Why Obesity Leads to Type 2 Diabetes

A novel protein linked to diabetes may help explain why most obese individuals develop insulin resistance and type 2 diabetes.

It has been previously demonstrated how the absence of the protein PTRF (Cavin-1) in humans and model organisms results in lipodystrophy, an almost complete loss of fat cells.

In a recent study published in eLife, researchers found that when there is a lack of fat cells, it causes the fat to be mis-targeted to other tissues, and results in it becoming insulin resistant, and eventually leads to type 2 diabetes. Paradoxically, a majority of obese individuals have an abundance of fat cells, but they end up developing insulin resistance, and their fat is also mis-targeting to other tissues.

For the study, researchers analyzed model organisms to compare them with models that lacked PTRF. They also studied lab-grown fat cells that either did or did not have PTRF.

The results of the study showed that when there was an absence of PTRF, the cells were unable to make sufficient new protein that responds adequately to cycles of fasting and refeeding (equivalent to the human dietary cycle). Additional studies have described how PTRF works at the molecular level, as well as the inefficiency of this process in most obesity cases, which may be linked between the similar deleterious consequences of too little and too much fat, according to the study.

The findings may eventually lead to new opportunities for diabetes treatment, but authors caution that type 2 diabetes is still a complex condition, and proteins other than PTRF can also be a contributing factor to the development of the disease.

“(Even as more research unfolds) diet and exercise continue to be the first choice for preventing and treating type 2 diabetes,” said lead study author Libin Liu, PhD and researcher Paul Pilch, PhD.