New Study Explains Link Between High Fat Diet and Diabetes

Millions of people around the world suffer from type 2 diabetes, but scientists still do not fully understand what causes this widespread and complex disease.  One unresolved question that has divided researchers is how big of a role mitochondria play in the onset of the disease. Mitochondria are the powerhouse of almost all living cells; these tiny organelles make the energy that a cell needs to survive and function. Now, a new study from the Department of Human Health and Nutritional Sciences has shown that a high-fat diet can induce dysfunction in mitochondria, increasing susceptibility to diabetes.

“It is not new that studies are being conducted to study the role of mitochondria as the cause of diabetes,’’ says Prof. Graham Holloway, who led the study. “But in contrast to previous studies, we decided to study mitochondria by mimicking real-life conditions as close as possible.”

Previous studies that investigated how a high-fat diet influences diabetes may have overlooked the role of mitochondria because they did not accurately reflect the normal concentration of compounds used to produce energy in a cell. 

Holloway and PhD student Paula Miotto took a different approach and fed mice either a normal or high-fat diet for four weeks. At the end of the study, mice fed with a high fat diet had increased body weight and fat stores, and more fat breakdown in their muscles compared to mice that consumed a normal diet.  Most revealing of all, the mitochondrial function of high-fat diet mice was also significantly reduced.

“The results were exactly what we were expecting,’’ says Holloway.

The connection between mitochondrial function and diabetes lies in blood glucose.  After a meal, the level of glucose in the blood rises.  So does the amount of insulin, which is the signal that commands muscles to take the glucose from the bloodstream and utilize it for energy. Mitochondria play an essential role in this process by regulating the intake of glucose into muscle cell.

But when a mouse is fed a high fat diet, it causes changes in the mitochondria, which in turn, disrupt the ability of skeletal muscle to respond to insulin. As muscle cells become less responsive to insulin they take up less glucose, leading to high blood sugar.

“As a result of this study we were able to come up with a possible mechanism by which a high fat diet increases vulnerability to insulin resistant diabetes,” says Holloway.

Understanding the precise mechanisms that cause diabetes is important to identifying novel drugs to treat the condition, and Holloway recommends additional studies to further zero in on the precise role of mitochondria in diabetes.

In the meantime, for anyone looking to reduce their risk of diabetes, Holloway has a ready solution.

‘’Mitochondria respond very robustly to diet and exercise,” he notes.  “Because we have established that mitochondrial function is linked to diabetes, we should now be advocating for nutritional diets and life style modifications like exercise that can change mitochondria to influence the susceptibility to diabetes.’’ 

Funding was provided by the Natural Sciences and Engineering Research Council of Canada, the Canadian Foundation for Innovation and the Ontario Research Fund.

Read the full study in the journal Diabetes.

Read about other CBS Research Highlights.