Proteomics Tell Us Obesity Treatment Is More Than Weight Loss

The ongoing debate about the clinical definition of obesity is soon to get more intense. But already, it tells us pretty clearly that obesity is defined by more than excess weight. New research in Nature Medicine comes at this subject from an entirely different direction. Using proteomics, Lasse Maretty and colleagues find that the effects of obesity treatment with semaglutide go well beyond weight loss and glucose lowering.

Broad Effects

Proteomics is an intimidating word that simply means the study of proteins in quite a bit of detail. This includes their structure, function, and interactions with each other in the cells of organisms such as ourselves. Proteomics help with understanding the function of proteins in many different kinds of disease, including obesity.

Maretty et al analyzed proteomic data from placebo-controlled semaglutide studies in persons with obesity. That data provided unique perspective, leading them to conclude:

“We identified evidence supporting broad effects of semaglutide, implicating processes related to body weight regulation, glycemic control, lipid metabolism and inflammatory pathways. Several proteins were regulated with semaglutide, after accounting for changes in body weight and HbA1c at end of trial, suggesting effects of semaglutide on the proteome beyond weight loss and glucose lowering.

“A comparison of semaglutide with real-world proteomic profiles revealed potential benefits on disease-specific proteomic signatures including the downregulation of specific proteins associated with cardiovascular disease risk, supporting its reported effects of lowering cardiovascular disease risk and potential drug repurposing opportunities.”

More Than Weight

We don’t need a PhD in proteomics to understand that there is more to obesity than just a weight problem. But these data certainly tell us that obesity is disturbing the biochemistry of our body’s proteins. These effects tell us a lot about why other diseases result from obesity. They also give us a hint about why treating obesity with a powerful drug like semaglutide can have beneficial effects on so much more than weight.

Click here for the new study in Nature Medicine, here and here for further perspective on the effects of GLP-1 agonists beyond weight loss.

Human interactome, image by Keiono, licensed under CC BY-SA 3.0

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January 4, 2025