Control of energy homeostasis and insulin action by adipocyte hormones: leptin, acylation stimulating protein, and adiponectin

By P. Havel. Current Opinion in Lipidology, 2002

631 citations recorded by the source corpus.

&NA; Adipose tissue performs complex metabolic and endocrine functions. This review will focus on the recent literature on the biology and actions of three adipocyte hormones involved in the control of energy homeostasis and insulin action, leptin, acylation‐stimulating protein, and adiponectin, and mechanisms regulating their production. Results from studies of individuals with absolute leptin deficiency (or receptor defects), and more recently partial leptin deficiency, reveal leptin's critical role in the normal regulation of appetite and body adiposity in humans. The primary biological role of leptin appears to be adaptation to low energy intake rather than a brake on overconsumption and obesity. Leptin production is mainly regulated by insulin‐induced changes of adipocyte metabolism. Consumption of fat and fructose, which do not initiate insulin secretion, results in lower circulating leptin levels, a consequence which may lead to overeating and weight gain in individuals or populations consuming diets high in energy derived from these macronutrients. Acylation‐stimulating protein acts as a paracrine signal to increase the efficiency of triacylglycerol synthesis in adipocytes, an action that results in more rapid postprandial lipid clearance. Genetic knockout of acylation‐stimulating protein leads to reduced body fat, obesity resistance and improved insulin sensitivity in mice. The primary regulator of acylation‐stimulating protein production appears to be circulating dietary lipid packaged as chylomicrons. Adiponectin increases insulin sensitivity, perhaps by increasing tissue fat oxidation resulting in reduced circulating fatty acid levels and reduced intramyocellular or liver triglyceride content. Adiponectin and leptin together normalize insulin action in severely insulin‐resistant animals that have very low levels of adiponectin and leptin due to lipoatrophy. Leptin also improves insulin resistance and reduces hyperlipidemia in lipoatrophic humans. Adiponectin production is stimulated by agonists of peroxisome proliferator‐activated receptor‐gamma; an action may contribute to the insulin‐sensitizing effects of this class of compounds. The production of all three hormones is influenced by nutritional status. These adipocyte hormones, the pathways controlling their production, and their receptors represent promising targets for managing obesity, hyperlipidemia, and insulin resistance.

Subfields: Endocrine and Autonomic Systems, Epidemiology, Physiology

View Paper: https://www.semanticscholar.org/paper/5c440e3e0a159aaf01531b74c1ee35bf09113f62

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Endocrine and Autonomic Systems

1. P. Havel
2. Matthias Tschöp
3. E. Ravussin
4. L. Heilbronn
5. M. Heiman
6. Barry M. Popkin
7. Roger Cone

In Epidemiology

1. Barry M. Popkin
2. E. Ravussin
3. L. Heilbronn
4. G. Bray
5. S. Nielsen
6. N. Keim
7. Sharon S Elliott
8. K. Teff

In Physiology

1. P. Havel
2. Barry M. Popkin
3. Matthias Tschöp
4. E. Ravussin
5. L. Heilbronn
6. M. Heiman
7. G. Bray
8. S. Nielsen

Citations in the corpus

• Dietary fructose: implications for dysregulation of energy homeostasis and lipid/carbohydrate metabolism. (2005, background): “Insulin increases leptin gene expression and leptin secretion, and is the dominant physiological signal in the regulation of leptin production and its diurnal pattern.(153) Infusion of insulin at rates producing physiological increases of plasma insulin levels stimulates circulating leptin with a ti”
• Dietary fructose reduces circulating insulin and leptin, attenuates postprandial suppression of ghrelin, and increases triglycerides in women. (2004, background): “Because insulin and leptin function as key signals conveying information on energy intake and body fat stores to the central nervous system (CNS) for the long-term regulation of food intake and energy homeostasis (3, 4), it is possible that reduced insulin and leptin production contributes to increa”
• Fructose, weight gain, and the insulin resistance syndrome. (2002, background): “Together, the available evidence strongly suggests an important role for leptin in the regulation of energy balance in humans (11, 62).”
• Adiponectin expression from human adipose tissue: relation to obesity, insulin resistance, and tumor necrosis factor-alpha expression. (2003, background): “have implicated adipose tissue TNF- , IL-6, and leptin in obesity-related insulin resistance (23,28).”
• Smoking cessation and weight gain (2004, background): “Adiponectin has an anti-inflammatory effect on endothelial cells, inhibits the proliferation of vascular smooth muscle cells and suppresses the conversion of macrophages to foam cells (52).”
• Adiponectin promotes adipocyte differentiation, insulin sensitivity, and lipid accumulation Published, JLR Papers in Press, April 16, 2005. DOI 10.1194/jlr.M400373-JLR200 (2005, background): “energy expenditure, and carbohydrate and lipid metabolism (1).”
• Relationship of adiponectin to body fat distribution, insulin sensitivity and plasma lipoproteins: evidence for independent roles of age and sex (2003, background): “Finally, a reduction in adiponectin concentrations would be anticipated to impair insulin action in the peripheral tissues resulting in less efficient glucose uptake and the deposition of triglyceride in the muscle [27].”
• Calorie restriction and aging: review of the literature and implications for studies in humans. (2003, background): “Adipocytes secrete numerous cytokines that can affect substrate oxidation, EE, insulin sensitivity, and the neuroendocrine system (33).”
• Consumption of high-fructose corn syrup in beverages may play a role in the epidemic of obesity. (2004, background): “In addition, insulin may modify food intake by its effect on leptin secretion, which is mainly regulated by insulin-induced changes in glucose metabolism in fat cells (19, 20).”
• The lipid kinase PI5P4Kβ is an intracellular GTP sensor for metabolism and tumorigenesis (2016, neutral): “188 Molecular Cell 61, 187–198, January 21, 2016 a2016 Elsevier Inc amount of GTP is required in rapidly dividing cells, such as tumor cells, and tissues producing serum proteins, such as the liver, pancreas, and adipose tissue (Caro and Palade, 1964; Havel, 2002; Ma and Blenis, 2009; Miller et al.,”
• TNF-α Is a Predictor of Insulin Resistance in Human Pregnancy (2002, background): “Recently, investigators have focused on several new potential mediators of insulin resistance including the cytokine tumor necrosis factor (TNF)- , the anti-obesity hormone leptin, and adipose-derived resistin, adiponectin, and free fatty acids (10,11).”