Objective: This study was designed to test whether adiponectin plays a role in diet‐induced obesity and insulin resistance and acts as a mediator to induce or inhibit specific metabolic pathways involved in lipid metabolism

Research Methods and Procedures: Forty C57BL/6J male mice were fed either a high‐fat (HF) or control diet for 4 months, and adiponectin, its receptors, and enzyme expression in liver and muscle tissue were measured.

Results: Mice fed the HF diet exhibited significantly greater weight gain, abnormal oral glucose tolerance test curves, and elevated homeostasis model assessment of insulin resistance (5.3 ± 0.89 vs. 2.8 ± 0.39). A significant reduction of adiponectin RNA expression (51%) and protein levels (15%) was observed in the adipose tissue of HF animals; however, serum adiponectin levels did not differ between groups (7.12 ± 0.34 μg/mL vs. 6.44 ± 0.38 μg/mL). Expression of hepatic mRNA of AdipoR1 and AdipoR2 was reduced by 15% and 25%, respectively, in animals fed the HF diet. In contrast, receptor mRNA expression of AdipoR1 and AdipoR2 increased by 25% and 30%, respectively, in muscle tissue. No effect was found on hepatic adenosine monophosphate‐activated protein kinase expression; however, a significant reduction of phosphoadenosine monophosphate kinase levels in muscles was observed. Hepatic acetyl‐coenzyme A carboxylase was similar between groups, but in muscles, the inactive form phosphoacetyl‐coenzyme A carboxylase was significantly reduced (p < 0.05).

Discussion: The HF diet led to decreased insulin sensitivity accompanied by impaired activity of adiponectin‐related enzymes in skeletal muscles but not in the liver. These results suggest that the HF diet has a tissue‐specific effect on adiponectin and associated enzyme expression.