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

Abstract:

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.

journal_name

Endocrine

journal_title

Endocrine

authors

Graus-Nunes F,Rachid TL,de Oliveira Santos F,Barbosa-da-Silva S,Souza-Mello V

doi

10.1007/s12020-016-1213-1

subject

Has Abstract

pub_date

2017-03-01 00:00:00

pages

786-798

issue

3

eissn

1355-008X

issn

1559-0100

pii

10.1007/s12020-016-1213-1

journal_volume

55

pub_type

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