epidermal-growth-factor and Obesity

Previously, we showed that knockout mice homozygous for deficiency of the mercapturic acid pathway (MAP) transporter protein, RLIP (RLIP

Topics: Acetylcysteine; Adipokines; Animals; Carcinogenesis; Carcinogens; Carrier Proteins; Clathrin; Cytokines; Epidermal Growth Factor; GTPase-Activating Proteins; Humans; Infant; Insulins; Male; Mice; Neoplasms; Obesity; Oxidative Stress; Peptide Hormones; Transforming Growth Factor beta; Tumor Suppressor Protein p53

We report the case of a 63-year-old obese man with a rapid-onset of widespread acanthosis nigricans (AN) in the setting of having recently initiated treatment with niacin for dyslipidemia. Although obesity and insulin-resistance are risk factors for AN, AN associated with endocrine dysfunction tends to have a more gradual onset and limited involvement. Owing to our patient's age, the rapid onset, and extensive distribution of his eruption, we initially were concerned about paraneoplastic AN. However, an evaluation for a malignant condition was negative. The timing of the onset of our patient's eruption within several months of starting niacin therapy is consistent with niacin-induced AN. Niacin is known to cause rapidly progressive, widespread AN that is reversible upon discontinuation of the medication. We discuss the pathogenesis of AN, which is thought to be the final common manifestation of stimulation of different subtypes of tyrosine kinase receptors by various epidermal growth factors.

Topics: Acanthosis Nigricans; Cardiovascular Diseases; Diagnosis, Differential; Dyslipidemias; Epidermal Growth Factor; Humans; Hyperinsulinism; Hypolipidemic Agents; Insulin Resistance; Male; Middle Aged; Niacin; Obesity; Paraneoplastic Syndromes; Receptor Protein-Tyrosine Kinases

Prostate cancer, the third most common cancer in men worldwide, varies substantially according to geographic region and race/ethnicity. Obesity and associated endocrine variation are foremost among the risk factors that may underlie these regional and ethnic differences. The association between obesity and prostate cancer incidence is complex and has yielded inconsistent results. Studies that have linked obesity with prostate cancer mortality, advanced stage disease, and higher grade Gleason score, however, have produced more consistent findings, indicating that obesity may not necessarily increase the risk of prostate cancer, but may promote it once established. Additionally, metabolic syndrome, which includes disturbed glucose metabolism and insulin bioactivity, may also be associated with prostate carcinogenesis. Adipokines, defined as biologically active polypeptides produced by adipose tissue, have been linked with a number of carcinogenic mechanisms, including angiogenesis, cell proliferation, metastasis, and alterations in sex-steroid hormone levels. A number of emerging studies have implicated the role of adipokines in prostate carcinogenesis. This review explores the specific roles of several adipokines as putative mediating factors between obesity and prostate cancer with particular attention to leptin, interleukin-6 (IL-6), heparin-binding epidermal growth factor-like growth factor (HB-EGF), vascular endothelial growth factor (VEGF) and adiponectin.

Topics: Adipose Tissue; Epidermal Growth Factor; Heparin-binding EGF-like Growth Factor; Humans; Intercellular Signaling Peptides and Proteins; Interleukin-6; Leptin; Male; Obesity; Prostatic Neoplasms; Risk Factors; Vascular Endothelial Growth Factor A

Topics: Adiponectin; Animals; Epidermal Growth Factor; Estrogens; Female; Humans; Insulin Resistance; Lipoprotein Lipase; Menopause; Metabolic Syndrome; Obesity; Tumor Necrosis Factor-alpha

Topics: Biomarkers; Coronary Disease; Cystitis, Interstitial; Enzyme-Linked Immunosorbent Assay; Epidermal Growth Factor; Female; Gastrointestinal Tract; Heparin-binding EGF-like Growth Factor; Hepatectomy; Humans; Intercellular Signaling Peptides and Proteins; Liver Regeneration; Obesity; Pregnancy

