AT1 receptor antagonist induces thermogenic beige adipocytes in the inguinal white adipose tissue of obese mice

• Published in: Endocrine 2017-03, Vol.55 (3), p.786-798
• Main Authors: Graus-Nunes, Francielle, Rachid, Tamiris Lima, de Oliveira Santos, Felipe, Barbosa-da-Silva, Sandra, Souza-Mello, Vanessa
• Format: Article
• Language: English
• Subjects: Adipocytes, Beige - drug effects; Adipocytes, Beige - metabolism; Adipose Tissue, White - drug effects; Adipose Tissue, White - metabolism; Angiotensin II Type 1 Receptor Blockers - pharmacology; Angiotensin II Type 1 Receptor Blockers - therapeutic use; Animals; Blood Glucose; Cell Enlargement - drug effects; Diabetes; Endocrinology; Energy Intake - drug effects; Humanities and Social Sciences; Hypertension - drug therapy; Hypertension - metabolism; Insulin Resistance - physiology; Internal Medicine; Losartan - pharmacology; Losartan - therapeutic use; Medicine; Medicine & Public Health; Mice; multidisciplinary; Obesity; Obesity - metabolism; Original Article; Science
• ISSN: 1355-008X; 1559-0100
• DOI: 10.1007/s12020-016-1213-1

Purpose To evaluate whether losartan is able to induce beige adipocytes formation, focusing on the thermogenic gene expression and adipocyte remodeling in the subcutaneous 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 positive 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 enhancing energy expenditure through beige adipocytes induction. Reduced body mass, increased insulin sensitivity, decreased adipocyte size and marked expression of uncoupling 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.