tretinoin and Metabolic-Syndrome

Elevated concentration of plasma non-esterified fatty acids (NEFA) is now recognized as a key factor in the onset of insulin-resistance and type 2 diabetes mellitus. During fasting, circulating NEFAs arise from white adipose tissue (WAT) as a consequence of lipolysis from stored triacylglycerols. However, a significant part of these FAs (30-70%) is re-esterified within the adipocyte, so that a recycling occurs and net FA output is much less than << true >> lipolysis. Indeed, a balance between two antagonistic processes, lipolysis and FA re-esterification, controls the rate of net FA release from WAT. During fasting, re-esterification requires glyceroneogenesis defined as the de novo synthesis of glycerol-3-P from pyruvate, lactate or certain amino acids. The key enzyme in this process is the cytosolic isoform of phosphoenolpyruvate carboxykinase (PEPCK-C; EC 4.1.1.32). Recent advance has stressed the role of glyceroneogenesis and of PEPCK-C in FA release from WAT. Results indicate that glyceroneogenesis is indeed important to lipid homeostasis and that a disregulation in this pathway may have profound pathophysiological effects. The present review focuses on the regulation of glyceroneogenesis and of PEPCK-C gene expression and activity by FAs, retinoic acids, glucocorticoids and the hypolipidemic class of drugs, thiazolidinediones.

Topics: Adipocytes; Adrenal Cortex Hormones; Animals; Esterification; Fatty Acids, Nonesterified; Gene Expression Regulation, Enzymologic; Glycerol; Glycerophosphates; Humans; Hypolipidemic Agents; Metabolic Syndrome; Mice; Phosphoenolpyruvate Carboxykinase (GTP); Thiazoles; Thiazolidinediones; Tretinoin; Triglycerides

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

In this prospective study, we evaluated the association of retinoic acid (RA) with the metabolic syndrome (MetS) in the Chinese population.. A total of 1042 nondiabetic adults from the population-based Nutrition and Health of Aging Population were prospectively followed up for 4 years. Serum RA concentrations was determined and its relationship with the MetS and its component was investigated.. At baseline, higher RA levels were inversely associated with the presence of MetS (odds ratio 0.61; 95% confidence interval [CI] 0.44–0.74, P < .001) after adjustment for age, gender, body mass index, the homeostasis model assessment index for insulin resistance (HOMA-IR), and other confounding factors. Subjects with lower RA levels had a progressively worse cardiometabolic risk profile at baseline. Serum RA levels were inversely associated with 8-iso-prostaglandin F2α (P < .001), high-sensitivity C-reactive protein (P = .015), and IL-6 (P = .020) and positively correlated with high-density lipoprotein cholesterol (P = .038). Among 825 subjects without MetS at baseline, 146 had developed it at 4 years. Serum RA by quartiles was inversely correlated with the incident MetS (adjusted hazard ratio 0.67; 95% CI 0.48–0.81, P = .006). Apart from HOMA-IR (P < .001), the baseline RA level was the only independent predictor of the development of the MetS during the 4-year follow-up (odds ratio 0.53; 95% CI 0.40–0.69; P < .001) after adjustment for age, gender, body mass index, and HOMA-IR.. The serum RA level is inversely associated with the development of MetS independently of adiposity and insulin resistance.

Topics: Adiposity; Age Factors; Aged; Body Mass Index; C-Reactive Protein; Cholesterol, HDL; Dinoprost; Female; Follow-Up Studies; Health Surveys; Humans; Insulin Resistance; Male; Metabolic Syndrome; Middle Aged; Prospective Studies; Sex Factors; Tretinoin

Topics: Adipogenesis; Adipose Tissue; Animals; Cells, Cultured; Metabolic Syndrome; Mice; Mice, Obese; PPAR gamma; Retinaldehyde; Signal Transduction; Tretinoin; Vitamin A