Dichotomous roles of leptin and adiponectin as enforcers against lipotoxicity during feast and famine.
Science is marked by the death of dogmas; the discovery that adipocytes are more than just lipid-storing cells but rather produce potent hormones is one such example that caught physiologists by surprise and reshaped our views of metabolism. While we once considered the adipocyte as a passive storage organ for efficient storage of long-term energy reserves in the form of triglyceride, we now appreciate the general idea (once a radical one) that adipocytes are sophisticated enough to have potent endocrine functions. Over the past two decades, the discoveries of these adipose-derived factors ("adipokines") and their mechanistic actions have left us marveling at and struggling to understand the role these factors serve in physiology and the pathophysiology of obesity and diabetes. These hormones may serve an integral role in protecting nonadipose tissues from lipid-induced damage during nutrient-deprived or replete states. As such, adipocytes deliver not only potentially cytotoxic free fatty acids but, along with these lipids, antilipotoxic adipokines such as leptin, adiponectin, and fibroblast growth factor 21 that potently eliminate excessive local accumulation of these lipids or their conversion to unfavorable sphingolipid intermediates.
Touchstone Diabetes Center, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75390-8549 Department of Cell Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390-8549.
Roger H
RH
Unger
Philipp E
PE
Scherer
William L
WL
Holland
D017667:Adipocytes / Q000378:metabolism* / Q000473:pathology; D052242:Adiponectin / Q000378:metabolism*; D000273:Adipose Tissue / Q000378:metabolism; D000818:Animals; D004734:Energy Metabolism; D005346:Fibroblast Growth Factors / Q000378:metabolism; D006706:Homeostasis; D020738:Leptin / Q000235:genetics / Q000378:metabolism*; D050356:Lipid Metabolism; D013217:Starvation / Q000378:metabolism* / Q000503:physiopathology
D052242:Adiponectin; D020738:Leptin; C414620:fibroblast growth factor 21; D005346:Fibroblast Growth Factors