Potential Role of TRPV4 in Stretch-Induced Ghrelin Secretion and Obesity

Abstract

Obesity is an important health problem, which can be prevented through appetite control. Ghrelin is an appetite-stimulating hormone considered to promote obesity. Thus, we examined whether gastric stretching affects ghrelin secretion. We investigated the role of transient receptor potential vanilloid 4 (TRPV4) in gastric glands in the regulation of ghrelin secretion. TRPV4 immunostaining was performed in tissue samples from 57 patients who underwent gastrectomy. TRPV4 expression was compared between patients with (body mass index (BMI) ≥ 30) and without (BMI <30) obesity. For in vitro experiments, we used MGN3-1 cells, a ghrelin-producing cell line derived from mice. To investigate the bioactivity of TRPV4, MGN3-1 cells were treated with TRPV4 agonists and antagonists, and changes in intracellular Ca2+ concentration were confirmed. The concentration of ghrelin in the cell supernatant was measured using the ELISA with and without 120% stretch stimulation. TRPV4 expression was significantly higher in patients with obesity than in those without at all sites, except the fornix. Immunostaining confirmed the expression of TRPV4 in MGN3-1 cells. TRPV4 agonist administration increased intracellular Ca2+ concentration and ghrelin secretion in MGN3-1 cells, whereas the administration of the agonist combined with the antagonist decreased intracellular Ca2+ concentration and ghrelin secretion. Ghrelin secretion significantly increased in response to a 120% stretch in MGN3-1 cells. However, secretion was not increased by stretch when cells were treated with a TRPV4 antagonist. TRPV4 regulates ghrelin secretion in response to stretch in the stomach, which may affect body weight.