Effects of HIF1α deficiency in the neurons of mediobasal hypothalamus on body weight and glucose metabolism in mice
Aizimaiti·Rouzijiang1* SHAN Weibi2* GUO Hai3 YAO Qiaoling1
1.Department of Physiology, School of Basic Medical Sciences, Xinjiang Medical University, Xinjiang Uygur Autonomous Region, Urumqi 830011, China; 2.Department of Anesthesiology, the First Affiliated Hospital of Xinjiang Medical University, Xinjiang Uygur Autonomous Region, Urumqi 830011, China; 3.Department of Dermatology, the First Affiliated Hospital of Xinjiang Medical University, Xinjiang Uygur Autonomous Region, Urumqi 830011, China
Abstract Objective To investigate the effects of hypoxia inducible factor 1α (HIF1α) deficiency in the neurons of mediobasal hypothalamus (MBH) on body weight and blood glucose metabolism in mice. Methods Thirty HIF1αflox/flox male mice were sdected, two mice with similar body weight were randomly divided into experimental group and control group, each group of 15 mice only. The average body weight difference between the two groups was no more than 2 g. Mice in the experimental group were injected with cre adeno-associated virus AAV-hSyn-cre-GFP to selectively knock down HIF1α in MBH neurons; mice in the control group were injected with AAV-hSyn-GFP. The injection site in both groups was the neurons of MBH (bregma-1.5, midline±0.5 [both sides], dorsoventral 5.8 [skull surface]). Each side was injected with 0.5 μL of virus at a concentration of 1.45E+13 v.g./mL. The body weight and food intake of the mice were weighed every day after injection, and the serum glucose and insulin contents of the mice were detected four weeks later. Results Overall analysis of the body weight of mice showed that there were statistically significant differences between groups, time point comparison and interaction (P ＜ 0.05). Comparison within groups: the body weight of mice in both groups on the 15th, 25th and 28th day was all higher than that on the 5th day, with statistical significance (all P ＜ 0.05). Comparison between groups: the body weight of the experimental group on the 15th, 25th and 28th day was higher than that of the control group, with statistical significance (all P ＜ 0.05). Overall analysis of the food intake of mice showed that there were statistically significant differences between groups, time point comparison and interaction (P ＜ 0.05). Comparison within groups: there was no significant difference in food intake between the control group on the 15th, 25th and 28th day and the 5th day (P > 0.05), but the food intake of the experimental group on the 15th, 25th and 28th day was all higher than that on the 5th day, with statistical significance (all P ＜ 0.05). Comparison between groups: the food intake of the experimental group on the 15th, 25th and 28th day was higher than that of the control group, with statistical significance (all P ＜ 0.05). There was no significant difference in fasting blood glucose levels between the two groups (P > 0.05). Compared with the control group, the serum insulin content of the experimental group was increased, and the difference was statistically significant (P < 0.05). Correlation analysis showed that there was a positive correlation between serum insulin content and body weight (r = 0.660, P ＜ 0.05). Conclusion The hypothalamic neuron HIF1α plays an important role in the regulation of body weight balance in mice under normal oxygen. Hypothalamic HIF1α deficiency can cause weight gain, increased appetite, abnormal glucose metabolism and insulin resistance in mice.
Aizimaiti·Rouzijiang1* SHAN Weibi2* GUO Hai3 YAO Qiaoling1. Effects of HIF1α deficiency in the neurons of mediobasal hypothalamus on body weight and glucose metabolism in mice[J]. 中国医药导报, 2021, 18(15): 13-16.
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