Effect of HIF2α knockdown in the neurons of mediobasal hypothalamus on body weight and energy metabolism in mice
Dilihumaier Duolikun1 Aizimaiti Rouzijiang1 MA Lijuan1 GUO Hai2 YAO Qiaoling1
1.Room 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
Abstract：Objective To investigate the effects of hypoxia-inducible factor 2α (HIF2α) knockdown in the neurons of the mediobasal hypothalamus on body weight, food intake and energy metabolism in mice. Methods Sixteen HIF2αflox/flox transgenic male mice were selected and they were divided into control group injected with AAV-hSyn-GFP virus at the mediobasal of the hypothalamus (n=8) and HIF2α knockdown group injected with AAV-hSyn-cre-GFP virus groups of mice were fed with normal chow and their body weight and food intake were weighed every three days. After four weeks, the body composition and energy metabolic rate of mice were measured by nuclear magnetic resonance analyzer and metabolic cage. Results The body weight of mice in the control group on days 18 to 30 was higher than that on days 3, the difference was statistically significant (P＜0.05). The body weight of mice in HIF2α knockout group on days 9 to 30 was higher than that on days 3, the difference was statistically significant (P＜0.05); the body weight of mice in HIF2α knockdown group was higher than that in control group on the 15th to 30th day, and the difference was statistically significant (P＜0.05). The food intake of mice in the control group on the 12th to 30th day was significantly different from that on the 3rd day (P＜0.05). The food intake of mice in HIF2α knockout group on days 9 to 30 was higher than that on days 3, and the difference was statistically significant (P＜0.05). The food intake of mice in HIF2α knock-down group was higher than that in control group from 9 to 30 days, and the difference was statistically significant (P＜0.05). Body fat weight, body fluid weight and lean body mass in HIF2α knockout group were higher than those in control group (P＜0.01). The oxygen consumption (VO2) during the day and night in the knockdown group was lower than that in the control group (P＜0.05 or P < 0.01); in control group, VO2 at night was higher than that at day (P＜0.05). There was no significant difference in VO2 between HIF2α knockdown group at night and daytime (P＞0.05). The carbon dioxide production (VCO2) in the HIF2α knockdown group at night was lower than that in the control group (P＜0.05), and there was no statistical significance in the daytime VCO2 between the two groups (P＞0.05). In control group, VCO2 at night was higher than that at day (P＜0.05). There was no significant difference in VCO2 between night and day in HIF2α knockdown group (P＞0.05). The daytime respiratory entropy (RER) in HIF2α knockdown group was higher than that in control group (P＜0.05). There was no significant difference between night and day RER between the two groups (P＞ 0.05). The energy expenditure (EE) in HIF2α knockdown group was lower than that in control group during the day and night (P＜0.05 or P＜0.01). In the control group, EE at night was higher than that at day, and the difference was statistically significant (P＜0.05). There was no significant difference in EE between HIF2α knockdown group at night and daytime (P＞0.05). The night activity of HIF2α knockdown group was lower than that of control group (P＜0.05), but there was no significant difference between the two groups in daytime activity (P＞0.05). The activity level of the control group at night was higher than that at day (P＜0.05). There was no significant difference in activity level between HIF2α knockdown group at night and daytime (P＞0.05). The food intake of HIF2α knockdown group during the day was higher than that of control group (P＜0.05), and there was no statistical significance in food intake at night between the two groups (P＞0.05). The food intake in the control group was higher at night than at day (P＜0.01). There was no significant difference in food intake between HIF2α knockdown group at night and day (P＞0.05). Conclusion Under normal chow-diet feeding, knockdown of HIF2α in the mediobasal hypothalamus may lead to an increase in body weight in mice. The underlying mechanisms may involve increased food intake, decreased energy expenditure, and disordered circadian rhythms.
迪丽胡买尔·多力坤1 艾孜买提·肉孜江1 马丽娟1 郭海2 姚巧玲1. 下丘脑内侧基底部神经元HIF2α敲低对小鼠体重和能量代谢率的影响[J]. 中国医药导报, 2023, 20(20): 10-16,22.
Dilihumaier Duolikun1 Aizimaiti Rouzijiang1 MA Lijuan1 GUO Hai2 YAO Qiaoling1. Effect of HIF2α knockdown in the neurons of mediobasal hypothalamus on body weight and energy metabolism in mice. 中国医药导报, 2023, 20(20): 10-16,22.
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