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Liraglutide Promotes Browning of White Adipose Tissue in Mice with Diet Induced Obesity
Author(s) -
Oliveira Fernanda Cerqueira Barroso,
Ribeiro Carolina Martins,
Christ Camila Greice,
Pereira Sidney Alcântara,
Beserra Bruna Teles Soares,
Costa Silva Viana Janice,
Assis Rocha Neves Francisco,
Coelho Michella Soares,
Amato Angélica Amorim
Publication year - 2017
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.31.1_supplement.886.1
Subject(s) - liraglutide , endocrinology , medicine , white adipose tissue , brown adipose tissue , thermogenesis , agonist , adipose tissue , type 2 diabetes , weight loss , weight gain , fgf21 , diet induced obese , obesity , diabetes mellitus , receptor , insulin resistance , body weight , fibroblast growth factor
Liraglutide is a long‐acting glucagon‐like peptide 1 (GLP‐1) receptor agonist used as an anti‐hyperglycemiant agent in type 2 diabetes and recently approved as an anti‐obesity agent. The mechanisms underlying weight loss include delayed gastric emptying and induction of satiety, and there are data indicating it may also result in increased energy expenditure. Beige adipocytes are an inducible cell type in white adipose tissue (WAT), in a process so‐called browning of WAT. Upon appropriate stimuli, beige adipocytes are fully capable of executing thermogenesis. Objective To investigate the effects of liraglutide on browning of WAT in obese mice. Methods Male C57Bl/6 mice with obesity induced by high fat diet (HFD) were randomly assigned into four groups and treated with saline (vehicle), the b3‐adrenergic agonist CL316,243, liraglutide or liraglutide and CL316,243. Liraglutide was administered intraperitoneally for 21 days (200 μg/kg, twice daily) and CL316,243 was administered intraperitoneally from day 17 to day 21 (1 mg/kg/d, once daily, for 5 days). Weight gain, energy intake and metabolic efficiency were determined. Two different WAT (inguinal and epidydimal) and the interscapular brown adipose tissue (BAT) depots were excised for determination of adiposity, histological analysis, oxygen consumption rates and relative expression of Ucp‐1 by RT‐qPCR. Results ( p <0.05, ~ 5 mice/group): Liraglutide treatment reduced HFD‐induced body weight gain, energy intake, metabolic efficiency, visceral and subcutaneous adiposity (epidydimal and inguinal WAT depots), when compared to saline treatment. BAT mass decreased only in response to treatment with CL316,243, either alone or in combination with liraglutide. In all three adipose tissue depots, liraglutide treatment induced the expression of Ucp‐1 when compared to saline, and this effect was additive to that of treatment with CL316,243. Liraglutide significantly increased oxygen consumption rates in epidydimal WAT and interscapular BAT, compared saline treatment. In addition, in epidydimal WAT, inguinal WAT and interscapular BAT, the effect of liraglutide on oxygen consumption was additive to that of CL316,243 stimulation. Conclusion Our findings suggest that liraglutide treatment induces browning of WAT and increases the thermogenic capacity of both WAT and BAT. In addition, its effects seem additive to those of b3‐adrenergic signalling, a classical pathway of adaptive thermogenesis activation. This suggests that GLP‐1 receptor agonists may result in increased energy expenditure by activating thermogenic adipocytes, in addition to decreasing food intake, and opens new horizons to treat obesity. Support or Funding Information CNPq/CAPES/FAPDF