High fasting ghrelin concentrations are related to low fatty acid flux in overweight subjects

Abstract

Ghrelin plays a role in glucose metabolism. Given the competitive interaction between free fatty acids (FFA) and glucose as fuel sources, the present study determined relationships between acylghrelin and postprandial metabolism in overweight, nondiabetic Hispanic and African American men and women (n=19, BMI 34.8 ± 6.7 kg/m2, 47.1 ± 9.3 yrs). Subjects were admitted for 24 h and consumed a 40g‐fat meal test. Blood metabolite and hormones profiles were determined biochemically, substrate oxidation by indirect calorimetry, insulin sensitivity by IVGTT, and FFA flux by stable isotope infusion and GC/MS. Fasting ghrelin was negatively correlated with fasting insulin (r = −0.47, P = 0.04) and FFA flux (r = −0.55, P = 0.03); it tended to be positively related to glucose oxidation (r = +0.46, P = 0.06). After the meal, the absolute fall in ghrelin correlated with fasting ghrelin (r = +0.88, P < 0.001) suggesting a biological limit of activity. The % decrease in ghrelin correlated positively with insulin sensitivity (r = +0.47, P = 0.04) and fasting TG (r = +0.53, P = 0.02). These data suggest that in overweight subjects, high fasting ghrelin signals efficient glucose use, lower FFA flux, and allows for greater postprandial ghrelin reduction. The connection between ghrelin and fasting FFA flux and TG suggests its role in body weight regulation is mediated through FFA metabolism, as well as though glucose metabolism.