The fascinating reason some people can eat whatever they want and not gain weight

By and large, we attribute the ability to maintain a slim figure to a youthful metabolism. Metabolism certainly plays a role in weight regulation, but it might frustrate you to learn that some people are simply genetically predisposed to pig out regularly and still be thin. 

A new pioneering study published in the journal Cell has identified a gene called anaplastic lymphoma kinase (ALK) that may contribute to “thinness.”

“There is considerable inter-individual variability in susceptibility to weight gain despite an equally obesogenic environment in large parts of the world,” the authors wrote in the new report.  “Mechanistically, we found that ALK expression in hypothalamic neurons controls energy expenditure via sympathetic control of adipose tissue lipolysis. Our genetic and mechanistic experiments identify ALK as a thinness gene, which is involved in the resistance to weight gain.”

Identification of ALK in Thinness

The authors derived their initial hypothesis from over 47,000 participants from The Republic of Estonia.

After employing genome-wide association studies that essentially compared the genetic material of thin individuals and individuals of average weight,  the data revealed ALK as a recurring agent in the former. 

Although the gene had hitherto been mostly associated with various forms of cancer, the researchers suspected ALK might influence energy expenditure and consequently one’s ability to maintain their weight.  

To test this, the team deactivated the ALK genes in a crop of mouse models. Despite adhering to the same diet and exercise regimen as the control group, the mice with decreased ALK expression immediately became skinnier. Alk mutant mice appeared to exhibit a unique resistance to diet- and leptin-mutation-induced obesity

The experiment was successfully replicated with fruit fly models. 

“By using a technique called indirect calorimetry, we could show that ALK-deficient mice exhibit increased energy expenditure. This means that they burn more calories than normal mice and explains why they remain thin even if they eat the same amount of food. In addition to that, these animals also show improved glucose tolerance,” explains first author Michael Orthofer in a media release.

These findings pose particular relevance in the cracks where a pandemic and an obesity crisis collide. Reducing mortalities related to either will likely follow a better academic understanding of the mechanics driving them alongside changes in lifestyle. 

The idea that weight control may owe a great deal to biological predispositions is a powerful one. If stigmas around poor dieting dissolve it may give those who struggle with them an incentive to appreciate clinical solutions to the problem. 

“This strengthens the notion that ALK is indeed part of a larger brain circuit involved in energy expenditure. We are very excited about these results on the genetics of thinness and will further investigate the mechanisms of how ALK-expressing neurons are able to control weight. Our results also highlight the important therapeutic potential of ALK inhibition,” concludes Josef Penninger, IMBA group leader and founding director & director of the Life Sciences Institute of the University of British Columbia.

CW Headley is a reporter for the Ladders and can be reached at cheadley@theladders.com