Antilipolytic and antilipogenic effects of the CPT-1b inhibitor oxfenicine in the white adipose tissue of rats

Oxfenicine is a carnitine-palmitoyl transferase 1b (CPT-1b)-specific inhibitor that has been shown to improve whole body insulin sensitivity while suppressing fatty acid (FA) oxidation and increasing circulating FA. Because the white adipose tissue (WAT) is an organ that stores and releases FAs, this study investigated whether oxfenicine-induced inhibition of FA oxidation affected adiposity and WAT metabolism in rats fed either low (LF) or high-fat (HF) diets. Following 8 wk of dietary intervention, male Sprague-Dawley rats were given a daily intraperitoneal injection of oxfenicine (150 mg/kg body wt) or vehicle (PBS) for 3 wk. Oxfenicine treatment reduced whole body fat oxidation, body weight, and adiposity, and improved insulin sensitivity in HF-fed rats. All of these effects occurred without alterations in food intake, energy expenditure, and ambulatory activity. In vivo oxfenicine treatment reduced FA oxidation and lipolysis in subcutaneous inguinal (SC Ing) adipocytes, whereas glucose incorporation into lipids (lipogenesis) was significantly reduced in both SC Ing and epididymal (Epid) adipocytes. In summary, our results show that oxfenicine-induced inhibition of CPT-1b markedly affects WAT metabolism, leading to reduced adiposity through a mechanism that involves reduced lipogenesis in the SC Ing and Epid fat depots of rats.