Regulation of energy balance and carbohydrate/lipid metabolism

Regulation of energy balance and carbohydrate/lipid metabolism

10 Pages · 2003 · 182 KB · English

Section IV: Lipid Modulators of Islet Function. Update on Adipocyte Hormones. Regulation of Energy Balance and Carbohydrate/Lipid. Metabolism. Peter J. Havel .. and more numerous adipocytes than women with android fat distribution (124) Dev Cell 3:25–38, 2002. 2. Bluher M, Kahn BB, Kahn 

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UC Davis UC Davis Previously Published Works Title Update on adipocyte hormones Regulation of energy balance and carbohydrate/lipid metabolism Permalink https://escholarshiporg/uc/item/2q36655k Author Havel, Peter J, DVM, PhD Publication Date 20040201 Peer reviewed eScholarshiporg Powered by the California Digital Library University of California Section IV: Lipid Modulators of Islet Function Update on Adipocyte Hormones Regulation of Energy Balance and Carbohydrate/Lipid Metabolism Peter J Havel Hormones produced by adipose tissue play a critical role in the regulation of energy intake, energy expenditure, and lipid and carbohydrate metabolism This review will address the biology, actions, and regulation of three adi pocyte hormones—leptin, acylation stimulating protein (ASP), and adiponectin—with an emphasis on the most recent literature The main biological role of leptin ap pears to be adaptation to reduced energy availability rather than prevention of obesity In addition to the wellknown consequences of absolute leptin deciency, subjects with heterozygous leptin gene mutations have low circulating leptin levels and increased body adiposity Leptin treatment dramatically improves metabolic abnor malities (insulin resistance and hyperlipidemia) in pa tients with relative leptin deciency due to lipoatrophy Leptin production is primarily regulated by insulinin duced changes of adipocyte metabolism Dietary fat and fructose, which do not increase insulin secretion, lead to reduced leptin production, suggesting a mechanism for highfat/highsugar diets to increase energy intake and weight gain ASP increases the efciency of triacylglycerol synthesis in adipocytes leading to enhanced postprandial lipid clearance In mice, ASP deciency results in reduced body fat, obesity resistance, and improved insulin sensi tivity Adiponectin production is stimulated by thiazo lidinedione agonists of peroxisome proliferatoractivated receptorand may contribute to increased insulin sensi tivity Adiponectin and leptin cotreatment normalizes in sulin action in lipoatrophic insulinresistant animals These effects may be mediated by AMP kinase–induced fat oxidation, leading to reduced intramyocellular and liver triglyceride content The production of all three hormones is inuenced by nutritional status These hormones, the pathways controlling their production, and their receptors are promising targets for managing obesity, hyperlipid emia, and insulin resistanceDiabetes53 (Suppl 1): S143–S151, 2004 A dipose tissue plays a crucial role in the regula tion of energy homeostasis, insulin sensitivity, and lipid/carbohydrate metabolism These ac tions are mediated by both the actions of a number of nonsecreted proteins and hormones produced in adipocytes A recent example of the importance of adipocyte function to have profound systemic effects is provided by the report that mice speci?cally lacking insulin signaling in adipocytes (FIRKO mouse) are not only lean, leptin sensitive, and obesity resistant (1), but live almost 20% longer than wildtype control animals (2) Adipocytes produce a number of hormones that have wideranging effects on energy intake, energy expenditure, and carbohydrate and lipid metabolism, including nutrient partitioning and fuel selection Work in our laboratory has primarily focused on the biology and regulation of three key adipocyte hormones: leptin, acylationstimulating pro tein, and adiponectin A review examining the role of these three hormones in regulating energy homeostasis and insulin action was published in early 2002 The purpose of the present review is to summarize the most important aspects of the biology, actions, and regulation of these hormones and to serve as an update of new information published during the past18 months LEPTIN Because the biology of leptin, including its role in energy balance and the regulation of its production, has been reviewed in detail (3,4), this section will primarily concen trate on more recent ?ndings not covered in previous reviews Importantly, recent data indicate that the effects of leptin to inhibit food intake are mediated by signaling through phosphatidylinositol 3kinase (5), which is shared by the insulin signal transduction pathway This pathway is therefore likely to mediate common actions of insulin and leptin as peripheral signals to the central nervous system (CNS) in the hypothalamic regulation in eating behavior and metabolic homeostasis (3,6,7) Another study implicated inhibition of liver steroyl CoA desaturase as a mechanism mediating some of the metabolic effects of leptin, particularly with regard to hepatic lipid metabolism (8) Leptin deciency and leptin treatmentIt is now apparent that the primary importance of leptin in the From the Department of Nutrition, University of California, Davis, Davis, California Address correspondence and reprint requests to Peter J Havel, DVM, Department of Nutrition, University

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