To elucidate the biological characteristics of adipose tissue, we analyzed the gene expression profile of visceral and subcutaneous fat. Unexpectedly, adipose tissue, especially visceral fat, expressed a variety of genes for secretory proteins. About 30% of the genes expressed in visceral adipose tissue encoded secretory proteins and most were biologically active molecules, which we called adipocytokines. We found plasminogen activator inhibitor type 1 and heparin binding EGF-like growth factor. Production of these atherogenic adipocytokines was shown to increase with the accumulation of visceral fat, which may be one of the mechanisms of vascular disease in visceral obesity. We found a unique and novel collagen-like protein, adiponectin, encoded by the most abundantly expressed gene in adipose tissue, termed APM1 (adipose most abundant gene transcript-1). Plasma levels of adiponectin ranged from 0.3 to approximately 3 mg/dl but were decreased in patients with visceral obesity, type 2 diabetes and coronary artery disease (CAD). Screening for mutations in the adiponectin gene revealed that patients carrying a missense mutation showed markedly decreased plasma levels of adiponectin and had CAD. These data suggest that hypoadiponectinemia may be considered an important risk factor for CAD. Cell biology studies revealed that adiponectin has a potent inhibitory effect on the expression of adhesion molecules in endothelial cells and an inhibitory effect on the expression in macrophages. In order to confirm these antidiabetic and antiatherogenic functions of adiponectin, we developed adiponectin knockout mice. Adiponectin knockout mice showed severe insulin resistance and impaired glucose metabolism when fed a high-fat, high-sucrose diet. Knockout mice also developed intimal thickening in response to endothelial injury.

Topics: Adiponectin; Adipose Tissue; Animals; Arteriosclerosis; Coronary Artery Disease; Epidermal Growth Factor; Heparin-binding EGF-like Growth Factor; Humans; Intercellular Signaling Peptides and Proteins; Obesity; Plasminogen Activator Inhibitor 1; Proteins; Risk Factors

Early graft failure (EGF) is a devastating postoperative complication following heart transplant. Institutional studies have modelled donor and recipient risk factors predictive of graft failure. To date, no studies have assessed specific recipient profiles associated with mortality after recipients suffer from EGF. The objective of this study was to identify this recipient profile.. We performed a retrospective review of patients in the United Network for Organ Sharing database undergoing heart transplant from August 2000 to September 2019. EGF was defined as graft dysfunction at 24 hours post-heart transplant. The primary outcome was 90-day mortality. To isolate recipient characteristics associated with mortality, we performed the univariate analysis on 24 recipient characteristics adjusted for high-risk donor characteristics (ischaemic time, donor age, race mismatch, BUN/creatinine ratio) predictive of 1-year mortality (P < 0.2). We then performed backward stepwise multivariable regression adjusted for identified donor characteristics to determine recipient characteristics associated with mortality after EGF (P < 0.05).. We identified 302 patients diagnosed with post-transplant EGF. Among these patients, mortality was 82% within 90 days of transplantation. Adjusted univariate analysis identified 7 factors associated with mortality. Adjusted backward stepwise multivariable regression identified BMI > 30 as predictive of mortality at 90 days after EGF.. Patients who develop EGF after heart transplant are at high risk for mortality. Careful discussion regarding transplant candidacy and risk is warranted in obese patients. In addition, minimizing donor factors associated with graft dysfunction is critical during preoperative planning in these recipients.

Topics: Epidermal Growth Factor; Graft Survival; Heart Transplantation; Humans; Obesity; Retrospective Studies; Risk Factors; Tissue Donors; Treatment Outcome

Obesity is a serious problem among Saudis because of the country's affluent lifestyle. Obesity is associated with various metabolic disorders and characterized by low-grade inflammation that leads to the release of pro-inflammatory cytokines, human growth factors (GFs), lipids, aberrant adipokines, and other chemokines from adipose tissue. The objective of this study is to delineate the effects of GFs on microbiota and their relationship to body mass index (BMI) and food habits.. In a cross-sectional study, 32 randomly selected participants (16 males and 16 females) were enrolled in a survey covering their sociodemographic information, medical history, lifestyle, and dietary practices. The information on diet, health condition, food and drink intake habits were examined under four distinct BMI categories: normal, underweight, overweight, and obese. The participants' serum samples were analyzed for the various GFs using a human magnetic 30-plex panel multiplex assay. Bioinformatics analysis was performed to investigate which bacterial taxa are enriched and to predict the functional profiles of the samples.. Correlational studies revealed sex-based differences between GFs and microbiota. Females exhibited a significant correlation between epidermal GF (EGF) and Proteobacteria, whereas males showed a significant correlation between fibroblast GF-basic and Actinobacteria. Interestingly, a combined analysis of both sexes showed a significant correlation between EGF and vascular endothelial GF with Firmicutes. The data in the underweight group revealed a correlation between granulocyte colony-stimulating factor (G-CSF) and hepatocyte GF with Firmicutes. In the obese group, a correlation was found between G-CSF and Actinobacteria.. Our results identified links between GFs, microbiota, and BMI in a Saudi cohort. The insights from this preliminary study will contribute to the predictive diagnosis of obesity. However, further research involving a larger cohort will be necessary to understand the mechanistic aspects of these GFs to provide biomarkers of potential obesity.

