Effect of different doses of GQ-16, a novel partial PPAR&gamma ligand, on metabolic parameters in mice with obesity and insulin resistance induced by high fat diet

Program: Abstracts - Orals, Featured Poster Presentations, and Posters
Session: SUN 780-806-Determinants of Insulin Resistance & Associated Metabolic Disturbances
Basic/Translational
Sunday, June 16, 2013: 1:45 PM-3:45 PM
Expo Halls ABC (Moscone Center)

Poster Board SUN-806
Michella Soares Coelho*1, Laise A. Morais1, Carine Royer1, Suely Lins Galdino2, Ivan da Rocha Pitta2, Francisco de Assis Rocha Neves1 and Angelica Amorim Amato1
1University of Brasilia, Brasilia, Brazil, 2University of Pernambuco, Pernambuco, Brazil
Thiazolidinediones (TZDs) were extensively used for the treatment of type 2 diabetes (T2D), and their therapeutic actions are mediated via activation of peroxisome proliferator-activated receptor γ (PPARγ). Despite their clinical effectiveness, their use is limited by side effects such as weight gain, edema and bone loss, in addition to increased risk of cardiac mortality with rosiglitazone (ROSI). This has prompted the search for novel PPARγ agonists with reduced side effects. We have previously described a novel partial PPARγ ligand (QG-16) with similar anti-diabetic efficacy as ROSI, yet in the absence of weight gain, in obese and insulin-resistant mice treated for two weeks with 20 mg/kg/d of GQ-16. The aim of this study was to evaluate the effects of different doses of GQ-16 on metabolic parameters and in mice with insulin resistance and obesity induced by high fat diet (HFD). Mice were fed a normal-fat diet (NFD, 10% kcal fat) or HFD (60% kcal fat - Harlan Teklad) since weaning. At the age of 18 wk, mice were randomly assigned into six groups and received GQ-16 (5, 10 or 20mgkgd), ROSI (4mgkgd) or vehicle by gavage daily for two weeks (groups: NFD, HFD, HFD+ROSI, HFD+QG+5, HFD+GQ+10 or HFD+GQ+20). Body weight (BW), BW gain, food and water intake, energy intake, metabolic efficiency, and fasting blood glucose were measured daily or weekly. White adipose tissue (WAT) fat pad was excised and weighed for determination of adiposity. Results (P<0.05,~4 micegroup): As expected, BW, BW gain, WAT fat mass content, blood glucose and food intake were greater in the HFD group (BW: 67.4±2.2) compared to the NFD group (BW: 51.8±2.6g). Interestingly, GQ-16 treatment reduced BW and WAT fat pads in the HFD+GQ+20 group (BW: 45.9±3.2g), whereas ROSI treatment increased it (HFD+ROSI group, 74.1±3.6g). In mice that received HFD, weight gain was significantly reduced in all groups that treated with GQ-16, but increased by ROSI treatment. Additionally, GQ-16 decreased blood glucose similarly to ROSI in the HFD+GQ+10 (91.3±1.4) and HFD+GQ+20 groups (85±5.5), when compared to the HFD group (123±6.4mgdL). Our data indicate that lower doses of GQ-16 decrease blood glucose and visceral adiposity, and modify body weight in mice with obesity and insulin resistance induced by HFD. These results reinforce the more favorable effects of GQ-16 treatment on weight, as compared to ROSI, and hence the potential of this compound as a new strategy to treat obese patients with T2DM.

Nothing to Disclose: MSC, LAM, CR, SLG, IDRP, FDARN, AAA

*Please take note of The Endocrine Society's News Embargo Policy at http://www.endo-society.org/endo2013/media.cfm

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