Obese mice exhibit an altered behavioural and inflammatory response to lipopolysaccharide

Abstract

Summary Obesity is associated with an increase in the prevalence and severity of infections. Genetic animal models of obesity (ob/ob and db/db mice) display altered centrally-mediated sickness behaviour in response to acute inflammatory stimuli such as lipopolysaccharide (LPS). However, the effect of diet-induced obesity (DIO) on the anorectic and febrile response to LPS in mice is unknown. This study therefore determined how DIO and ob/ob mice respond to a systemic inflammatory challenge. C57BL/6 DIO and ob/ob mice, and their respective controls, were given an intraperitoneal (i.p.) injection of LPS. Compared to controls, DIO and ob/ob mice exhibited an altered febrile response to LPS (100 μg/kg) over 8 h. LPS caused a greater and more prolonged anorexic effect in DIO mice, and in ob/ob mice, LPS induced a reduction in food intake and body weight at an earlier time point. These effects of LPS in obese mice were also seen after a fixed dose of LPS (5 μg). LPS (100 μg/kg) induced c-Fos protein expression in several brain nuclei of control mice, with fewer c-Fos-positive cells observed in the brains of obese mice. An altered inflammatory response to LPS was also observed in obese mice as changes in cytokine expression and release were detected in the plasma, spleen, liver and peritoneal macrophages. In summary, DIO and ob/ob mice displayed an altered behavioural response and cytokine release to systemic inflammatory challenge. These findings could help explain why obese humans show an increased sensitivity to infections.