Topics: Body Mass Index; Cross-Sectional Studies; Epidermal Growth Factor; Feeding Behavior; Female; Humans; Male; Microbiota; Obesity; Overweight; Thinness

Adipose tissue is hypothesized to play a vital role in regulation of feed efficiency (FE; efficiency in converting energy and nutrients into tissue), of which improvement will simultaneously reduce environmental impact and feed cost per pig. The objective of the present study was to sequence the subcutaneous adipose tissue transcriptome in FE-divergent pigs (n = 16) and identify relevant biological processes underpinning observed differences in FE. We previously demonstrated that high-FE pigs were associated with lower fatness when compared to their counterparts. Here, ontology analysis of a total of 209 annotated genes that were differentially expressed at a p < 0.01 revealed establishment of a dense extracellular matrix and inhibition of capillary formation as one underlying mechanism to achieve suppressed adipogenesis. Moreover, mechanisms ensuring an efficient utilization of lipids in high-FE pigs might be orchestrated by upstream regulators including CEBPA and EGF. Consequently, high-FE adipose tissue could exhibit more efficient cholesterol disposal, whilst inhibition of inflammatory and immune response in high-FE pigs may be an indicator of an optimally functioning adipose tissue. Taken together, adipose tissue growth, extracellular matrix formation, lipid metabolism and inflammatory and immune response are key biological events underpinning the differences in FE. Further investigations focusing on elucidating these processes would assist the animal production industry in optimizing strategies related to nutrient utilization and product quality.

Topics: Adipose Tissue; Adiposity; Animal Feed; Animals; CCAAT-Enhancer-Binding Proteins; Epidermal Growth Factor; Extracellular Matrix; Gene Expression Profiling; Gene Expression Regulation; Gene Regulatory Networks; Immunity, Cellular; Lipid Metabolism; Obesity; Swine; Transcriptome

Adipose tissue produces different inflammatory cytokines which compromise bone mineral accrual during puberty. Vascular endothelial growth factor (VEGF), epidermal growth factor (EGF), interleukin (IL)-8, and interferon-gamma (IFN-γ) are significantly related to bone mineral accrual during pubertal maturation in boys with different BMI values.. This longitudinal study aims to identify the inflammatory markers that most strongly associate with pubertal bone mineral density (BMD) increment in boys with overweight and obesity (OWB).. Twenty-six OWB and 29 normal-weight boys were followed yearly for 3 years to measure changes in 12 serum inflammatory markers, BMD (by DXA), and apparent volumetric BMD. The OWB group was further divided into two subgroups according to their BMI gain during the 3-year period. Data through time points presented as slopes were used to calculate correlation coefficients to explore the possible relationships between variables of interest. In the whole study group, linear mixed effects (LME) models were also used.. Increment in serum VEGF concentration was inversely associated with an increase in total body (TB) BMD (r = - 0.82, P = 0.02) and TB bone mineral content (BMC)/height (r = - 0.82, P = 0.02) in those OWB whose BMI gain was higher during pubertal years. In the whole study group, the LME model confirmed the inverse association between VEGF and TB BMC/height (P < 0.05). EGF was inversely associated with LS BMD and LS BMAD (P < 0.05), whereas there was a positive association between IL-8 and TB BMAD and between IFN-γ and LS BMD (P < 0.05).. Lower increment in BMD in OWB with higher BMI gain is associated with increasing serum VEGF concentration during pubertal maturation. VEGF, EGF, IL-8, and IFN-γ are significantly associated with BMD during pubertal maturation in boys with different BMI values.

Topics: Anthropometry; Biomarkers; Body Mass Index; Child; Cytokines; Epidermal Growth Factor; Humans; Inflammation Mediators; Longitudinal Studies; Male; Obesity; Overweight; Puberty; Sexual Maturation; Testosterone; Vascular Endothelial Growth Factor A

