Leptin Gives Itself Some Negative Feedback

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.