Academia, Pre-clinical

A new avenue for diet pill makers? UC San Diego researchers uncover root of leptin resistance

Let’s be honest, the market for weight loss drugs has mostly been bust. While the industry has moved on from the fen-phen fiasco of decades past, newer diet pills like Belviq and Qsymia have still failed to deliver big sales. In the background, however, scientists continue to unpack the complicated internal mechanisms that lead to obesity. And a team of researchers in San Diego say they’ve discovered something that might give drugmakers renewed hope.

The news comes from a collection of researchers at the University of California San Diego (UCSD) who just published their findings in Science Translational Medicine. In short, they say they’ve uncovered a molecular mechanism that causes leptin resistance, a well-known phenomenon connected to obesity. In mice studies, they found a high-fat diet produced an enzyme named MMP-2. This enzyme goes around “clipping” the hormone receptors for leptin on the surface of neuronal cells. If the receptor is clipped, then leptin never binds to neuronal cells in the hypothalamus — meaning your brain never gets the signal that your belly is full and you should stop eating.

Credit: University of California San Diego


“We opened a new field of study for metabolic disease,” said Rafi Mazor, a research scientist at the UCSD and the paper’s first author. “We need to ask what other pathways, in addition to leptin and its receptors, undergo a similar destructive process and what the consequences might be.”

Rafi Mazor

Mazor is part of a team that includes other UCSD researchers, the Salk Institute for Biological Studies in La Jolla, Tel Aviv University in Israel, and Monash University in Australia.

The team is calling for a large-scale clinical trial to see if MMP-2 inhibitors might help people lose weight.

The study was led by Mazor and UCSD professor Geert Schmid-Schonbein, which you can see in full here.


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