Diet-induced Fasting Ghrelin Elevation Reflects the Recovery of Insulin Sensitivity and Visceral Adiposity Regression

Abstract

Abstract Context Lower fasting ghrelin levels (FGL) are associated with obesity and metabolic syndrome. Objective We aimed to explore the dynamics of FGL during weight loss and its metabolic and adiposity-related manifestations beyond weight loss. Methods This was a secondary analysis of a clinical trial that randomized participants with abdominal obesity/dyslipidemia to 1 of 3 diets: healthy dietary guidelines (HDG), Mediterranean diet (MED), or green-MED diet, all combined with physical activity (PA). Both MED diets were similarly hypocaloric and included 28 g/day walnuts. The green-MED group further consumed green tea (3-4 cups/day) and a Wolffia globosa (Mankai) plant green shake. We measured FGL and quantified body fat depots by magnetic resonance imaging at baseline and after 18 months. Results Among 294 participants (body mass index = 31.3 kg/m2; FGL = 504 ± 208 pg/mL; retention rate = 89.8%), lower FGL was associated with unfavorable cardiometabolic parameters such as higher visceral adipose tissue (VAT), intrahepatic fat, leptin, and blood pressure (P < 0.05 for all; multivariate models). The ∆FGL18-month differed between men (+7.3 ± 26.6%) and women (−9.2% ± 21.3%; P = 0.001). After 18 months of moderate and similar weight loss among the MED groups, FGL increased by 1.3%, 5.4%, and 10.5% in HDG, MED, and green-MED groups, respectively (P = 0.03 for green-MED vs HDG); sex-stratified analysis revealed similar changes in men only. Among men, FGL18-month elevation was associated with favorable changes in insulin resistance profile and VAT regression, after adjusting for relative weight loss (HbA1c: r = −0.216; homeostatic model of insulin resistance: r = −0.154; HDL-c: r = 0.147; VAT: r = −0.221; P < 0.05 for all). Insulin resistance and VAT remained inversely related with FGL elevation beyond that explained by weight loss (residual regression analyses; P < 0.05). Conclusion Diet-induced FGL elevation may reflect insulin sensitivity recovery and VAT regression beyond weight loss, specifically among men. Green-MED diet is associated with greater FGL elevation.