Obesity: Gut Signals, Fat Tissue, and Bariatric Surgery

Self-Portrait with Cod's Head,Bariatric surgery has a profound effect on the chronic disease of obesity. Diabetes goes into remission and hunger recedes. Metabolism finds a steadier state, more compatible with good health. But the billion-dollar question is, how? Make no mistake. This is a big puzzle. Now a series of publications over the last several weeks reveals the role of some very particular signals between the gut and fat tissue in obesity. The signaling uses proteins known as hypoxia inducible factor – HIF. More specifically, this research is all about HIF-2α.

A Six-Year Journey

Randy Seeley tells us that he and an outstanding group of scientists have been on a journey to describe this pathway now for six years. They have found that higher activity of HIF-2α might explain reduced body fat after bariatric surgery. They’ve also seen relationships to better glucose tolerance, reduced liver fat, and increased GLP-1 secretion.

Remember that GLP-1 is a potent signal for regulating appetite and glucose metabolism. It’s the target of semaglutide, which is proving to be a major advance in obesity treatment.

What this work points to is another potential target for obesity treatment as researchers are reaching for drugs that can replicate the benefits of bariatric surgery without the surgery.

The Gut Is an Endocrine Organ

We know that the gut is an important endocrine organ that constantly trades signals with the brain and fat tissue to regulate metabolism. In obesity, these signals are off just enough to raise the set point for fat mass to a level that causes profound health problems over time. It appears that HIF-2α might be an important signal in this process. It may have a role in fat tissue inflammation and cardiac myopathy.

Through this outstanding work, scientific knowledge of the biological mechanisms that cause obesity is advancing. This knowledge equips scientists with leads for developing better treatments.

This excellent body of work on HIF-2α signals in the gut is one more piece in the very large puzzle of obesity becoming more complete day by day. At this point, the bias for denying the biological basis for obesity is looking like a quaint artifact. Those who continue to harbor it will become relics themselves as the science of obesity progresses.

Click here, here, and here to dive into these three fascinating publications.

Self-Portrait with Cod’s Head, painting by Edvard Munch / WikiArt

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January 21, 2022