Feast or famine: Researchers identify leptin receptor’s sidekick as a target for appetite regulation

A Mayo Clinic researcher says the surprising findings suggest the possibility of a novel treatment for obesity

JACKSONVILLE, Fla. - Friday, January 28th 2011 [ME NewsWire]

(BUSINESS WIRE)-- A study by researchers at Mayo Clinic’s campus in Floridaand Washington University School of Medicine adds a new twist to the body of evidence suggesting human obesityis due in part to genetic factors. While studying hormone receptors in laboratory mice, neuroscientists identified a new molecular player responsible for the regulation of appetite and metabolism.

In the Jan. 11 online issue of PLoS Biology, the authors report that mice engineered not to express the lipoprotein receptor LRP1, in the brain’s hypothalamus, began to eat uncontrollably, growing obese as well as lethargic. They found that LRP1, a major transporter of lipids and proteins into brain cells, is a “co-receptor” with the leptin receptor -- meaning that both the leptin and LRP1 receptors need to work together to transmit leptin signals.

Leptin decides whether fat should be stored or used, resulting in lethargy or energy. When working properly, the hormone, which is made when body cells take in fat from food, travels to the brain to tamp down appetite.

“If a person is born with too little gene expression in the leptin pathway, which includes its receptors, or the circuitry is not functioning well, then leptin will not work as well as it should,” says the study’s lead investigator, neuroscientist Guojun Bu, Ph.D., of Mayo Clinic. “Appetite will increase, and body fat will be stored.”

Given these results, Dr. Bu says it may be possible to develop a treatment that increases gene expression in one or both of the protein receptors, which then increases the messages meant to decrease appetite sent to the brain.

The study was funded by the National Institutes of Health and the Alzheimer’s Association.

The researchers declare no conflicts of interest.

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