title: Hormonal regulation of intracellular lipolysis in C57BL/6J mice: effect of diet-induced adiposity and data normalization.
abstract: The breakdown of intracellular triglycerides in adipose tissue provides fatty acids and glycerol as substrates for oxidation. However, the exposure of target organs to excess free fatty acids is associated with the development of insulin resistance and impaired regulation of carbohydrate metabolism, suggesting that the control of triglyceride breakdown is an important factor in balancing health and disease. We have studied the temporal influence of diet-induced changes in adiposity on the response of intracellular lipolysis to epinephrine +/- insulin using freshly isolated adipocytes from C57BL/6J mice fed a low-fat (10% kcal) or high-fat (HF, 45% kcal) diet for 1, 4, or 12 weeks. In this model, we also tested how data normalization affects the interpretation. The contribution of the epididymal fat to total body mass increased by approximately 15%, 45%, and 100% after 1, 4, and 12 weeks of HF diet consumption, respectively. In addition, HF feeding led to an increase in fasting insulin, that is, approximately 2-fold greater in HF- vs low-fat-fed mice at 4 and 12 weeks. We found that diet-induced changes in adiposity did not alter the lipolytic response to epinephrine when data were normalized per DNA (ie, per cell); however, the lipolytic potential of the organ (ie, the lipolytic rate per cell multiplied by the total number of cells) was increased in isolated adipocytes after 4 and 12 weeks of HF feeding. We also observed a marked impairment in insulin-mediated inhibition of epinephrine-stimulated lipolysis after 4 and 12 weeks of HF feeding, demonstrating that diet-induced adiposity leads to insulin resistance in adipocytes. In conclusion, HF feeding in mice leads to greater rates of lipolysis via (1) an increase in the number of fat cells and (2) a defect in insulin signaling in adipocytes. The combination of these 2 alterations on the control of intracellular lipolysis suggests a mechanism(s) that (partly) explains how target organs could be exposed to excess lipid-derived energy substrates, for example, free fatty acids and glycerol.
authors.affiliation: Department of Nutrition, Case Western Reserve University School of Medicine, Cleveland, OH 44106, USA.
authors.forename: Ilya R
authors.initials: IR
authors.lastname: Bederman
authors.forename: Stephen F
authors.initials: SF
authors.lastname: Previs
mesh_terms: D017667:Adipocytes / Q000187:drug effects / Q000378:metabolism*; D000273:Adipose Tissue / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D004040:Dietary Carbohydrates / Q000008:administration & dosage*; D004041:Dietary Fats / Q000378:metabolism; D004837:Epinephrine / Q000494:pharmacology*; D005230:Fatty Acids, Nonesterified / Q000378:metabolism; D005990:Glycerol / Q000378:metabolism; D007328:Insulin / Q000494:pharmacology*; D008066:Lipolysis / Q000187:drug effects / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D014280:Triglycerides / Q000378:metabolism
chemical_list: D004040:Dietary Carbohydrates; D004041:Dietary Fats; D005230:Fatty Acids, Nonesterified; D007328:Insulin; D014280:Triglycerides; D005990:Glycerol; D004837:Epinephrine