Ghrelin and its role on energy balance

Abstract

Obesity has increasedat an alarming rate in the United States over the past fewdecades and has reached epidemic proportion. Overall energy intake and expenditure are exquisitely matched over long periods of time, through the process of energy homeostasis. Exogenous ghrelin infusion centrally or peripherally, increases food intake and promotes adiposity by acting on its receptor in the hypothalamus. Ghrelin is predominantly produced in the stomach and to a lesser extent in the hypothalamus. Diets rich in carbohydrates and fats significantly reduce ghrelin levels in the blood. However, the direct role of nutrients on ghrelin and the role of hypothalamic ghrelin on energy balance are not known. Therefore, we investigated the direct role of nutrients on ghrelin in isolated stomach and the role of hypothalamic ghrelin and its receptor by knocking down their gene expression using RNA interference. We found that glucose and amino acids directly affected ghrelin release from the stomach. We also found that reduction in gene expression of ghrelin or its receptor in the paraventricular nucleus of the hypothalamus caused significant reduction in body weight without affecting food intakes. RNA interference of ghrelin or its receptor in the hypothalamus also caused a significant reduction in blood ghrelin levels. Therefore, it appears that ghrelin systems in the brain can selectively affect body weight loss independent of energy intake. However, the mechanism involved in this effect is not known, thus further studies are required to investigate this role of ghrelin on energy balance.