UBC researcher helps identify human gene that controls thinness

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      A UBC biomedical researcher is part of a scientific team that has identified a human gene that appears to control thinness.

      Josef Penninger, the director of UBC's Life Sciences Institute and a professor in the department of medical genetics, is the senior author of a paper published on May 21 in the journal Cell that explains how a particular gene caught the team's attention during a study of thinness.

      Further research on the gene revealed that it appears to play a role in resisting weight gain.

      Genes are the physical units that are the basis for heredity. They are made up of DNA—a molecule that contains genetic instructions—and are found in chromosomes in our cell nuclei. Genes therefore constitute a set of instructions that determine everything from our hair and eye colour to our physical development to our reproduction.

      Josef Penninger
      Wikipedia/Annabelle Penninger

      Penninger, who is also a Canada 150 research chair, said in a May 21 UBC release that the study was a reversal of the usual scientific inquiries into obesity: "We all know these people who can eat whatever they want; they don’t exercise, but they just don’t gain weight. They make up around one percent of the population.

      "We wanted to understand why,” Penninger said. “Most researchers study obesity and the genetics of obesity. We just turned it around and studied thinness, thereby starting a new field of research."

      The study utilized data from an Estonian biobank that featured the genetic makeups of 47,102 healthy and thin (or normal weight) individuals between the ages of 20 and 44.

      In that thin group, the research team—which included scientists from Australia, Switzerland, and Austria—looked for variations in the genetic profiles and found one: a mutation in the gene called anaplastic lymphoma kinase (ALK).


      Although ALK's function in humans is not well understood, it is known to mutate in some cancers and is involved in tumour development. When the researchers took the ALK gene out of flies and mice in lab trials, the subjects were resistant to obesity during induced diets.

      Mice that had no ALK gene weighed less and had less body fat than those that had the gene, even though they ate the same diet and exercised the same amount.

      Michael Orthofer, the paper's lead author and a postdoctoral fellow at Vienna's Institute of Molecular Biology, said in the release that the gene in question worked outside of the digestive system. "Our work reveals that ALK acts in the brain, where it regulates metabolism by integrating and controlling energy expenditure," Orthofer explained.

      UBC's Penninger noted possible future research to determine how ALK might regulate human metabolism to encourage thinness.

      "It’s possible that we could reduce ALK function to see if we did stay skinny,” Penninger said. “ALK inhibitors are used in cancer treatments already, so we know that ALK can be targeted therapeutically."