Digging Deeply into the Personal Molecular Basis of Obesity

One of the hottest concepts in obesity is precision medicine. That’s especially important because obesity is different in every person who experiences it. One person might respond beautifully to a given treatment. Then that same treatment will have disappointing effects in the next person. So it’s exciting to see new landmark research in Cell Systems that gives us a glimpse into the molecular basis for these differences.

Applying Multiple Omics Technologies

Brian Piening and a large team of scientists applied a wide range of advanced biotechnologies in their study of weight gain and loss.

Without these technologies, it’s plain enough that two people might have a similar degree of obesity, but be very different. But the problem has been to understand those differences. Multiple omics technologies open the door to digging deeper.

Piening et al probed deeply into the biology of 23 individuals. Genomics, transcriptomics, proteomics, metabolomics, and microbiomics provided detailed profiles of their individual molecular biology. They measured profiles at baseline, during weight gain, and then during weight loss to return to baseline.

They found markers for inflammation and heart disease during weight gain. Some of the profiles returned to normal after weight loss and some did not. And they found highly personalized differences in these markers among the individuals in these studies. But perhaps most interesting are the profiles that distinguish insulin resistance. These might find a role in better diagnosis.

Pointing the Way to Personalized Care for Obesity

As ambitious as this study was, it is only a start. These researchers made literally millions of measurements in a small group of people and their microbiomes. Even so, the authors say, “We are likely a long way from a complete omic representation of complex human biochemical systems.”

Writing in JAMA recently, Jack and Susan Yanovsky explained the need for precision approaches to obesity:

Even under obesity-promoting conditions, not everyone develops obesity; there is variability
in response to the environment. Important differences among individuals in obesity susceptibility may be due to psychosocial, cultural, and economic factors, but also can be caused by genetic sequence variations, epigenetic events, and other factors, including gene-environment interactions.

We may be on the cusp of a much deeper understanding of why some people develop obesity when others do not. Perhaps we can find why people respond so differently to the same treatments. Such knowledge holds promise for better, more precise treatment. It holds the promise for better prevention strategies.

Eat-less, move-more thinking seems quaint by comparison.

Click here for the study in Cell Systems and here for more on omics-based strategies for precision medicine.

Which Molecule? Photograph © jacki-dee / flickr

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January 22, 2018