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Diet-induced fasting ghrelin elevation reflects the recovery of insulin sensitivity and visceral adiposity regression.

Tsaban, G., A. Yaskolka Meir, H. Zelicha, E. Rinott, A. Kaplan, A. Shalev, A. Katz, D. Brikner, M. Blüher, U. Ceglarek, M. Stumvoll, M.J. Stampfer, I. Shai, 2022. Diet-induced fasting ghrelin elevation reflects the recovery of insulin sensitivity and visceral adiposity regression. JCEM. 107(2):336–345.

Aims: Lower fasting-ghrelin-levels (FGL) are associated with obesity and metabolic syndrome. 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). ΔFGL18-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.