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GQ‐16, a novel partial PPARγ ligand, decreases visceral adiposity and induces the expression of thermogenesis‐related genes in mice with obesity and insulin resistance induced by diet (1160.8)
Author(s) -
Coelho Michella,
Lima Caroline,
Royer Carine,
Pitta Ivan,
Amato Angélica,
Neves Francisco
Publication year - 2014
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.28.1_supplement.1160.8
Subject(s) - medicine , endocrinology , thermogenesis , insulin resistance , rosiglitazone , adipose tissue , brown adipose tissue , weight gain , type 2 diabetes , downregulation and upregulation , peroxisome proliferator activated receptor , obesity , diet induced obese , white adipose tissue , insulin , receptor , chemistry , diabetes mellitus , body weight , gene , biochemistry
Thiazolidinediones are used for the treatment of type 2 diabetes (T2DM) and their therapeutic actions are mediated via activation of PPARγ. Despite their efficacy, their use is limited by side effects such as weight gain. We have previously identified a novel PPARγ ligand with similar anti‐diabetic efficacy as rosiglitazone (RSG), but without weight gain. Objective: To evaluate the effects of different doses of GQ‐16 on adiposity and gene expression in mice with insulin resistance and obesity induced by diet. Methods: Mice were fed normal‐fat (NFD) or high‐fat (HFD) diet since weaning. At the age of 16 wk, they received GQ‐16 (5, 10 or 20mg/kg/d), RSG (4mg/kg/d) or vehicle by gavage. White adipose tissue (WAT) pads were excised for determination of adiposity and gene expression by qPCR. Results (P<0.05, 4 mice/group): In HFD‐treated mice, weight gain was reduced by treatment with 5, 10 and 20 mg/kg/d of GQ‐16, but increased by RSG. GQ‐16 (10 and 20 mg/kg/d) decreased blood glucose similarly to RSG. In addition, GQ‐16 treatment (20 mg/kg/d) reduced WAT pads, whereas RSG treatment increased them. Brown fat‐selective genes were upregulated in WAT in response to GQ‐16. Conclusions: Lower doses of GQ‐16 decreased blood glucose and visceral adiposity. This latter finding might possibly reflect increased thermogenesis, since GQ‐16 induced the expression of thermogenesis‐related genes, and reinforces the potential of GQ‐16 as a new strategy to treat obese patients with T2DM. Grant Funding Source : CNPq