Circulating oxidative stress and pro-inflammatory markers change after regular physical exercise; however, how a short session of acute physical activity affects the inflammatory status and redox balance in sedentary individuals is still unclear. Aim of this study is to assess antioxidant and inflammatory parameters, both at rest and after acute exercise, in sedentary young men with or without obesity. Thirty sedentary male volunteers, aged 20-45 (mean age 32 ± 7 years), were recruited, divided into 3 groups (normal weight: BMI < 25 kg/m2; overweight to moderate obesity: 25-35 kg/m2; severe obesity: 35-40 kg/m2), and their blood samples collected before and after a 20-min run at ~ 70% of their VO2max for the measurement of Glutathione Reductase, Glutathione Peroxidase, Superoxide Dismutase, Total Antioxidant Status (TAS) and cytokines (IL-2, IL-4, IL-6, IL-8, IL-10, IL-1α, IL-1β, TNFα, MCP-1, VEGF, IFNγ, EGF). Inter-group comparisons demonstrated significantly higher Glutathione Reductase activity in severely obese subjects in the post-exercise period (P = 0.036), and higher EGF levels in normal weight individuals, either before (P = 0.003) and after exercise (P = 0.05). Intra-group comparisons showed that the acute exercise stress induced a significant increase in Glutathione Reductase activity in severely obese subjects only (P = 0.007), a significant decrease in MCP-1 in the normal weight group (P = 0.02), and a decrease in EGF levels in all groups (normal weight: P = 0.025, overweight/moderate obesity: P = 0.04, severe obesity: P = 0.018). Altogether, these findings suggest that in sedentary individuals with different ranges of BMI, Glutathione Reductase and distinct cytokines are differentially involved into the adaptive metabolic changes and redox responses induced by physical exercise. Therefore, these biomarkers may have the potential to identify individuals at higher risk for developing diseases pathophysiologically linked to oxidative stress.

Topics: Adult; Biomarkers; Body Mass Index; Chemokine CCL2; Epidermal Growth Factor; Exercise; Fasting; Glutathione Peroxidase; Glutathione Reductase; Humans; Interferon-gamma; Interleukins; Male; Middle Aged; Obesity; Oxidative Stress; Sedentary Behavior; Severity of Illness Index; Superoxide Dismutase; Tumor Necrosis Factor-alpha; Vascular Endothelial Growth Factor A

There is a growing interest in low-grade inflammatory and metabolic alterations in patients with chronic schizophrenia (SCH).. Inflammatory (tumor-necrosis factor-α [TNF-α], interferon-γ [IFN-γ], interleukins [IL-1α, IL-1β, IL-2, IL-4, IL-6, IL-8, IL-10], monocyte chemo-attractant protein-1 [MCP-1]) and growth factors (vascular endothelial growth factor [VEGF], epidermal growth factor [EGF]) were measured in blood serum samples of 105 SCH patients and 148 control subjects (CS). Simultaneously the clinical biomarkers (C-reactive protein [CRP], triglycerides [TG], low-density lipoprotein [LDL-c] and high-density lipoprotein [HDL-c] cholesterol, glycated hemoglobin [HbA1c]) were measured, and body mass index (BMI) was calculated for patients.. Several cyto-/chemokines (IFN-γ, MCP-1, IL-2, IL-6, IL-8 and IL-10) were significantly (P<0.0000001) elevated in SCH patients compared to CS. Odds ratios, obtained from logistic regression analyses, were significantly elevated for IL-2, IL-6, IL-10, INF-γ, and decreased for TNF-α in SCH group. Among the patients, higher IL-2, IL-6, INF-γ and lower MCP-1 levels as well as male gender were together significant (P<0.000001) predictors of higher HbA1c levels, and TG/HDL-c parameter was associated with ratios of INF-γ/IL-10 (P=0.004), and INF-γ/IL-4 (P=0.049), HbA1c (P=0.005), INF-γ (P=0.009), as well as LDL-c (P=0.02) levels.. IL-2, IL-6, IL-10 and IFN-γ were the most significant SCH-related markers among the measured cytokines in our patient group. Furthermore, significant associations between pro-/anti-inflammatory imbalance and HbA1c as well as cardio-metabolic risk marker (TG/HDL-c) were observed, indicating higher risks of diabetes and cardiovascular diseases among SCH patients.

Topics: Adult; Cytokines; Diabetes Mellitus, Type 2; Epidermal Growth Factor; Female; Humans; Inflammation; Male; Middle Aged; Obesity; Schizophrenia; Vascular Endothelial Growth Factor A

