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Adipose tissue and vascular phenotypic modulation by voluntary physical activity and dietary restriction in obese insulin resistant OLETF rats

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AJP Regulatory Integrative and Comparative Physiology

Published online on

Abstract

Adipose tissue (AT)-derived cytokines are proposed to contribute to obesity-associated vascular insulin resistance. We tested the hypothesis that voluntary physical activity and diet restriction-induced maintenance of body weight would both result in decreased AT inflammation and concomitant improvements in insulin-stimulated vascular relaxation in the hyperphagic, obese OLETF rat. Rats (age 12 wk) were randomly assigned to sedentary (SED, n=10), wheel running (WR, n=10), and diet restriction (DR, n=10; fed 70% of SED) for 8 weeks. WR and DR rats exhibited markedly lower adiposity (7.1±0.4 and 15.7±1.1% body fat, respectively) relative to SED (27±1.2% body fat), as well as improved blood lipid profiles and systemic markers of insulin resistance. Reduced adiposity in both WR and DR was associated with decreased AT mRNA expression of inflammatory genes (e.g., MCP-1, TNF-α, IL-6) and markers of immune cell infiltration (e.g., CD8, CD11c, F4/80). The extent of these effects were most pronounced in visceral AT compared to subcutaneous and periaortic AT. Markers of inflammation in brown AT were upregulated with WR but not DR. In periaortic AT, WR and DR-induced reductions in expression and secretion of cytokines were accompanied with a more athero-protective gene expression profile in the adjacent aortic wall. WR, but not DR, resulted in greater insulin-stimulated relaxation in the aorta; an effect that was in part mediated by a decrease in insulin-induced endothelin-1 activation in WR aorta. Collectively, we show in OLETF rats that lower adiposity leads to less AT and aortic inflammation as well as an exercise-specific improvement in insulin-stimulated vasorelaxation.