title: AT1 receptor antagonist induces thermogenic beige adipocytes in the inguinal white adipose tissue of obese mice.
abstract: OBJECTIVE
  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.
authors.affiliation: Laboratory of Morphometry, Metabolism and Cardiovascular disease, Biomedical Centre, Institute of Biology, State University of Rio de Janeiro, Rio de Janeiro, Brazil.
authors.forename: Francielle
authors.initials: F
authors.lastname: Graus-Nunes
authors.affiliation: Laboratory of Morphometry, Metabolism and Cardiovascular disease, Biomedical Centre, Institute of Biology, State University of Rio de Janeiro, Rio de Janeiro, Brazil.
authors.forename: Tamiris Lima
authors.initials: TL
authors.lastname: Rachid
authors.affiliation: Laboratory of Morphometry, Metabolism and Cardiovascular disease, Biomedical Centre, Institute of Biology, State University of Rio de Janeiro, Rio de Janeiro, Brazil.
authors.forename: Felipe
authors.initials: F
authors.lastname: de Oliveira Santos
authors.affiliation: Laboratory of Morphometry, Metabolism and Cardiovascular disease, Biomedical Centre, Institute of Biology, State University of Rio de Janeiro, Rio de Janeiro, Brazil.
authors.forename: Sandra
authors.initials: S
authors.lastname: Barbosa-da-Silva
authors.affiliation: Laboratory of Morphometry, Metabolism and Cardiovascular disease, Biomedical Centre, Institute of Biology, State University of Rio de Janeiro, Rio de Janeiro, Brazil. souzamello.uerj@gmail.com.
authors.forename: Vanessa
authors.identifier: http://orcid.org/0000-0002-2510-9569
authors.initials: V
authors.lastname: Souza-Mello
mesh_terms: D000069797:Adipocytes, Beige / Q000187:drug effects* / Q000378:metabolism; D052436:Adipose Tissue, White / Q000187:drug effects* / Q000378:metabolism; D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D001786:Blood Glucose; D049108:Cell Enlargement / Q000187:drug effects*; D002149:Energy Intake / Q000187:drug effects; D006973:Hypertension / Q000188:drug therapy / Q000378:metabolism; D007333:Insulin Resistance / Q000502:physiology; D019808:Losartan / Q000494:pharmacology* / Q000627:therapeutic use; D051379:Mice; D009765:Obesity / Q000378:metabolism*
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D001786:Blood Glucose; D019808:Losartan
keywords: Beige adipocyte; Inguinal fat; Losartan; Obesity; PRDM16; UCP1