Immunological and behavioral responses to in vivo lipopolysaccharide administration in young and healthy obese and normal-weight humans

•The behavioral responses to LPS was similar in obese and normal-weight subjects.•The cortisol response to LPS was attenuated in obese individuals and related to body fat.•Obesity per se is not associated with increased behavioral sensitivity to cytokines.•The hypothalamus functions might be disrupted in obesity.•Future studies will need to assess potential interaction of obesity with other factors. Obesity is associated with an increase prevalence of neuropsychiatric symptoms and diseases, such as depression. Based on the facts that pro-inflammatory cytokines are able to modulate behavior, and that obesity is characterized by a chronic low-grade inflammatory state, inflammation has been hypothesized to contribute to the neuropsychiatric comorbidity in obese individuals. However, a causal link between inflammation and the development of neuropsychiatric symptoms is hard to establish in humans. Here, we used an inflammatory stimulus, i.e. the intravenous injection of lipopolysaccharide (LPS), in a double-blind placebo-controlled design, to determine the vulnerability of obese individuals to inflammation-induced behavioral changes. The hypothesis was that obese individuals would show heightened behavioral response compared to normal-weight subjects for the same inflammatory stimulus, reflecting an increased sensitivity to the behavioral effects of pro-inflammatory cytokines. LPS (dose 0.8 ng/kg body weight, adjusted for estimated blood volume in obese subjects) and placebo (saline) were intravenously injected in 14 obese healthy subjects and 23 normal-weight healthy subjects in a within-subject, randomized, crossover design. LPS administration induced, in both groups, an acute increase in blood concentrations of cytokines (interleukin-6, tumor necrosis factor-α, and IL-10), as well as in body temperature, cortisol, norepinephrine, sickness symptoms, fatigue, negative mood, and state anxiety. There were little differences in the immune and behavioral responses to LPS between obese and normal-weight subjects, but the cortisol response to LPS was strongly attenuated in obese individuals. Higher percentage of body fat was related to a lower cortisol response to LPS. Taken together, the population of young and healthy obese individuals in this study did not exhibit an increased behavioral sensitivity to cytokines, but an attenuated cortisol response to the immune challenge. Future studies will need to determine whether additional physiological and psychological f