Leptin and the OB Gene: A Toehold for Obesity Science

More than 20 years ago, discovery of the ob (obesity) gene and the protein that it encodes – leptin – was a breakthrough for obesity science. Mice that lack the gene develop extreme obesity. And giving them the protein reverses it. Some people misleadingly dubbed it a satiety hormone. In Cell Metabolism, a new commentary by Jeffrey Flier and Eleftheria Maratos-Flier points out that many gaps remain in evidence base about this gene.

Not Really a Satiety Hormone

Flier describes the thinking that leads to this misleading label:

Since its discovery, it has also been hypothesized that rising leptin levels caused by overfeeding provide a physiologic signal that orchestrates resistance to obesity. Although still widely believed, and possibly true in some circumstances, this aspect of leptin physiology has not been experimentally demonstrated.

Michael Rosenbaum, an early and prolific researcher on leptin, tells us that this thinking is incorrect:

We have said from the beginning that leptin’s primary function is to alert energy homeostastic systems when weight stores (fat) are too low or energy balance (intake – output) is too low and not to prevent obesity. The idea that leptin’s primary function is to promote weight loss rather than to protect fat stores makes no evolutionary sense.

In truth, the ob gene and leptin’s discovery provided an important toehold for obesity science. It proved to be a starting point for understanding the complex mechanisms that regulate fat stores. And this protein may have a role to play in maintaining a reduced weight. But without further research, we will never know.

And Flier is correct that much unfinished work remains to understand its function fully. Scientific curiosity is the cure for obesity. Let’s take a big dose.

Click here for the commentary and here for further perspective from Harvard Medical School.

Rock Climbing 3, photograph © Eugene Soltan / flickr

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July 5, 2017