Neuronal HIF-1α expression in mediobasal hypothalamus affects glycolipid metabolism and body weight in mice fed with high-fat diet.

Abstract

This study aimed to explore the interaction between the expression of neuronal HIF-1α in the mediobasal hypothalamus and food intake, glycolipid metabolism and body weight (BW) in mice consuming high-fat diet (HFD). In HIF-1α^flox/flox mice, AAV-hSyn-GFP (NC group) or AAV-hSyn-cre-GFP (KD group) virus was injected into medial base of the hypothalamus. Frozen brain tissue sections confirmed the presence of the virus within the hypothalamus of mice after 28 days of AAV injection, including reporter signals within the arcuate nucleus, dorsomedial hypothalamic nucleus (DMH) and ventromedial hypothalamus (VMH). Consistently, the levels of HIF-1α mRNA in the ventral hypothalamus were significantly lower in the KD group compared to the NC group. These KD mice also demonstrated significantly increased food intake, body weight (BW), total cholesterol (TC), high-density lipoprotein (HDL), low-density lipoprotein (LDL) and serum insulin, combined with higher blood glucose, compared to NC animals. However, the levels of triglycerides and FFA were similar in both groups. Significant differences in p-Akt levels were not observed in the skeletal muscle, liver or epididymal fat in KD mice after insulin injection. In conclusion, the knockdown of HIF-1α within the neurons of mediobasal hypothalamus results in an increase in the appetite of mice fed with HFD, which in turn leads to a significant dysregulation of lipid and glucose metabolism and a corresponding increase in weight. Therefore, the neuronal HIF-1α expression in the mediobasal hypothalamus may be a critical regulator of glycolipid metabolism and body weight control when a high-fat diet is consumed.