Interleukin-18 null mutation increases weight and food intake and reduces energy expenditure and lipid substrate utilization in high-fat diet fed mice.
Interleukin-18 null mutation increases weight and food intake and reduces energy expenditure and lipid substrate utilization in high-fat diet fed mice.
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DOI：
10.1016/j.bbi.2013.12.001
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发表时间：
2014-03
影响因子：
15.1
通讯作者：
Conti, Bruno
中科院分区：
文献类型：
--
作者：
Zorrilla, Eric P.;Conti, Bruno
关键词：
促炎细胞因子白细胞介素 18 (IL-18) 可能调节食物摄入和能量代谢，但 IL-18 对高脂肪饮食喂养动物的影响尚不清楚。 IL-18 是否改变基础代谢率或生命代谢过程尚不清楚。在这里，我们测试了这样的假设：IL-18 调节高脂肪饮食喂养小鼠的体重增加、能量摄入、全身能量消耗以及脂质作为燃料底物的利用。将 IL-18 敲除小鼠的食物摄入量、全身代谢和运动活动与野生型同窝小鼠进行比较；比较了 IL-18 受体敲除小鼠、IL-18/IL-18R 敲除小鼠和野生型小鼠脑室内注射 IL-18 的食欲效果。饲料饲养的 IL-18 敲除小鼠在 6 个月大时体重超重，随后在低脂和高脂饮食中体重均增加，摄入更多高脂饮食，并表现出全身能量消耗减少和呼吸交换比增加。 IL-18 敲除小鼠的能量消耗在禁食与喂养条件、低脂肪饮食与高脂肪饮食、高水平与低水平的体力活动和一天中的时间中均有所减少，这表明对基础代谢率有影响。在 IL-18 敲除小鼠中，能量消耗的昼夜节律幅度也被减弱，但呼吸交换率、食物摄入或运动活动却没有减弱。中枢性 IL-18 给药可减少野生型小鼠的高脂肪饮食摄入量，但不会减少缺乏 IL-18 受体的小鼠的高脂肪饮食摄入量。功能丧失的结果支持这样的假设：内源性 IL-18 不仅在疾病期间而且在食用高脂肪饮食的健康成年人中都会抑制食欲并促进能量消耗和脂质燃料底物利用。
The proinflammatory cytokine interleukin-18 (IL-18) putatively modulates food intake and energy metabolism, but the effects of IL-18 in high-fat diet fed animals are unknown. Whether IL-18 alters basal metabolic rate or metabolic processes of living is unknown. Here, we tested the hypothesis that IL-18 modulates weight gain, energy intake, whole-body energy expenditure, and utilization of lipid as a fuel substrate in high-fat diet fed mice. Food intake, whole-body metabolism, and motor activity of IL-18 knockout mice were compared to those of wildtype littermates; anorectic effects of intracerebroventricular IL-18 administration were compared between IL-18 receptor knockout, IL-18/IL-18R knockout and wildtype mice. Chow-reared IL-18 knockout mice were overweight at 6 months of age and then gained excess weight on both low-fat and high-fat diets, ate more high-fat diet, and showed reduced whole-body energy expenditure and increased respiratory exchange ratios. Reductions in energy expenditure of IL-18 knockout mice were seen across fasting vs. feeding conditions, low- vs. high-fat diets, high vs. low levels of physical activity and times of day, suggesting actions on basal metabolic rate. The circadian amplitude of energy expenditure, but not respiratory exchange ratio, food intake, or motor activity, also was blunted in IL-18 knockout mice. Central IL-18 administration reduced high-fat diet intake in wildtype mice, but not in mice lacking the IL-18 receptor. The loss-of-function results support the hypothesis that endogenous IL-18 suppresses appetite and promote energy expenditure and lipid fuel substrate utilization not only during sickness, but also in healthy adults consuming high-fat diets.
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