Obesity and malnutrition are associated with different inflammation patterns in rats
Darko Stevanovic1, Dragan Micic2, Mirjana Sumarac-Dumanovic2, Dejan Nesic1, Vera Popovic2, Vesna Starcevic1 & Vladimir Trajkovic3
The inflammatory response in rat models of obesity and malnutrition was examined. Rats received standard chow (control), chow enriched with 30% lard (obese) or 70, 50, 40 and 40% of expected food intake weekly for 4 weeks (starved). The serum levels of cytokines were determined by ELISA, while the expression of cytokine mRNA in heart and liver was analyzed by real-time RT-PCR. The blood concentrations of pro-inflammatory cytokines (TNF, IL-1) and Th1 cytokine IFN-gamma were significantly higher in starved compared to control rats, while no change was observed in the levels of anti-inflammatory TGF-beta. In contrast, TGF-beta, but not TNF, IL-1 or IFN-gamma, was significantly higher in blood of obese versus control rats. In the heart, the mRNA encoding TNF and IL-1 was increased to similar extent in starved and obese rats. The expression of Th1 cytokine IFN-gamma and Th17 cytokines IL-17 and IL-23p19 was increased in both starved and obese rats. However, while the concentration of IFN-gamma mRNA was higher in starved vs. obese rats, the expression of IL-17 and IL-23p19 mRNA was significantly elevated in obese vs starved rats. Accordingly, the mRNA levels of Th17-inducing TGF-beta were significantly increased in the hearts of obese, but not starved animals. No change in cytokine mRNA expression was observed in the livers of either starved or obese rats. In conclusion, malnutrition is associated with an increase in classic pro-inflammatory mediators (TNF, IL-1) and IFN-gamma-controlled Th1 response, while production of Th17 cytokines IL-17, IL-23 and TGF-beta is preferentially stimulated in obesity.