Intermittent fasting prevents fatty pancreas and type 2 diabetes in NZO mice

Background:

Obesity is associated with a dysfunctional adipose tissue and ectopic fat deposition in liver, muscle and pancreas. Under a high-fat diet (HFD), New Zealand Obese (NZO) mice develop obesity as well as type 2 diabetes (T2D), whereas obese B6.V-ob/ob (ob/ob) mice are diabetes-resistant. Intermittent fasting (IF) has been shown to lower T2D risk in mice and humans. The aim of the study was to investigate whether IF prevents pancreatic fat cell infiltration and whether pancreatic adipocytes directly affect islet function.

Methods:

NZO mice were fed a HFD ad libitum (AL) or fasted every other day (intermittent fasting, IF) and ectopic fat accumulation, glucose homoeostasis, insulin sensitivity and islet function were analyzed and compared to ad libitum-fed ob/ob mice. To determine the impact of pancreatic adipocytes on glucose-stimulated insulin secretion co-culture experiments were performed.

Results:

Ob/ob mice exhibited lower pancreatic fat (µg triglycerides/µg protein, ob/ob: 1.71 ± 0.24; NZO-AL: 3.15 ± 0.38) and higher total pancreatic insulin levels compared to NZO mice. IF in NZO mice resulted in lower fat accumulation in the pancreas (-32%) and improved glucose tolerance, insulin sensitivity and islet function. Co-culture experiments revealed that pancreatic adipocytes induce hypersecretion of insulin in mouse islets.

Conclusion:

Our data indicate that pancreatic adipocytes participate in the development of islet dysfunction and T2D in NZO mice. Intermittent fasting is an efficient strategy to improve glucose metabolism in diabetes-prone mice by limiting the infiltration of adipocyte in the pancreas.