Time-restricted feeding restored insulin-growth hormone balance and improved substrate and energy metabolism in MC4RKO obese mice

Abstract

Abstract Background Dysregulation of metabolic regulatory hormones often occurs during the progress of obesity. Key regulatory hormone Insulin-GH balance has recently been proposed to maintain metabolism profiles. Time-restricted feeding (TRF) is an effective strategy against obesity without detailed research on pulsatile GH releasing patterns. Methods TRF was performed in an over-eating MC4RKO obese mouse model using normal food. Body weight and food intake were measured. Series of blood samples were collected for 6 h pulsatile GH profile, glucose tolerance test and insulin tolerance test at 5, 8, and 9 weeks of TRF, respectively. Indirect calorimetric recordings were performed by Phenomaster system at 6 weeks for 1 week and body composition was measured by Nuclear magnetic resonance spectroscopy (NMR). Substrate and energy metabolism related gene expression were measured in terminal liver and subcutaneous white adipose tissues. Results TRF increased pulsatile GH secretion in dark phase and suppressed hyperinsulinemia in MC4RKO obese mice to reach a reduced insulin/GH ratio. This was accompanied by the improvement in insulin sensitivity, metabolic flexibility, glucose tolerance and decreased glucose fluctuation, together with appropriate modification of gene expression involved in substrate metabolism and adipose tissue browning. NMR measurement showed that TRF decreased fat mass but increased lean mass. Indirect calorimeter recording indicated that TRF decreased the respiratory exchange ratio (RER) reflecting consumption of more fatty acid in energy production in light phase and increased the oxygen consumption during activities in dark phase. Conclusions TRF effectively decreases hyperinsulinemia and restores pulsatile GH secretion in the overeating obese mice with significant improvement in substrate and energy metabolism and body composition without reducing total caloric intake.