The Tangled Garden

Untangling the Metabolic Effects of Higher Adiposity

We are pretty much done with the label of healthy obesity, because it is a perfect oxymoron. If a pattern of adiposity is healthy, then it’s not obesity. But newly published in eLife is a more thoughtful approach to this subject. This study seeks to untangle the metabolic effects of higher adiposity from other effects that it might have. Susan Martin and colleagues have used Mendelian randomization to understand the metabolic effects of adiposity.

Obesity ComplicationsThey found 11 diseases likely caused by metabolic consequences of high adiposity. They also found nine diseases that arise from non-metabolic effects of adiposity. Through careful work, Martin et al describe the genetic basis for obesity with and without metabolic complications.

Apparently, some genes offer a degree of protection against the metabolic effects of obesity.

Drawing on Large Sources of Genetic Data

Martin et al used data from 28 GWAS publications, FinnGen, and the UK BioBank. They analyzed 37 chronic diseases linked to obesity and genetic variants that link them. Thus, they found genetic variants associated with metabolically favorable (FA) and unfavorable (UFA) adiposity.

Then, using Mendelian randomization, they narrowed the list of 37 diseases linked to obesity to 20 for which their evidence suggested a causal link. Of those, 11 came from the metabolic fallout of high adiposity. Nine came from other effects.

Metabolic and Other Harms of Obesity

So in a very elegant way, Martin has teased out the metabolic harms of obesity from some of its other pathologies. They explain:

Our results assist in understanding the consequences of higher adiposity uncoupled from its adverse metabolic effects, including the risks to individuals with high body mass index who may be relatively metabolically healthy.

Overall, Martin’s findings can add to our understanding the biological basis of obesity. It is a highly heritable condition, but many people recoil from that idea. The retort that genes are not destiny is true enough. Nonetheless, it’s essential to know what you’re dealing with in any health condition. Obesity is no different. Biology is at the root of it.

Click here for the study by Martin et al and here for further reporting from Medscape. For additional perspective from the lead author, click here.

The Tangled Garden, painting by J. E. H. MacDonald / WikiArt

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February 3, 2022

3 Responses to “Untangling the Metabolic Effects of Higher Adiposity”

  1. February 03, 2022 at 11:26 am, David Brown said:

    We are pretty much done with the label of healthy obesity, because it is a perfect oxymoron. If a pattern of adiposity is healthy, then it’s not obesity.

    Actually, there is a pattern of obesity that is associated with less risk for chronic inflammatory disease and complications associated with viral infections. Two articles about the so-called obesity paradox:

  2. February 03, 2022 at 12:00 pm, John DiTraglia said:

    I think this says that obesity, separate from it’s metabolic associations and the mechanical stress on the knees and the cosmetic and discrimination issues, is not a disease, in the same way that being black is not a disease.

  3. February 03, 2022 at 2:17 pm, Katherine Flegal said:

    I don’t fully understand this complicated study, but looking at the acknowledgements, I was struck that they seem to include a lot of studies with self-reported weight and height data, including the American Cancer Society Nutrition II study and the Harvard data sets from the Nurses Health Study, and the physicians and health care professionals studies. I wonder how these self-reported data were used.