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: A secondary analysis of a clinical trial where we randomized participants with abdominal-obesity/dyslipidemia to one of three 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 28g/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=31.3kg/m 2;FGL=504±208pg/mL; retention rate=89.8%], lower FGL were associated with unfavorable cardiometabolic parameters as higher visceral-adipose-tissue (VAT), intra-hepatic fat, leptin, and blood pressure (p<0.05 for all; multivariate models). ∆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 which was explained by weight-loss (residual regression analyses; p<0.05).

Conclusions: 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.

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