New Insights on Neuronal Functions of Ghrelin Receptor GHS-R in Obesity

Obesity is defined as excessive fat accumulation caused by the imbalance of energy intake versus expenditure. Low-grade chronic inflammation is a hallmark of obesity, and it is closely linked to insulin resistance. Obesity-induced inflammation and its associated metabolic dysfunctions underlay pathological processes of many chronic diseases such as insulin resistance, diabetes, sarcopenia and cardiovascular disease. Ghrelin is the only known circulating orexigenic hormone; it stimulates growth hormone release, and increases adiposity and insulin resistance. Ghrelin’s functions are mediated through its receptor, growth hormone secretagogue receptor (GHS-R). The brain plays a critical role in energy homeostasis and energy metabolism. GHS-R is primarily expressed in the brain; the brain is a key ghrelin targeting site. The current review discusses the insights we have gained from global GHS-R knockout mice and neural conditional GHS-R knockout mice, specifically involving the roles of GHS-R in food intake, feeding adaptation, thermogenesis, meta-inflammation, and physical activity.