Fish oil decreases inflammation and reduces cardiac remodeling in rosiglitazone treated aging mice

Clinical studies suggest that rosiglitazone (RSG) treatment may increase the incidence of heart failure in diabetic patients. In this study, we examined whether a high corn oil diet with RSG treatment in insulin resistant aging mice exerted metabolic and pro-inflammatory effects that stimulate cardiac dysfunction. We also evaluated whether fish oil attenuated these effects. Female C57BL/6J mice (13 months old) were divided into 5 groups: (1) lean control (LC), (2) corn oil, (3) fish oil, (4) corn oil + RSG and (5) fish oil + RSG. Mice fed a corn oil enriched diet and RSG developed hypertrophy of the left ventricle (LV) and decreased fractional shortening, despite a significant increase in total body lean mass. In contrast, LV hypertrophy was prevented in RSG treated mice fed a fish oil enriched diet. Importantly, hyperglycemia was controlled in both RSG groups. Further, fish oil + RSG decreased LV expression of atrial and brain natriuretic peptides, fibronectin and the pro-inflammatory cytokines interleukin-6 and tumor necrosis factor-α, concomitant with increased interleukin-10 and adiponectin levels compared to the corn oil + RSG group. Fish oil + RSG treatment suppressed inflammation, increased serum adiponectin, and improved fractional shortening, attenuating the cardiac remodeling seen in the corn oil + RSG diet fed C57BL/6J insulin resistant aging mice. Our results suggest that RSG treatment has context-dependent effects on cardiac remodeling and serves a negative cardiac role when given with a corn oil enriched diet.

Graphical abstractProposed mechanism of the effect of chronic supplementation of a pro-inflammatory corn oil diet with rosiglitazone (RSG) on cardiac remodeling. RSG exacerbated pathological LV hypertrophy and dysfunction in aging C57BL/6J mice. When dietary corn oil was supplemented with fish oil, RSG exerted anti-inflammatory effects and prevented LV hypertrophy and dysfunction.Figure optionsDownload full-size imageDownload as PowerPoint slide