Endocrine Abstracts

Introduction: Anorexia, one of the major problems at high altitude caused by alterations in adipose, gut and pancreatic hormones responsible for appetite regulation and energy balance may be alleviated by understanding the changes during hypoxia. The present study was aimed to elucidate the response of peripheral tissues to hypobaric hypoxic exposure in terms of circulating levels and expression pattern of appetite regulatory hormones, adipose cell morphology and glucose regulation.

Methodology: Male Sprague–Dawley rats were exposed to hypobaric hypoxia at a simulated altitude of 7620 m in a hypobaric chamber for different duration up to 7 days.

Results: Hypoxia exposure caused reduction in food intake and body weight. Plasma leptin levels initially increased and decreased to normal at 24 h of hypoxia. Circulating levels of ghrelin, resistin, insulin and glucose increased while CCK, GLP1 and PPY decreased during hypoxia. Decrease in adipocyte size was observed during hypoxia. Increased resistin, GRP78 expression and decreased leptin, IL6, Caspase12, PGC1β expression in adipose tissue was observed during hypoxia. Adiponectin mRNA decreased in adipose tissue while there was no change in protein levels. Stomach ghrelin and ghrelin receptor expression increased while CCKAR, PPARα and PPARδ expression decreased during hypoxia. Liver CCKAR, PPARδ and Caspase12 decreased while GRP78, PPARα and PGC1α increased during hypoxia.

Discussion and conclusion: Increase in both glucose and insulin levels indicate insulin resistance. Increased GRP78 shows onset of endoplasmic reticulum (ER) stress in adipose tissue. Decreased PGC1β shows halt of adipogenesis and weight loss is due to reduction in adipose cell size. In conclusion hypoxia impairs peripheral tissues response by altering expression of appetite regulatory hormones, reducing adipocyte size, impairment in glucose clearance and inducing ER stress which altogether might be a few causative factors for anorexia.