1861-P: Short-Term Overfeeding with Dairy Fat Impairs Insulin Sensitivity in Muscle and Liver but Increases Adipose Tissue Insulin Sensitivity and Suppresses Postprandial Glucose Rise in Healthy Nonobese Men

Previous studies have demonstrated that saturated fat intake increases the risk of type 2 diabetes (T2DM) due to reduction of insulin sensitivity. On the other hand, the consumption of dairy fat that predominantly includes saturated fat is reported to be protective against T2DM. However, its underlying mechanism has not been fully understood. To address this, we recruited 21 healthy non-obese men and evaluated metabolic changes before and after 6-day high-calorie, high-fat diet (HCHFD) consisting of a regular diet plus 45% energy excess by supplementation with dairy fat. We measured intrahepatic lipid (IHL) and intramyocellular lipid (IMCL) in tibialis anterior muscle by 1H-MRS and metabolic rate during sleeping by metabolic chamber. One day after the measurement, we performed meal test, and the next day, we measured tissue specific insulin sensitivity by 2-step hyperinsulinemic euglycemic clamp. After the HCHFD, body weight was increased by 0.4 kg, and IMCL and IHL were also increased by 47% and 200%, respectively. On the other hand, hepatic and muscle insulin sensitivity showed only a modest decrease by 8% and 4%, respectively. Consistently, fasting endogenous glucose production elevated by only 3% without altering insulin level; however, unexpectedly, fasting free fatty acid (FFA) greatly decreased by 43%, suggesting increased adipose tissue insulin sensitivity (ATIS), and total ketone body levels was decreased by 53% and glucose oxidation during sleeping was consistently increased. Further, post-prandial glucose rise during the meal test was suppressed after the HCHFD, although insulin secretion was lower during the test. In conclusion, short-term HCHFD by dairy fat supplementation increased ATIS and glucose oxidation, and suppressed post-prandial glucose rise with lowered insulin secretion. These metabolic changes by dairy fat may be beneficial to prevent T2DM. Disclosure D. Sugimoto: None. Y. Tamura: Advisory Panel; Self; Astellas Pharma Inc. Research Support; Self; Kowa Company, Ltd. Speaker’s Bureau; Self; Novo Nordisk Inc., Ono Pharmaceutical Co., Ltd. S. Kadowaki: None. Y. Someya: None. H. Kaga: None. R. Suzuki: None. S. Kakehi: None. N. Yamasaki: None. M. Sato: None. A. Kanazawa: Speaker’s Bureau; Self; Novartis Pharma K.K., Sanofi, Takeda Pharmaceutical Company Limited. R. Kawamori: None. H. Watada: Advisory Panel; Self; Abbott, Ajinomoto, Astellas Pharma Inc., Boehringer Ingelheim Pharmaceuticals, Inc., Fuji Film, Janssen Pharmaceuticals, Inc., Kowa Company, Ltd., Kyowa Hakko Kirin Co., Ltd., Mitsubishi Tanabe Pharma Corporation, Novo Nordisk Inc., Ono Pharmaceutical Co., Ltd., Sanofi-Aventis, Takeda Pharmaceutical Company Limited, Terumo Medical Corporation. Research Support; Self; Astellas Pharma Inc., Bayer Yakuhin, Ltd., Boehringer Ingelheim Pharmaceuticals, Inc., Daiichi Sankyo, Eli Lilly Japan K.K., Kissei Pharmaceutical Co., Ltd., Kowa Company, Ltd., Kyowa Hakko Kirin Co., Ltd., Merck Sharp & Dohme Corp., Mitsubishi Tanabe Pharma Corporation, Novartis Pharma K.K., Novo Nordisk Inc., Ono Pharmaceutical Co., Ltd., Otsuka Pharmaceutical Co., Ltd., Pfizer Japan Inc., Sanofi-Aventis, Sanwa Kagaku Kenkyusho, Shionogi & Co., Ltd., Sumitomo Dainippon Pharma Co., Ltd., Sumitomo Dainippon Pharma Co., Ltd., Taisho Pharmaceutical Co., Ltd., Takeda Pharmaceutical Company Limited, Teijin Pharma Limited, Yakult. Speaker’s Bureau; Self; Astellas Pharma Inc., AstraZeneca, Bayer Yakuhin, Ltd., Boehringer Ingelheim Pharmaceuticals, Inc., Daiichi Sankyo, Eli Lilly Japan K.K., Kissei Pharmaceutical Co., Ltd., Kowa Company, Ltd., Kyowa Hakko Kirin Co., Ltd., Merck Sharp & Dohme Corp., Mitsubishi Tanabe Pharma Corporation, Novartis Pharmaceuticals Corporation, Novo Nordisk Inc., Ono Pharmaceutical Co., Ltd., Sanofi-Aventis, Sanwa Kagaku Kenkyusho, Sumitomo Dainippon Pharma Co., Ltd., Takeda Pharmaceutical Company Limited. Funding Ministry of Education, Culture, Sports, Science and Technology of Japan (18H03196)