Digging Deeply in Genetics to Grasp Obesity

At the Boston Course in Obesity Medicine, Sadaf Farooqi received the George L. Blackburn Foundation Award and delivered a masterclass of digging deeply into genetics to fully understand obesity. Simultaneously, she co-authored striking new observations about one dimension of this in the New England Journal of Medicine. All in a day’s work for someone intent upon really understanding the biology of obesity.

Environment or Genetics?

Paul Franks wrote recently in Diabetes Care that “the once-prevailing notion that human characteristics are the consequence of either genes or environment has been replaced.” Obesity and its rising prevalence is all about our genes interacting with a changing environment. It’s not either/or; it’s both genes and environment that matter. The research Franks is reflecting upon tells us the environment that matters is much broader than the food environment. A broad array of social and economic factors come into play and interact with the genetic susceptibility of individuals, as Sarah Cromer and colleagues showed. With favorable conditions, the risk of disease can come down by as much as 50 percent.

Erik Hemmingsson and colleagues recently wrote in Obesity Reviews that different forms of chronic social adversity can interact with genetic predisposition to explain a great deal of obesity development.

Folks who prefer single-point explanations – pointing fingers at the food industry – want no part of this. One of them told us recently there’s “no evidence for such a thing” as diverse causes of higher obesity prevalence beyond the rise of ultra-processed foods. But still, we have our doubts that taxing the foods economically stressed people tend to eat will lead them to better choices and better health.

Digging Deeply into the Genetics of Obesity

So in a seemingly very different world, Farooqi and her colleagues dig deeply to understand the genetics of obesity. Her paper in NEJM yesterday describes, for the first time, a mechanism of antagonism for the activity of leptin that produced severe obesity in two children whose hunger could not be satisfied. Discovering that mechanism permitted the reversal of their obesity and the attainment of near normal weight for them.

But this requires curiosity. It requires admitting that we don’t know everything we need to overcome obesity. So we are grateful for the scientific curiosity of Sadaf Farooqi and hope for many more to follow her example.

Click here for the new paper in NEJM, here for an editorial about it, here for the Franks commentary, here for the Cromer paper, and here for the Hemmingsson paper. For further excellent reporting on the new paper in NEJM, click here.

Lee Kaplan Presents the Blackburn Foundation Lecture Award to Sadaf Farooqi, photograph by Gitanjali Srivastava

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June 16, 2023