Aerobic exercise training combined with enalapril treatment improves obesity-induced brown adipose tissue whitening

Interscapular brown adipose tissue (iBAT) whitening is characterized by thermogenic dysfunction and may aggravate the metabolic complications of obesity. Moreover, whitening is linked to multiple factors, including the overactivation of the classical renin-angiotensin system (RAS) arm. Thus, we aim to compare the impact of RAS modulation by enalapril and/or aerobic exercise training (AET) in obesity-induced iBAT whitening. C57BL/6 mice were fed a standard chow (SC) or high-fat (HF) diet for 16 weeks. After 8 weeks, the HF animals were subdivided (n = 10 for each group): HF, HF + Enalapril (HF-E), HF + Training (HF-T), and HF + Enalapril + Training (HF-ET). We evaluated: body mass (BM) gain, adiposity index, iBAT morphology, RAS components, and thermogenic markers in iBAT. The HF group exhibited increased body adiposity, iBAT mass, and lipid content, as evidenced by a collapse in iBAT thermogenic capacity and overactivation of the classical RAS arm (AT1R) compared to the SC group. All interventions reduced body adiposity and iBAT mass, improved thermogenic capacity (UCP1, Vegfa, and AMPK), and shifted iBAT RAS balance to the counter-regulatory arm (MasR and MrgD). HF-E improved iBAT morphology and brown adipogenesis (Prdm16 and Cidea) compared to the HF group. HF-T improved mitochondrial biogenesis (PGC1α and Tfam) compared to the HF group. HF-ET showed additional reduced body adiposity by sympathetic activation (β3-ar) and increased brown adipocyte competence (AMPK, Tfam, and Cidea) compared to SC and HF groups. We concluded that combined interventions (enalapril and AET) have an additional impact on iBAT whitening, enhancing brown morphology and thermogenic capacity in obese mice.