Change of ghrelin-ghsr pathway in 4-week intermittent hypoxic exposure improving obesity in mice / 中国组织工程研究

ABSTRACT

BACKGROUND: Weight loss under hypoxic exposure is related to a reduction in food intake. Decreased gastric Ghrelin levels can reduce food intake, but whether digestive nutritional absorption disorders and dyslipidemia caused by obesity can be regulated through Ghrelin-growth hormone secretagogue receptor (GHSR) pathway under intermittent hypoxia is unclear yet. OBJECTIVE: To explore the effect of intermittent hypoxia exposure on Ghrelin-GHSR pathway in gastric tissues of obese mice. METHODS: Thirty C57BL/6J male mice were randomly divided into a control group (n=8) and a high fat diet group (n=22, fed with high fat diet). After 8 weeks high fat diet, obesity models were successfully established in 16 mice with high fat diet, and then were randomly divided into an obese control group (n=8) and an obese hypoxic group (n=8, 11.2% oxygen concentration, 8 hours per day, 6 times per week). The mice whose remaining body mass did not exceed the average body weight of the normal control group by 20% were discarded. After intervention, the serum biochemical indicators and Ghrelin level were tested; the Ghrelin and GHSR-1a mRNA expressions were tested by RT-PCR; gastric tissue morphology was observed by hematoxylin-eosin staining; the mean absorbance values of Ghrelin and Ghrelin O-acyltransferase (Goat) were measured by immunohistochemistry; the protein expressions of hypothalamic growth hormone secretagogue hormone receptor 1a (GHSR-1a), Ghrelin and Goat were detected by western blot. The study protocol was approved by the Sports Science Ethics Committee of Beijing Sport University, approval No. 2015021. RESULTS AND CONCLUSION: (1) The body mass of the obese control group was significantly higher than that of the control group and obese hypoxic group after 4-week hypoxic intervention. (2) The blood glucose, total cholesterol, and triacylglycerol levels were obviously higher in the obese control group than the control group. Compared with the obese control group, the blood glucose and total cholesterol levels were significantly lower in the obese hypoxic group, while the serum Ghrelin level was significantly higher in the obese hypoxic group. (3) The Ghrelin mRNA relative expression in gastric tissue of the obese control group was evidently lower than that of the obese hypoxic group, and the GHSR-1a mRNA expression in the hypothalamus was significantly lower in the obese control group than the control group. (4) The obese hypoxic group had a regular, dense and uniform distribution of gastric fundus gland main cells. (5) The mean absorbance values of Ghrelin and Goat as well as the protein contents of GHSR-1a, Ghrelin and Goat in the obese hypoxic group were evidently higher than those in the obese control group. These results indicate that 4-week hypoxic exposure can significantly increase the expression of Ghrelin and Goat in gastric tissue and GHSR-1a in the hypothalamus, decrease blood glucose level and body mass, and improve the adverse effects of obesity in obese mice.