Intermittent fasting reduces fat infiltration in the pancreas and prevents diabetes in NZO mice fed a high-fat diet

Background:

In obesity, a dysfunction of adipose tissue results in ectopic fat deposition in non-adipose tissue organs such as liver, muscle but also pancreas. Following a caloric-enriched diet, New Zealand Obese (NZO) mice develop obesity and type 2 diabetes due to a β-cell loss while B6.V-ob/ob (ob/ob) obese mice are diabetes-resistant because of a massive β-cell proliferation. Intermittent fasting (IF) has been shown to have positive effects on diabetes susceptibility in human and animal, due to an improved liver metabolism in NZO mice. However, the effects of IF on fat infiltration in the pancreas, β-cell function and glucose homeostasis remain unknown.

Methods:

NZO mice under high-fat diet from weaning to 9 weeks of age were fasted every other day (IF) and compared to ad libitum fed control NZO (AL) and ob/ob mice.

Results:

IF animals gained less weight, had a higher lean mass (+5 and +38%, respectively) and lower fat mass (-9.5 and -57%, respectively) and blood glucose levels compared to AL and ob/ob animals. They also displayed a better glucose tolerance compared to AL animals and higher insulin sensitivity in comparison to AL and ob/ob mice. Moreover, pancreatic adipocytes were smaller and in a lower number in IF animals, and pancreas and liver triglycerides concentrations were significantly reduced in animals from IF group compared to AL and ob/ob groups.

Conclusion:

IF effectively protects NZO diabetes-susceptible mice from diabetes via a reduction of fat cell infiltration in the pancreas and fat accumulation in the liver and improves their glucose metabolism.