A role for dietary fat in leptin receptor, OB-Rb, function.
Leptin is a hormone believed to control appetite and regulate body weight via receptors in the hypothalamus. Much is known about the structure of the functional, or long, form of the leptin receptor, OB-Rb. However, the mechanism by which the receptor regulates leptin's biological action is unknown. Both the type and amount of dietary fat have been shown to affect factors involved in OB-Rb binding and signaling, as well as the morphology of hypothalamic cell membranes. Thus, the following review article examines possible mechanisms by which dietary fat may affect OB-Rb functioning at the hypothalamic level. Dietary fat can alter the fatty acid make-up of membranes, such as the polyunsaturated:saturated fat ratio, changing membrane fluidity and possibly leading to an enhancement or impairment of the structure and/or function of any membrane-associated receptor complexes. Dietary fat also interferes in biochemical pathways involving leptin, OB-Rb, and other neurons containing neuropeptides under OB-Rb's control, such as neuropeptide Y (NPY), proopiomelanocortin (POMC), and cocaine- and amphetamine-regulated transcript (CART). Increased monounsaturated fat increases cyclic adenosine monophosphate (cAMP) levels, possibly reducing mitogen-activated protein kinase (MAPK) activation and interrupting leptin signaling through Janus kinase/signal tranducers and activators of transcription (JAK/STAT) pathways. Dietary induced alterations in hypothalamic cell membranes, SNS activity, or other factors involved in OB-Rb function form a possible basis for the control of leptin's effects on body composition and appetite. Improving the biological activity of leptin by diet modification may exist as a practical strategy for the treatment of obesity and related disorders.
Heshka
J T
JT
School of Dietetics and Human Nutrition, McGill University, Ste-Anne-de-Bellevue, Quebec, Canada.
Jones
P J
PJ
D000818:Animals; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D004041:Dietary Fats / Q000378:metabolism*; D006801:Humans; D007031:Hypothalamus / Q000378:metabolism; D008024:Ligands; D020033:Protein Isoforms; D011956:Receptors, Cell Surface; D018121:Receptors, Cytokine / Q000235:genetics / Q000378:metabolism*; D054411:Receptors, Leptin; D015398:Signal Transduction
D002352:Carrier Proteins; D004041:Dietary Fats; C515448:LEPR protein, human; D008024:Ligands; D020033:Protein Isoforms; D011956:Receptors, Cell Surface; D018121:Receptors, Cytokine; D054411:Receptors, Leptin