Obesity Causes: Physiology, Genes, and Signals

BridgeYesterday was the first of three days exploring the best scientific thinking in the world on the causes of obesity. From the start, it was plain that obesity presents a puzzle. Physiology, genes, and signals regulate the storage of energy in adipose tissue and thus obesity. But one thing was clear after 12 scientists through the day described the most advanced research aimed at making sense of this puzzle. Many questions remain unresolved.

Simple Metrics Fail

This seemingly simple condition – unhealthy adiposity – is not just a simple problem of size and weight. Yet the scientific tools for quantifying obesity fall short of the precision needed to really understand this heterogeneous disease. Professor Ruth Loos explained this at the beginning of her presentation on genetic subtyping for obesity:

“Can we use these genetic markers to predict obesity? Even though we may believe that we can, the actual predictive ability is pretty poor – way, way not good enough to use in a clinical setting.

“Maybe the reasons for the overall limited success so far is because we study BMI most of the time – even though we know that some people have a very different body composition with the same BMI. Some people have very different risk for comorbidity.”

Diverse signals

So the role of genetics in obesity is far more complex than anyone imagined when discovery of the FTO gene opened the door to these insights. Marcelo Nóbrega explored how that discovery has led to a deeper appreciation of complexity of genetic influences on obesity. And it’s not just obesity that our genes influence. Sadaf Farooqi explained that thinness and resistance to weight gain also have a distinct genetic basis.

Though the brain seems to be the most important organ for regulating fat tissue, it doesn’t do it in isolation. Signaling between the brain and gut plays a role, as does the adipose tissue itself. Estrogens regulate the flow of signals between fat tissues, and so biological sex is a factor. In fact, Deborah Clegg tells us that sex influences all aspects of human metabolism.

We get further signals from our food and its ingredients. High fat and sugar diets can rewire dopamine circuits and thus prompt the development of obesity.

In sum, the range of signals that interact with our genes to govern the physiology of obesity is truly boggling. Thus, this summary barely scratches the surface of the rich information presented in the first day of this three-day event at the Royal Society.

So do yourself a favor and review each of the presentations from this first day. You’ll find all 12 of them here. For the background on this meeting, click here.

Bridge, painting by Joseph Stella / WikiArt

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October 18, 2022