Obese infants are more susceptible to develop adulthood obesity and its related comorbidities. Previous studies have shown the presence of hormones and growth factors in maternal breast milk that may influence infant adiposity. The aim of this study was to investigate differences in concentrations of three hormones and two growth factors in the breast milk of mothers with obese and non-obese infants.. In this cross-sectional study, 40 mothers with overweight or obese infants (weight for length percentile >97) and 40 age-matched mothers with normal-weight infant (-10 < weight for length percentile < 85) who were between 2 and 5 months of age were enrolled. Anthropometric indices of infants and mothers were measured by routine methods. Breast milk concentrations of ghrelin and adiponectin, leptin, epithelial growth factor (EGF) and insulin-like growth factor-1 (IGF-1) were measured using enzyme-linked immunosorbent assay methods.. The mean breast milk concentration of ghrelin was higher in mothers with normal-weight infants, 137.50 pg/ml, than in mothers with obese infants, 132.00 pg/ml (P=0.001). This was also true regarding the concentration of EGF in mothers with (0/04 ng/ml) and without (0/038 ng/ml) normal-weight infants (P=0.01). No significant differences were observed in concentrations of leptin, adiponectin and IGF-1 between two groups (P > 0.05). There was also a significant positive correlation between EGF and ghrelin in both groups.. This study revealed that there was a correlation between ghrelin and EGF level in breast milk of mothers with obese and non-obese infants, suggesting a possible regulatory effect of these two hormones on weight in infants.

Topics: Adiponectin; Adult; Body Weight; Breast Feeding; Case-Control Studies; Child Development; Cross-Sectional Studies; Epidermal Growth Factor; Female; Ghrelin; Humans; Infant; Infant Nutritional Physiological Phenomena; Insulin-Like Growth Factor I; Leptin; Milk, Human; Mothers; Obesity; Overweight; Pregnancy; Young Adult

Obesity is accompanied by an increase in the size and the number of adipocytes. As adipocytes are thought to differentiate from pre-adipocytes, we postulate that non-adipogenic fibroblasts contribute to adipocyte formation under certain conditions such as obesity. We report for the first time that NIH-3T3 fibroblasts, which are generally considered to be non-adipogenic, can be converted into mature adipocytes by treatment with a defined hormone mixture comprising EGF (epidermal growth factor), HGF (hepatocyte growth factor), Dex (dexamethasone) and insulin. Furthermore, NIH-3T3 cells transplanted into obese immunodeficient NOD/SCID (non-obese diabetic/severe combined immunodeficient) mice formed adipocytes in vivo. Interestingly, the mixture elicited conversion of NIH-3T3 cells directly into adipocytes without a preceding pre-adipocyte stage. Functional analysis revealed that each component of the mixture was necessary for the induction of adipogenesis, including Dex which inhibited the cell proliferation stimulated by EGF. Upon profiling the signalling pathways employed by EGF and HGF, we found STAT5 (signal transducer and activator of transcription 5) signalling to be activated, predominantly at the levels of both transcription and post-translational modification. Inhibition of the STAT5 pathway, either by genetic knockdown or a specific pharmacological agent, blocked adipogenesis in NIH-3T3 cells. Taken together, these data not only establish a newly recognized grouping of factors that can induce trans-differentiation of non-adipogenic fibroblasts into adipocytes, but also give us a greater understanding of obesity.

Topics: 3T3-L1 Cells; Adipocytes; Adipogenesis; Animals; Cell Transdifferentiation; Dexamethasone; Epidermal Growth Factor; Fibroblasts; Gene Knockdown Techniques; Hepatocyte Growth Factor; Insulin; Mice; Mice, Inbred NOD; Mice, SCID; NIH 3T3 Cells; Obesity; Signal Transduction; STAT5 Transcription Factor

