Full Title: In vivo mouse model for examining contribution of inflammation to development of obesity and diabetes
Journal: FASEB J
Year of Publication: 2012
Publication Author(s): Komarnytsky S, Esposito D, Raskin I
An adipose tissue-mediated shift to production of proinflammatory cytokines in obesity likely contributes to the low-level systemic inflammation that is seen in metabolic syndrome-associated chronic pathologies such as diabetes. The mechanism explaining this relationship remains unknown. In this study, we present specific details on using pharmacological supplementation with triptolide, a diterpene triepoxide with anti-inflammatory and immunosuppressive properties, to diet-induced obese (DIO) C57BL/6J male mice. Animals received 50 ug/kg of triptolide in corn oil (vehicle) via oral gavage every 3 d for 9 wk and underwent oral glucose tolerance test on wk 1 (baseline), wk 7 and wk 9. Significant increase in glucose utilization and improved insulin sensitivity were associated with triptolide in the absence of the direct effects on obesity measures of food intake, body weight, or composition. Macrophage recruitment and cytokine signature of the adipose tissue were significantly reduced by triptolide with minimal or no effect on the adipose humoral factors leptin and adiponectin. These data demonstrate that DIO-triptolide mouse is a tractable animal model for the study of obesity-related metabolic dysfunction and chronic inflammation. The study was supported in part by the 5P50AT002776-05 grant from NCCAM.