Melatonin supplementation in obese mothers reduces hypothalamic inflammation and enhances thermogenesis in mice progeny

Maternal obesity might induce obesity and metabolic alterations in the progeny. The study aimed to determine the effect of supplementing obese mothers with Mel (Mel) on thermogenesis and inflammation. C57BL/6 female mice (mothers) were fed from weaning to 12 weeks control diet (C, 17% kJ as fat) or a high-fat diet (HF, 49% kJ as fat) and then matted with male mice fed the control diet. Melatonin (10 mg/kg daily) was supplemented to mothers during gestation and lactation, forming the groups C, CMel, HF, and HFMel (n = 10/group). Twelve-week male offspring were studied (plasma biochemistry, immunohistochemistry, protein, and gene expressions at the hypothalamus - Hyp, subcutaneous white adipose tissue - sWAT, and interscapular brown adipose tissue - iBAT). Comparing HFMel vs. HF offspring, fat deposits and plasmatic proinflammatory markers decreased. Also, HFMel showed decreased Hyp proinflammatory markers and neuropeptide Y (anabolic) expression but improved proopiomelanocortin (catabolic) expression. Besides, HFMel sWAT adipocytes changed to a beige phenotype with-beta-3 adrenergic receptor and uncoupling protein-1 activation, concomitant with browning genes activation, triggering the iBAT thermogenic activity. In conclusion, compelling evidence indicated the beneficial effects of supplementing obese mothers with Mel on the health of their mature male offspring. Mel led to sWAT browning-related gene enhancement, increased iBAT thermogenis, and mitigated hypothalamic inflammation. Also, principal component analysis of the data significantly separated the untreated obese mother progeny from the progeny of treated obese mothers. If confirmed in humans, the findings encourage a future guideline recommending Mel supplementation during pregnancy and breastfeeding. Melatonin supplemented to obese mothers benefits their adult male offspring: mitigating hypothalamic proinflammatory cytokines, activating browning in subcutaneous adipose tissue, and reducing whitening in interscapular brown adipose tissue (arrow-up means to increase, and arrow-down means to decrease). Abbreviations: Adrb3, Adrenergic receptor-beta 3; Bmp8b, Bone morphogenetic protein 8b; Cidea, Cell death-inducing DNA fragmentation factor-alpha subunit-like effector A; Cpt1b, carnitine palmitoyl transferase 1b; iBAT, interscapular brown adipose tissue; MT1, Melatonin receptor 1; MT2, Melatonin receptor 1B; NFKB, Nuclear factor-kappa B; NPY, Neuropeptide Y; Nrf1, Nuclear respiratory factor 1; POMC, Pr