obesity, characterized by adiposity excess, is associated with endothelial dysfunction and possible inflammatory state with release of cytokines that determine endothelial function and can trigger chronic diseases. The dietary pattern are associated with the synthesis these cytokines. Fruits as the acai, which is rich in flavonoids, have a direct and beneficial effect on the control of this inflammatory process through the exercised antioxidant capacity.. to evaluate the effect of acai pulp consumption on the inflammatory markers, anthropometric measurements, body composition, biochemical and dietary parameters in healthy women.. forty women, were divided in 25 eutrophic and 15 with overweight. They intaked 200 g of acai pulp during 4 weeks. Anthropometric measurements, body composition, inflammatory markers, biochemical data, dietary intake and dietary antioxidants capacity were evaluated before and after the intervention.. after the intervention, there was significant increase of EGF (p = 0.021) and PAI- 1(p = 0.011) in overweight women. Moreover, there was increase in body weight (p = 0.031), body mass index (p = 0.028), percentage of truncal fat (p = 0.003) and triceps skinfold thickness (p = 0.046) in eutrophic women. However, the skinfold thickness (p = 0.018) and total body fat (p = 0.016) decreased in overweight women. There was reduction of total protein (p = 0.049) due to the globulin reduction (p = 0.005), but the nutritional status was maintained in eutrophic group.. the intake of 200g acai pulp, modulated the EGF and PAI-1 expression, possibly by modulation of acai on the parameters of body composition, dietary, clinical, biochemical and inflammatory, led to a redistribution and resizing of body fat of the trunk area, and presumably increased visceral fat.. Introducción: la obesidad, que se caracteriza por el exceso de adiposidad, se asocia con disfunción endotelial y posible estado inflamatorio con liberación de citoquinas que determinan la función endotelial y pueden desencadenar enfermedades crónicas. El patrón de dieta está asociado con la síntesis de estas citoquinas. Los frutos de el acai, que es rico en flavonoides, tienen un efecto directo y positivo en el control de este proceso inflamatorio a través de los ejercicios de la capacidad antioxidante. Objetivo: evaluar el efecto del consumo de pulpa de acai en los marcadores inflamatorios, las medidas antropométricas, la composición corporal y los parámetros bioquímicos y dietéticos en mujeres sanas. Métodos: cuarenta mujeres fueron divididas en 25 eutróficas y 15 con sobrepeso. Se las adeministró 200 g de pulpa de acai durante 4 semanas. Antes y después de la intervención se evaluaron: medidas antropométricas, composición corporal, marcadores inflamatorios, datos bioquímicos, ingesta dietética y antioxidantes en la dieta. Resultados y discusión: después de la intervención, hubo un aumento significativo de EGF (p = 0,021) y PAI-1 (p = 0,011) en las mujeres con sobrepeso. Por otra parte, en las mujeres eutróficas hubo aumento del peso corporal (p = 0,031), el índice de masa corporal (p = 0,028), el porcentaje de grasa del tronco (p = 0,003) y el espesor del pliegue cutáneo del tríceps (p = 0,046). Sin embargo, el espesor del pliegue cutáneo (p = 0,018) y la grasa corporal total (p = 0,016) se redujeron en las mujeres con sobrepeso. Hubo una reducción de la proteína total (p = 0,049) debida a la disminución de globulina (p = 0,005), pero el estado nutricional se mantuvo en el grupo eutrófico. Conclusión: la ingesta de 200 g de pulpa de acai modula el EGF y PAI-1 de expresión, posiblemente por la modulación del acai en los parámetros de la composición corporal, la dieta, clínicos, bioquímicos e inflamatorios, lo que dio lugar a una redistribución y modificación del tamaño de la grasa corporal de la zona del tronco, y, presumiblemente, un aumento de la grasa visceral.

Topics: Adolescent; Adult; Anthropometry; Biomarkers; Body Composition; Diet; Epidermal Growth Factor; Euterpe; Feeding Behavior; Female; Fruit; Healthy Volunteers; Humans; Inflammation Mediators; Obesity; Overweight; Plasminogen Activator Inhibitor 1; Young Adult

Calorie restriction is a common strategy for weight loss in obese individuals. However, little is known about the impact of moderate hypocaloric diets on obesity-related laboratory parameters in a short-term period. Aim of this study was to evaluate the variation of laboratory biomarkers in obese individuals following a Mediterranean, hypocaloric (1400-1600 Kcal/die) diet. 23 obese, pharmacologically untreated patients were enrolled and subjected to the determination of anthropometric variables and blood collection at baseline, 1 and 4 months after diet initiation. After 4 months of calorie restriction, we observed a significant decrease in body weight and BMI (both P < 0.0001), insulin (P = 0.037), HOMA-IR (P = 0.026), leptin (P = 0.008), and LDH (P = 0.023) and an increase in EGF (P = 0.013). All these parameters, except LDH, varied significantly already at 1 month after diet initiation. Also, lower levels of insulin (P = 0.025), leptin (P = 0.023), and EGF (P = 0.035) were associated with a greater (>5%) weight loss. Collectively, our data support a precocious improvement of insulin and leptin sensitivity after a modest calorie restriction and weight reduction. Moreover, EGF and LDH may represent novel markers of obesity, which deserve further investigations.

Topics: Adipokines; Anthropometry; Biomarkers; Body Mass Index; Caloric Restriction; Diet; Diet, Mediterranean; Epidermal Growth Factor; Female; Humans; Insulin; Insulin Resistance; L-Lactate Dehydrogenase; Leptin; Male; Middle Aged; Obesity; Prospective Studies; Weight Loss

