Endocrine DOI 10.1007/s12020-016-1213-1 ORIGINAL ARTICLE AT1 receptor antagonist induces thermogenic beige adipocytes in the inguinal white adipose tissue of obese mice Francielle Graus-Nunes 1 ● Tamiris Lima Rachid 1 ● Felipe de Oliveira Santos 1 ● Sandra Barbosa-da-Silva 1 ● Vanessa Souza-Mello 1 Received: 2 September 2016 / Accepted: 15 December 2016 © Springer Science+Business Media New York 2016 Abstract Purpose To evaluate whether losartan is able to induce beige adipocytes formation, focusing on the thermogenic gene expression and adipocyte remodeling in the sub- cutaneous white adipose tissue of diet-induced obese mice. Methods Male C57BL/6 mice received a control diet (10% energy as lipids) or a high-fat diet (50% energy as lipids) for 10 weeks, followed by a 5-week treatment with losartan: control group, control-losartan group (10 mg/Kg/day), high- fat group and high-fat-losartan group (10 mg/Kg/day). Biochemical, morphometrical, stereological and molecular approaches were used to evaluate the outcomes. Results The high-fat diet elicited overweight, insulin resistance and adipocyte hypertrophy in the high-fat group, all of which losartan rescued in the high-fat-losartan group. These effects comply with the induction of beige adipocytes within the inguinal fat pads in high-fat-losartan group as they exhibited the greatest energy expenditure among the groups along with the presence uncoupling protein 1 posi- tive multilocular adipocytes with enhanced peroxisome proliferator-activated receptor gamma coactivator 1-alpha and PR domain containing 16 mRNA levels, indicating a significant potential for mitochondrial biogenesis and adaptive thermogenesis. Conclusions Our results show compelling evidence that losartan countered diet-induced obesity in mice by enhan- cing energy expenditure through beige adipocytes induc- tion. Reduced body mass, increased insulin sensitivity, decreased adipocyte size and marked expression of uncou- pling protein 1 by ectopic multilocular adipocytes support these findings. The use of losartan as a coadjutant medicine to tackle obesity and its related disorders merits further investigation. Keywords Losartan ● Beige adipocyte ● Inguinal fat ● Obesity ● UCP1 ● PRDM16 Introduction Lipotoxicity underpins obesity and its comorbidities onset [1]. White adipose tissue (WAT) undergoes severe hyper- trophy and hyperplasia as a positive energy balance is established, triggering insulin resistance (IR) and pro- inflammatory adipokine release [2]. In the long run, WAT becomes unable to buffer the excessive free fatty acids, which are driven to ectopic depots, impairing organs functioning and maximizing IR [3]. A viable strategy to tackle obesity and its metabolic alterations is to enhance energy expenditure (EE) by stimulating adaptive thermo- genesis [4]. EE encompasses three elements: obligatory (to keep normal functioning of cells and organs), physical activity and adaptive thermogenesis (shivering or non-shivering) [5]. Non-shivering thermogenesis (NST), the potential to dissipate surplus energy intake into heat, has been con- sidered as an exclusive feature of brown adipose tissue (BAT). However, recent evidences show that ectopic uncoupling protein 1 (UCP1) expression along with a gene expression profile similar to brown adipocytes induces subcutaneous WAT (sWAT) to acquire BAT features * Vanessa Souza-Mello souzamello.uerj@gmail.com 1 Laboratory of Morphometry, Metabolism and Cardiovascular disease, Biomedical Centre, Institute of Biology, State University of Rio de Janeiro, Rio de Janeiro, Brazil