Vasopressin V1a receptor and metabolism in humans and mice

 

Shizue Masuki and Hiroshi Nose

Department of Sports Medical Sciences, Shinshu University Graduate School of Medicine, Matsumoto, Japan

 

To assess the role of vasopressin V1a receptor in glucose and lipid metabolisms, we continuously measured oxygen consumption rate (VO₂, mass spectrometry), carbohydrate production rate (VCO₂) and activity during the day (inactive phase) and night (active phase) in mice genetically deficient of vasopressin V1a receptor (KO). Activity, VO₂, and VCO₂ were higher at night than during the day (P<0.05) with no differences between wild type (WT) and KO (P>0.1). Respiratory quotient (RQ) also increased at night compared with during the day (P<0.05) in both groups. However, we found that RQ tended to be lower in KO than WT during the day (0.83±0.02 vs 0.87±0.01, P=0.1), and it was more prominent at night (0.87±0.02 vs 0.96±0.01, P<0.01), suggesting that catabolic rate of glucose was lower while that of lipid was higher in KO than WT, more markedly at night. These results suggest that V1a receptor modulates glucose and lipid metabolisms during active phase more than inactive phase.

Based on the results in mice, we assessed whether single nucleotide polymorphism rs1042615 in vasopressin V1a receptor altered the indices of life-style associated diseases in middle-aged and older humans (67±7 (SD) yr) and, if so, whether it also altered the effects of high-intensity interval walking training (IWT) on them. CC, CT, and TT carriers of rs1042615 (42, 118, and 64 men, respectively) performed IWT; 5 sets of 3-min fast walking at ³70% peak aerobic capacity (VO_2peak) and 3-min slow walking at 40% VO_2peak/day, ³4 days/wk, for 5 mos. Before IWT, body mass index (BMI) and diastolic blood pressure (DBP) were 25.1±0.3 kg/m² and 84±1 mmHg in TT, higher than 23.6±0.4 kg/m² and 78±1 mmHg in CC, respectively, (P<0.01), whereas the differences disappeared after IWT despite similar training achievement between the groups (P>0.6). After IWT, BMI and DBP decreased in TT (-0.9±0.1 kg/m² and -5±1 mmHg, respectively), more than in CC (-0.5±0.1 kg/m² and 1±1 mmHg, respectively; P<0.05), with a greater decrease in blood LDL cholesterol in TT than CC (P<0.01). Together, these results suggest that the polymorphism rs1042615 in V1a receptor altered the indices of life-style associated diseases in middle-aged and older men and the effects of IWT by modulating glucose and lipid metabolisms.

 

Key words: metabolism, aging, genetics, exercise, blood pressure