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SPLTRAK Abstract Submission
Intermittent fasting reduces pancreatic fat and prevents type 2 diabetes in mice
MANDY STADION1,2, CHARLINE QUICLET1,2, ANNEKE GÄSSLER1,2, CHRISTIAN BAUMEIER1,2, TIM J. SCHULZ3,2, ANNETTE SCHÜRMANN1,2
1German Institute for Human Nutrition Potsdam-Rehbruecke, Department of Experimental Diabetology, Potsdam, Germany/2German Center for Diabetes Research (DZD), München-Neuherberg, Germany/3German Institute for Human Nutrition Potsdam-Rehbruecke, Department of Adipocyte Development and Nutrition, Potsdam, Germany
   Obesity is accompanied by ectopic fat deposition in peripheral tissues including liver, muscle, and pancreas, but the impact of pancreas fat on islet cell biology and type 2 diabetes (T2D) risk is still poorly understood. Intermittent fasting (IF) is known to improve glucose homeostasis and insulin sensitivity in mice and humans. Under a high-fat diet, male New Zealand Obese (NZO) mice develop obesity as well as T2D, whereas obese B6.V-ob/ob (ob/ob) mice are diabetes-resistant. We aim to investigate whether IF affects pancreatic fat cell accumulation in diabetes-prone NZO mice and whether pancreatic adipocytes directly influence islet cell function. We fed NZO mice either a high-fat diet ad libitum or fasted them every other day and ectopic fat accumulation, glucose homoeostasis, insulin sensitivity, and islet function was analyzed and compared to results obtained from ad libitum-fed ob/ob mice. To study the direct effect of pancreatic adipocytes on islet glucose-stimulated insulin secretion, co-culture experiments were performed. Diabetes-resistant ob/ob mice displayed higher liver fat (~4-fold) but lower pancreatic fat (-46%) as compared with diabetes-prone NZO mice. IF in NZO mice resulted in lower pancreatic fat (-32%) as well as in improved glucose tolerance, insulin sensitivity, and islet function. Co-culture experiments demonstrated that pancreatic adipocytes induce insulin hypersecretion in mouse islets. Our data indicate that pancreatic adipocytes participate in the development of islet dysfunction and T2D in NZO mice and that IF represents an efficient strategy to decrease pancreatic fat deposition and T2D risk.

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