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 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 factors interact with the state of obesity to increase the risk for inflammation-induced neuropsychiatric symptoms.

中文翻译：

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年轻和健康肥胖和正常体重人群对体内脂多糖给药的免疫和行为反应

肥胖与神经精神症状和疾病（如抑郁症）的患病率增加有关。基于促炎细胞因子能够调节行为以及肥胖以慢性低度炎症状态为特征的事实，已经假设炎症会导致肥胖个体的神经精神共病。然而，在人类中很难确定炎症与神经精神症状发展之间的因果关系。在这里，我们在双盲安慰剂对照设计中使用了炎症刺激，即静脉注射脂多糖 (LPS)，以确定肥胖个体对炎症引起的行为变化的脆弱性。假设是，对于相同的炎症刺激，与正常体重的受试者相比，肥胖个体会表现出更高的行为反应，这反映了对促炎细胞因子的行为影响的敏感性增加。LPS（剂量 0.8 ng/kg 体重，根据肥胖受试者的血容量调整）和安慰剂（生理盐水）在受试者内、随机、交叉设计中静脉注射给 14 名肥胖健康受试者和 23 名正常体重健康受试者。在两组中，LPS 给药均导致细胞因子（白介素-6、肿瘤坏死因子-α 和 IL-10）以及体温、皮质醇、去甲肾上腺素、疾病症状、疲劳、消极情绪的血液浓度急剧增加和状态焦虑。肥胖和正常体重受试者对 LPS 的免疫和行为反应几乎没有差异，但肥胖个体对 LPS 的皮质醇反应强烈减弱。较高的体脂百分比与较低的皮质醇对 LPS 的反应有关。总之，本研究中年轻和健康的肥胖人群并未表现出对细胞因子的行为敏感性增加，但皮质醇对免疫挑战的反应减弱。未来的研究将需要确定额外的生理和心理因素是否与肥胖状态相互作用以增加炎症引起的神经精神症状的风险。较高的体脂百分比与较低的皮质醇对 LPS 的反应有关。总之，本研究中年轻和健康的肥胖人群并未表现出对细胞因子的行为敏感性增加，但皮质醇对免疫挑战的反应减弱。未来的研究将需要确定额外的生理和心理因素是否与肥胖状态相互作用以增加炎症引起的神经精神症状的风险。较高的体脂百分比与较低的皮质醇对 LPS 的反应有关。总之，本研究中年轻和健康的肥胖人群并未表现出对细胞因子的行为敏感性增加，但皮质醇对免疫挑战的反应减弱。未来的研究将需要确定额外的生理和心理因素是否与肥胖状态相互作用以增加炎症引起的神经精神症状的风险。