Brain Adipocytokine Action and Metabolic Regulation
- 1Division of Endocrinology, Diabetes and Metabolism, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania
- 2Children’s Hospital of Philadelphia, Philadelphia, Pennsylvania
- 3Department of Cell Biology and Diabetes Research and Training Center, Albert Einstein College of Medicine, Bronx, New York
- Address correspondence and reprint requests to Rexford S. Ahima, MD, PhD, University of Pennsylvania School of Medicine, Division of Endocrinology, Diabetes and Metabolism, 764 Clinical Research Building, 415 Curie Blvd., Philadelphia, PA 19104. E-mail: ahima{at}mail.med.upenn.edu
Abstract
Adipose tissue secretes factors that control various physiological systems. The fall in leptin during fasting mediates hyperphagia and suppresses thermogenesis, thyroid and reproductive hormones, and immune system. On the other hand, rising leptin levels in the fed state stimulate fatty acid oxidation, decrease appetite, and limit weight gain. These divergent effects of leptin occur through neuronal circuits in the hypothalamus and other brain areas. Leptin also regulates the activities of enzymes involved in lipid metabolism, e.g., AMP-activated protein kinase and stearoyl-CoA desaturase-1, and also interacts with insulin signaling in the brain. Adiponectin enhances fatty acid oxidation and insulin sensitivity, in part by stimulating AMP-activated protein kinase phosphorylation and activity in liver and muscle. Moreover, adiponectin decreases body fat by increasing energy expenditure and lipid catabolism. These effects involve peripheral and possibly central mechanisms. Adipose tissue mediates interconversion of steroid hormones and secretes proinflammatory cytokines, vasoactive peptides, and coagulation and complement proteins. Understanding the actions of these “adipocytokines” will provide insight into the pathogenesis and treatment of obesity and related diseases.
- ACC, acetyl-CoA carboxylase
- AgRP, agouti-related peptide
- AMPK, AMP-activated protein kinase
- CART, cocaine- and amphetamine-regulated transcript
- HGP, hepatic glucose production
- MCH, melanin concentrating hormone
- NPY, neuropeptide Y
- POMC, proopiomelanocortin
- WAT, white adipose tissue
Footnotes
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This article is based on a presentation at a symposium. The symposium and the publication of this article were made possible by an unrestricted educational grant from Servier.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
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- Accepted May 16, 2006.
- Received April 18, 2006.
- DIABETES
