Journal
AMERICAN JOURNAL OF PHYSIOLOGY-REGULATORY INTEGRATIVE AND COMPARATIVE PHYSIOLOGY
Volume 311, Issue 4, Pages R779-R787Publisher
AMER PHYSIOLOGICAL SOC
DOI: 10.1152/ajpregu.00243.2016
Keywords
fatty-acid oxidation; subcutaneous and visceral fat; insulin resistance; lipolysis and fatty acid metabolism; CPT-1b inhibition
Categories
Funding
- Discovery Grant from the Natural Sciences and Engineering Research Council of Canada (NSERC)
- Canada Foundation for Innovation
- Ontario Research Fund award
- Elia Scholarship
- NSERC Alexander Graham Bell Canada Graduate Scholarship
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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.
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