Overexpression of SIRT6 could prevent progression of diabetes, study finds

Targeting obesity through exercise and caloric restriction is often the first approach to treating diabetes and related cardiovascular disorders, such as cardiomyopathy. A recent study on animals published in The FASEB newspaper have explored an alternative treatment based on sirtuin to block the development of obesity and cardiomyopathy under conditions of excessive nutrition, when the restriction of diet and physical exercise are not feasible.

For this study, the researchers evaluated the potential of SIRT6 – often considered a longevity factor – to protect the heart against the development of diabetic cardiomyopathy. Previous research has shown that a SIRT6 nuclear sirtuin deficiency can lead to the development of cardiomyopathy in mice.

To conduct the experiment, the researchers generated a group of transgenic mice overexpressing SIRT6 for the whole body (Tg.SIRT6). The research team then observed the following groups of mice for 24 weeks: 1) non-transgenic control mice (N.Tg) fed a normal diet; 2) Tg.SIRT6 mice fed a normal diet; 3) non-transgenic control mice (N.Tg) fed a diet high in fat and sucrose (HF-HS); and 4) Tg.SIRT6 mice receiving an HF-HS diet.

As expected, N.Tg control mice fed a HF-HS diet developed obesity, compared to N.Tg and Tg.SIRT6 mice fed a normal diet. Surprisingly, however, Tg.SIRT6 mice fed an HF-HS diet did not develop obesity. This unexpected finding has shown that overexpression of SIRT6 can prevent the development of obesity under conditions of excessive nutrition.

"We believe that the information presented in this study will help us understand the pathogenesis of diabetic cardiomyopathy and its progression," said Mahesh P. Gupta, MS, Ph.D., professor and director of the Cardiothoracic Surgery Research Program of the University of Chicago. "One day, a SIRT6-based treatment would be beneficial for patients unable to exercise or make dietary restrictions on a regular basis to prevent the progression of diabetes."

"These are intriguing results," said Thoru Pederson, Ph.D., editor-in-chief of The FASEB newspaper. "We have always thought that sirtuin pathways influence" aging "generically, but there are of course specific elements and this study has uncovered a mechanism that interacts with the morbidity / mortality factors of the disease. 39, obesity and diabetes, siruine syndrome. "