Abstract
Rosiglitazone, a potent ligand for peroxisome proliferator activated-receptor gamma (PPARγ ), is commonly used in the treatment of type 2 diabetes. As an insulin sensitizer, rosiglitazone (ROSI) improves hyperglycemia and insulin resistance yet causes increased adipose mass and weight gain in mice and humans. The adipogenic effect of rosiglitazone is through activation of PPARγ. Conjugated linoleic acid (CLA) is a natural ligand for PPARα and PPARβ and reduces adipose mass and body weight gain in mice. The hypothesis of this study is that feeding CLA attenuates the effect of ROSI on weight gain in obese mice. Ob/Ob male mice were randomly assigned into four treatment groups: Control diet (CON; 6.5% fat) or a diet supplemented with 1.5% CLA (CLA) and intraperitoneally injected daily with either PBS or 10mg/kg ROSI for 2 weeks. An insulin tolerance test was performed 13 days after commencement of treatment. ROSI induced rapid weight gain after 13 days of treatment (p<0.05) regardless of diet. The combination of CLA-ROSI and ROSI treatment alone sustained elevated adiponectin levels and resulted in reduced fasting glucose, serum insulin, NEFA. Dietary supplementation of CLA alone significantly prevented weight gain, reduced adipose tissue mass (p<0.05) and slightly prevented weight gain in ROSI-treated mice. In the liver, CLA significantly decreased ROSI-induced TG levels (p<0.05) and PPARγ protein. Our observations demonstrate that combined treatment of rosiglitazone and dietary CLA improves lipid profiles and hyperinsulinemia in Ob/Ob mice. These data suggest a potential role of CLA to complement therapy with ROSI for the management of type 2 diabetes.
Published Version
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