ABSTRACT Objective Obesity, or excessive body fat, is a significant health risk factor. Western diets (WD) contribute to metabolic dysfunction and obesity, while Mediterranean diets (MD) improve metabolic health. This study examined the contrasting effects of WD versus MD on visceral and subcutaneous adipose tissues (VAT, SAT) using a randomized preclinical trial in 38 female cynomolgus macaques assigned to consume either WD ( n = 21) or MD ( n = 17) for 31 months. Methods Body composition, metabolic parameters, and adipose transcriptomics were evaluated. Results WD significantly induced VAT and SAT accumulation, which was directly associated with insulin resistance, hepatosteatosis, and time spent alone and inversely related to cortisol suppression response to dexamethasone indicating hypothalamic–pituitary glucocorticoid insensitivity. Diet significantly influenced the VAT transcriptome, with MD upregulating pathways linked to RNA processing and protein folding while downregulating those involved in fatty acid oxidation and aerobic respiration. Conclusions These findings highlight the protective role of MD against fat accumulation and metabolic dysfunction and provide novel insights into the molecular mechanisms underlying diet‐induced obesity. Promoting this dietary pattern may help reduce obesity and chronic disease risk. Further research integrating proteomics and metabolomics is required to better understand diet‐induced molecular changes.
Abu-sheikha et al. (Wed,) studied this question.