High fat feeding leads to inflammation and depressed markers of immune system reactivity in rats

Abstract

Increased adiposity is strongly associated with inflammation. Prior studies have shown that feeding rats a high fat diet (HFD) leads to increased adiposity and inflammation, including elevated circulating tumor necrosis factor alpha (TNFα). The current study was designed to further examine whether markers of inflammation and immune system activation are altered in HFD rats. Rats were fed either a normal chow or HFD for 6 weeks. Comparative whole transcriptome sequencing of isolated aorta from HFD and chow fed rats indicates a significant (p<0.05) 2.8‐fold decrease in the expression of interferon regulatory factor 4 (IRF4), a factor required for lymphocyte activation, suggesting the immune system of these animals is downregulated. Results from western blot analyses show no difference in the expression of the anti‐inflammatory heat shock proteins 60 or 70 (HSP60/70) in erythrocytes or plasma from HFD rats compared to rats fed normal chow (p>0.05). Unlike TNFα, urinary levels of the inflammatory mediator prostaglandin E2 are not different between HFD and chow rats (p>0.05). These findings suggest that, despite elevations in TNFα, the immune system of HFD rats may be partly downregulated. Further studies testing the agglutination response of plasma samples collected from HFD and chow rats will help to assess how well circulating leukocytes respond to immune challenges in overweight animals.