In adults, circulating inflammatory mediators and activated CD14(++) monocytes link obesity to its metabolic and cardiovascular complications. However, it is largely unknown whether these inflammatory changes already occur in childhood obesity. To survey inflammatory changes during the early stages of obesity, we performed a comprehensive analysis of circulating inflammatory mediators, monocyte populations and their function in childhood obesity.. In lean and obese children aged 6 to 16 years (n = 96), 35 circulating inflammatory mediators including adipokines were measured. Hierarchical cluster analysis of the inflammatory mediator profiles was performed to investigate associations between inflammatory mediator clusters and clinical variables. Whole-blood monocyte phenotyping and functional testing with the toll-like receptor 4 ligand, lipopolysaccharide, were also executed.. First, next to leptin, the circulating mediators chemerin, tissue inhibitor of metalloproteinase 1, EGF and TNF receptor 2 were identified as novel inflammatory mediators that are increased in childhood obesity. Second, cluster analysis of the circulating mediators distinguished two obesity clusters, two leanness clusters and one mixed cluster. All clusters showed distinct inflammatory mediator profiles, together with differences in insulin sensitivity and other clinical variables. Third, childhood obesity was associated with increased CD14(++) monocyte numbers and an activated phenotype of the CD14(++) monocyte subsets.. Inflammatory mediator clusters were associated with insulin resistance in obese and lean children. The activation of CD14(++) monocyte subsets, which is associated with increased development of atherosclerosis in obese adults, was also readily detected in obese children. Our results indicate that inflammatory mechanisms linking obesity to its metabolic and cardiovascular complications are already activated in childhood obesity.

Topics: Adolescent; Case-Control Studies; Cell Count; Chemokines; Child; Cluster Analysis; Comorbidity; Epidermal Growth Factor; Female; Humans; Inflammation; Inflammation Mediators; Intercellular Signaling Peptides and Proteins; Leptin; Lipopolysaccharide Receptors; Male; Monocytes; Obesity; Receptors, Tumor Necrosis Factor, Type II; Regression Analysis; Tissue Inhibitor of Metalloproteinase-1; Vascular Endothelial Growth Factor A

A set of common epidemiologic risk factors have been associated with the risk of breast cancer despite of its molecular sub-classifications. We implemented a case series study with the primary objective of evaluating if obesity is associated with the diagnostic risk of "ER+ and/or PR+, HER2+", "ER-/PR-, HER2-", or "ER-/PR-, HER2+" relative to the most commonly diagnosed subtype of breast carcinoma, "ER+ and/or PR+, HER2-".. Demographic, clinical and pathologic data were collected from existing databases. The statuses of HER2/neu biomarker and hormone receptors were dichotomized as either positive or negative. Immunohistochemical staining was used to assess the prevalence of different subtypes. Body mass index was calculated from weight and height data collected at the time of consultation.. Findings from the present study suggest that excess body weight decreases the diagnostic risk of "ER-/PR-, HER2-", or "ER-/PR-, HER2-" relative to "ER+ and/or PR+, HER2-". Obese and overweight women are more likely to be diagnosed with to "ER+ and/or PR+, HER2-", the subtype that has best prognosis and mostly associated with personal lifestyle. Weight gain with the population attributable-risk factor of 21.3% contributes the most to the incidence of invasive post menopausal breast cancer. Younger pre-menopausal women were more likely to be diagnosed with "ER+ and/or PR+, HER2+". In younger women biology of breast cancers with positive expression for hormone receptors and epidermal growth factor is a complex that extends beyond the currently assessed prognostic markers.

Topics: Biomarkers, Tumor; Body Mass Index; Breast Neoplasms; Epidermal Growth Factor; Female; Humans; Logistic Models; Middle Aged; Obesity; Receptor, ErbB-2; Receptors, Estrogen; Receptors, Progesterone; Risk Factors; United States

Recent evidence has shown that activation of phosphatidyinositol-3-kinase (PI3K) and Akt, necessary for insulin stimulation of glucose transport, is impaired in insulin resistance. It is unknown, however, which Akt isoform shows impaired activation in insulin resistance. Additionally, related growth factors (epidermal or platelet-derived vascular) also stimulate PI3K, but it is unknown whether production of 3,4,5 phosphatidyinositol is sufficient to stimulate glucose transport in insulin-resistant muscle. Moreover, these studies were performed in rodents, and little data exists from humans. Hence, we investigated the stimulation of PI3K and Akt-1, -2, and -3 by insulin and epidermal growth factors (EGFs) in skeletal muscles from lean and obese insulin-resistant humans. Insulin activated all Akt isoforms in lean muscles, whereas only Akt-1 was activated in obese muscles. Insulin receptor substrate (IRS)-1 was associated with PI3K activity, which is necessary for Akt activation by insulin, and was reduced in obese muscles, and this was accompanied by decreased IRS-1 expression. In contrast, insulin- or EGF-stimulated phosphotyrosine-associated PI3K activity was not different between lean and obese muscles. These results show that a defect in the ability of insulin to activate Akt-2 and -3 may explain the impaired insulin-stimulated glucose transport in insulin resistance. Additionally, these data also show that different upstream or downstream signals may regulate the activity of the various Akt isoforms.

