Maybe obesity is not about having an obesity gene. Maybe it’s about not having a thinness gene. Also blaming the obesity epidemic on too much good/bad food and not enough exercise in your environment has to reconcile the fact that some few of us are still staying skinny. Not me.
Using a uniquely catalogued DNA bank and physical data set of a large number of Estonians (Estonian Genome Center University of Tartu, EGCUT), scientists have discovered anaplastic lymphoma kinase (ALK) as a candidate thinness gene. By data mining this large genome-wide association catalog of studies of this Estonian cohort and comparing the fattest and skinniest 2% of them they showed that several variants of the ALK gene were associated with different metabolic traits such as thinness, BMI, and lipid and glucose control. Anaplastic lymphoma kinase is called that because it is frequently mutated in various types of cancer and has been studied in the past in this regard. But it must be multi-talented.
So first they tried knocking out this gene in fruit flies. That lowered their levels of triglycerides but not much else. Then the ALK gene was knocked out in mice. These ALK knockout mice were thin, had improved blood sugar control and increased energy expenditure while having unaltered food intake and activity. Furthermore these investigators were able to discover that these effects of lacking ALK were caused by actions in the brain but not the liver or fat or muscle cells. But that’s no ALK. There must be variations in present ALK that don’t do some things.
So starting with Estonian statistics and then manipulating this ALK connection in bugs and mice we might be able to get an understanding that would help even non-Estonian humans someday.
1. Orthofer et al., Identification of ALK in Thinness, Cell (2020), https://doi.org/10.1016/j.cell.2020.04.034
This writer’s opinion is their own and not the opinion of this newspaper
John DiTraglia M.D. is a Pediatrician in Portsmouth. He can be reached by e-mail- firstname.lastname@example.org or phone-354-6605.