Proteins; Insulin Resistance; Lipolysis; Mice; Mice, Inbred C57BL; Neoplasm Proteins; Obesity; PPAR delta; PPAR-beta; Receptors, Retinoic Acid; Signal Transduction; Tretinoin

Topics: Acetazolamide; Adult; Anticonvulsants; Antineoplastic Agents; Female; Humans; Idarubicin; Leukemia, Promyelocytic, Acute; Obesity; Pseudotumor Cerebri; Spinal Puncture; Tretinoin

Acanthosis nigricans (AN) is a cutaneous marker of various underlying systemic conditions. To date, no satisfactory topical therapy for this cutaneous disorder has been described. The following is a report of the successful use of a combination of 12% ammonium lactate cream and 0.05% tretinoin cream to treat AN associated with obesity.

Topics: Acanthosis Nigricans; Administration, Topical; Adolescent; Drug Therapy, Combination; Humans; Keratolytic Agents; Lactic Acid; Male; Obesity; Quaternary Ammonium Compounds; Tretinoin

Circulating adiponectin levels fall whereas leptin levels rise with obesity, suggesting that regulation of these two adipocyte-derived hormones may be simultaneously influenced by common obesity-related factors. We examined adiponectin mRNA levels in WAT and in some instances, brown adipose tissue (BAT) following fasting and refeeding, acute and chronic administration of a beta(3)-adrenergic agonist, acute treatment with retinoic acid (RA) and a glucocorticoid, and following chronic infusion of leptin and compared the expression of adiponectin to that of leptin in each circumstance. Serum concentrations of adiponectin were also reported for most of the treatments. Fasting diminished and refeeding reversed both adiponectin and leptin gene expression. Peripheral injection of the beta(3)-adrenergic agonist, CL316,243, suppressed both leptin and adiponectin expression in WAT. A small but significant reduction in adiponectin expression in BAT was also observed following this treatment. Although CL316,23 lowered serum leptin levels markedly, it did not affect serum adiponectin levels. A chronic 7-day infustion of CL316,243 resulted in an elevation of adiponectin expression in WAT and serum concentrations in contrast to suppressions in both mRNA and serum levels of leptin by a similar treatment as previously reported. Chronic administration of leptin did not alter adiponectin synthesis in WAT compared to controls, but prevented the reduction in adiponectin synthesis associated with pair feeding. Food restriction through pair feeding also diminished adiponectin expression in BAT. Collectively, although leptin and adiponectin are inversely correlated with obesity, leptin does not appear to participate directly in adiponectin synthesis. The short-term regulation of the two adipokine expression in WAT is somewhat similar, perhaps subjective to common control of energy balance. The long-term regulation of adiponectin expression in WAT appears to be the opposite of that of leptin and may be more sensitive to changes in adiposity or insulin sensitivity.

Topics: Adiponectin; Adipose Tissue; Adipose Tissue, Brown; Adrenergic beta-3 Receptor Agonists; Adrenergic beta-Agonists; Animals; Brain; Dioxoles; Fasting; Gene Expression Regulation; Intercellular Signaling Peptides and Proteins; Leptin; Male; Obesity; Proteins; Rats; Rats, Inbred F344; RNA, Messenger; Tretinoin

Leptin is a peptide hormone that appears critical in regulating Fat metabolism. Recently, circulating leptin levels were reported higher in patients with alcoholic cirrhosis. In health, hepatic stellate cells store retinoids, but following liver injury they transdifferentiate into myofibroblast-like cells with loss of the retinoid stores. Leptin expression was demonstrated by detection of leptin mRNA by RT-PCR analysis and by immunohistochemistry viewed with confocal microscopy in transdifferentiated stellate cells after 14 days, or more, of culture. Leptin expression was not found in freshly isolated quiescent stellate cells. Leptin expression was not demonstrated in freshly isolated or cultured Kupffer cells. Treatment of activated stellate cells with either 1 microM retionic acid or 10 microM retinol acetate resulted in the inhibition of leptin mRNA expression. The observation that activated stellate cells in culture can express leptin has implications for understanding adipocyte biology in liver disease and treatment of malnutrition in cirrhotics.

Topics: Animals; Cell Differentiation; Cell Separation; Cells, Cultured; Diterpenes; Leptin; Liver; Male; Obesity; Protein Biosynthesis; Proteins; Rats; Rats, Sprague-Dawley; Retinyl Esters; RNA, Messenger; Tretinoin; Vitamin A

Topics: Adult; Aged; Amsacrine; Antibiotics, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Body Mass Index; Cytarabine; Daunorubicin; Female; Heart; Heart Failure; Humans; Leukemia, Promyelocytic, Acute; Male; Mercaptopurine; Obesity; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Remission Induction; Tretinoin