Topics: Adult; Body Mass Index; Deoxyglucose; Enzyme Activation; Epidermal Growth Factor; Female; Glycogen Synthase Kinase 3; Glycogen Synthase Kinase 3 beta; Humans; Insulin; Insulin Receptor Substrate Proteins; Insulin Resistance; Male; Muscle, Skeletal; Obesity; Oncogene Proteins; Phosphatidylinositol 3-Kinases; Phosphoproteins; Phosphotyrosine; Protein Serine-Threonine Kinases; Proto-Oncogene Proteins; Proto-Oncogene Proteins c-akt; Signal Transduction

The mechanism by which the obese subjects are more associated with vascular disease remains unclear. We reported that the adipose tissues produce and secrete many bioactive molecules, conceptualized as adipocytokines. Heparin-binding epidermal growth factor (EGF)-like growth factor (HB-EGF), produced locally by vascular macrophages and smooth muscle cells, has been suggested to induce the migration and proliferation of vascular smooth muscle cells. The current study reveals that (1) HB-EGF mRNA is abundantly expressed in human adipose tissue, (2) HB-EGF mRNA increases in the fat tissues of obese mice, (3) plasma HB-EGF levels increase in parallel with fat accumulation in human, and (4) the subjects with coronary artery disease have higher plasma HB-EGF levels, associated with fat accumulation. These results suggest that increased plasma HB-EGF derived from the accumulated fat contributes to the higher incidence of vascular disease in obesity, proposing HB-EGF as an adipocytokine directly linking adipovascular axis.

Topics: Adipose Tissue; Adult; Aged; Animals; Coronary Artery Disease; Epidermal Growth Factor; Heparin-binding EGF-like Growth Factor; Humans; Intercellular Signaling Peptides and Proteins; Male; Mice; Mice, Obese; Middle Aged; Obesity; RNA; Statistics as Topic; Tissue Distribution

Ovariectomy (Ovx) of mice significantly increases the epidermal growth factor (EGF) concentration in the submandibular gland. To elucidate the role of this elevated EGF in obesity of Ovx mice, we examined the effects of sialoadenectomy (Sx) and anti-EGF rabbit antiserum administration on the body weight (BW) gain and carcass fat deposition in Ovx animals. Studies were performed in four groups of mice consisting of control, Ovx, Ovx+Sx, and Ovx+anti-EGF groups. Ovx increased the BW gain compared with the control animals, whereas Sx and anti-EGF significantly reduced it. Although the relative weights (weight ratio to BW) of the liver and kidney were not significantly changed by Ovx, Sx, or anti-EGF treatment of Ovx mice, the relative weights of mesenteric, parametrial, and subcutaneous fat tissues were increased in Ovx mice, and this increase was significantly reduced by Sx or anti-EGF administration. Ovx induced adipocyte hypertrophy, and this effect was eliminated by Sx and anti-EGF. Moreover, acyl-CoA synthetase mRNA level was increased by Ovx, and this increase was reduced by Sx and anti-EGF in mesenteric fat tissue. These findings suggest that elevation of EGF may play a role in the induction of obesity in Ovx mice.

Topics: Acetate-CoA Ligase; Adipose Tissue; Animals; Body Weight; Eating; Epidermal Growth Factor; Female; Kidney; Lipids; Liver; Mice; Mice, Inbred C3H; Obesity; Organ Size; Ovariectomy; RNA, Messenger; Submandibular Gland

Epidermal growth factor (EGF) is a potent inhibitor of adipose differentiation in vitro and delays adipose tissue development in vivo. Here we show that in the homozygous male obese mice the level of EGF in the submaxillary gland and plasma is significantly lower than in the glands and plasma of age-matched control littermates. This EGF deficiency in ob/ob mice was observed as early as 5 wk of age when obesity had just become apparent and was also found in adult mice. The level of prepro-EGF mRNA expression in the submaxillary gland was also lower in obese mice than in control littermates. However, the level of kidney prepro-EGF mRNA was the same in mice with both phenotypes, suggesting that the regulation of prepro-EGF mRNA expression is different in both tissues. These results indicate that genetic obesity in mice is accompanied by a decrease in the production of EGF.

Topics: Adipose Tissue; Animals; Body Weight; Epidermal Growth Factor; Female; Kidney; Male; Mice; Mice, Inbred C57BL; Mice, Obese; Obesity; Organ Size; Protein Precursors; RNA, Messenger; Submandibular Gland