The role of intermittent fasting and pancreatic adipocytes on type 2 diabetes in NZO mice

Einleitung:

Obesity results in a dysfunctional adipose tissue followed by an ectopic fat storage. Under a high-fat diet (HFD), New Zealand Obese (NZO) mice develop obesity and type 2 diabetes (T2D). We have shown that intermittent fasting (IF) prevents the onset of T2D in NZO mice. The actual aim was to investigate whether IF prevents pancreatic fat accumulation and how pancreatic adipocytes directly affect islet function.

Methoden:

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

Ergebnisse:

IF resulted in decreased hepatic (-35%) and pancreatic fat (-32%) accompanied by improved glucose tolerance, insulin sensitivity and islet function. Co-culture of pancreatic adipocytes with islets induced a hypersecretion of insulin. Pancreatic adipocytes secreted higher NEFA levels than adipocytes derived from inguinal white adipose tissue.

Schlussfolgerung:

Our data indicate that pancreatic adipocytes participate in the development of islet dysfunction and T2D in NZO mice. IF displays an efficient strategy to improve glucose metabolism in diabetes-prone mice, in part, by limiting the lipid accumulation in the pancreas.