Molecular and anatomical determinants of central leptin resistance.
The increasing incidence of obesity in developed nations is an ever-growing challenge to health care, promoting diabetes and other diseases. The hormone leptin, which is derived from adipose tissue, regulates feeding and energy expenditure. Most forms of obesity are associated with diminished responsiveness to the appetite-suppressing effects of leptin. Here we review the mechanisms by which leptin activates intracellular signals, the roles of these signals in leptin action in vivo, and mechanisms that may attenuate leptin signaling, limiting its action in obese individuals. We highlight data regarding the expression of SOCS3 (a potential mediator of leptin resistance) in the arcuate nucleus of the hypothalamus.
Münzberg
Heike
H
Division of Metabolism, Endocrinology and Diabetes, Department of Medicine, University of Michigan Medical School, 1150 West Medical Center Drive, Ann Arbor, Michigan 48109, USA.
Myers
Martin G
MG
D000273:Adipose Tissue / Q000378:metabolism*; D000818:Animals; D001069:Appetite Regulation / Q000502:physiology*; D004734:Energy Metabolism / Q000502:physiology*; D006801:Humans; D007031:Hypothalamus / Q000378:metabolism / Q000503:physiopathology; D020738:Leptin / Q000378:metabolism*; D009765:Obesity / Q000378:metabolism / Q000503:physiopathology*; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism*; D054411:Receptors, Leptin; D012097:Repressor Proteins / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins; D014157:Transcription Factors / Q000378:metabolism
C515448:LEPR protein, human; D020738:Leptin; D011956:Receptors, Cell Surface; D054411:Receptors, Leptin; D012097:Repressor Proteins; C106644:SOCS3 protein, human; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins; D014157:Transcription Factors