Leptin is an important regulator of the amount of fuel that our bodies store. It acts in the brain to tell the body that fuel stores have been restocked and that it can stop feeding. Many individuals who are obese exhibit leptin resistance, that is, they do not respond appropriately to high levels of leptin in their blood. One possible cause of leptin resistance is that leptin only poorly activates the leptin receptor (LRb).
In a study that appears online on April 5 in advance of publication in the May print issue of the Journal of Clinical Investigation, Martin Myers and colleagues from the University of Michigan, Ann Arbor, used mice expressing a mutant form of LRb to characterize a leptin-mediated LRb signaling pathway that inhibits further leptin-mediated LRb signaling.
Female mice, but not male mice, expressing only forms of LRb in which a single amino acid, tyrosine 985, had been mutated weighed less than normal mice, did not become obese when fed a high-fat diet, ate less, and produced lower amounts of neuropeptides that stimulate appetite. In addition, these female mice were more sensitive to leptin administration than wild-type female mice.
These data indicate that leptin-mediated signaling through LRb tyrosine 985 inhibits leptin-mediated LRb signaling in female mice. The authors therefore propose that this negative feedback pathway might contribute to leptin resistance in some obese individuals, in particular females.
Materials provided by Journal of Clinical Investigation. Note: Content may be edited for style and length.
Cite This Page: