Inhibitory Effects of Intranasal Insulin Administration on Fat Oxidation during Exercise Are Diminished in Overweight Young Individuals
Authors: YOKOYAMA HISAYO , TAKEDA RYOSUKE , KAWAI ERIKO , OTA AKEMI , MORITA EMIKO , IMAI DAIKI , SUZUKI YUTA , MORIOKA TOMOAKI , EMOTO MASANORI , INABA MASAAKI , OKAZAKI KAZUNOBU 
Published: June 2018

Endurance training at a level (FATmax) that raises the maximal fat oxidation rate (max FOR) may contribute to body weight loss in obese individuals. However, max FOR and FATmax are reduced in subjects with obesity and/or with insulin resistance compared with those without. On the other hand, in humans, intranasal insulin administration increases the concentration of insulin in cerebrospinal fluid when peripheral effects are absent, resulting in reduced food intake and body weight. However, it remains unclear whether insulin delivery to the brain affects fat oxidation during exercise. In this study, we examined the effects of nasal insulin administration on max FOR during exercise in 11 normal-weight (N group) and seven overweight (O group) young individuals. On two separate days, either 40 IU regular insulin (INS) or normal saline, as placebo (PL), was randomly administered intranasally after overnight fasting, and then each participant underwent a graded exercise test. Indirect calorimetry was used to assess max FOR during exercise and FATmax. Blood insulin and glucose levels did not change after insulin administration. In the N group, max FOR tended to decrease in the INS trial (p = 0.050); FATmax and the total amount of fat oxidation during exercise were significantly smaller in the INS trial than in the PL trial. Max FOR was significantly smaller in the O group than in the N group (p = 0.021) and was not influenced by insulin administration. Blood adrenaline levels increased by exercise tended to be reduced by insulin administration in the N group only.
In conclusion, intranasal insulin administration reduces fat oxidation during exercise without increasing peripheral insulin levels, possibly via the suppression of sympathetic nerve activity. The inhibitory effects of intranasal insulin administration on fat oxidation during exercise are diminished in overweight subjects, suggesting cerebral insulin effects are attenuated in this population.

Disclosure
H. Yokoyama: None. R. Takeda: None. E. Kawai: None. A. Ota: None. E. Morita: None. D. Imai: None. Y. Suzuki: None. T. Morioka: Consultant; Self; Ono Pharmaceutical Co., Ltd.. Research Support; Self; Novartis Pharma K.K., MSD K.K., Eli Lilly and Company, Sanofi K.K., Mitsubishi Tanabe Pharma Corporation. Speaker's Bureau; Self; Takeda Pharmaceuticals U.S.A., Inc., Novo Nordisk Inc., Kowa Pharmaceuticals America, Inc., Astellas Pharma US, Inc., Boehringer Ingelheim Pharmaceuticals, Inc., Sumitomo Dainippon Pharma Co., Ltd. M. Emoto: Speaker's Bureau; Self; Eli Lilly and Company, Boehringer Ingelheim Pharmaceuticals, Inc., Sumitomo Dainippon Pharma Co., Ltd.. Research Support; Self; Astellas Pharma Inc, Ono Pharmaceutical Co., Ltd., Kissei Pharmaceutical Co., Ltd., Kowa Pharmaceutical Company Ltd., Taisho Toyama Pharmaceutical Co., Ltd., Mitsubishi Tanabe Pharma Corporation. M. Inaba: None. K. Okazaki: None.