期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 104, 期 26, 页码 11097-11102出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.0611523104
关键词
obesity; food intake; proinflammatory cytokine; body weight; overweight
资金
- NIA NIH HHS [R01 AG028040, AG28040] Funding Source: Medline
- NIDDK NIH HHS [R21 DK077616, DK077616, DK07118] Funding Source: Medline
- NINDS NIH HHS [NS43501, R01 NS043501] Funding Source: Medline
- PHS HHS [P30N5057096] Funding Source: Medline
Circulating levels of the cytokine interleukin 18 (IL-18) are elevated in obesity. Here, we show that administration of IL-18 suppresses appetite, feed efficiency, and weight regain in food-deprived male and female C57BL/6J mice. Intraperitoneal vs. intracerebroventricular routes of IL-18 administration had similar potency and did not promote formation of a conditioned taste aversion (malaise-like behavior). Mice partially (I/18(+/-)) or totally (I/18(-/-)) deficient in IL-18 were hyperphagic by young adulthood, with null mutants then becoming overweight by the fifth month of life. Adult I/18(-/-) mice gained 2- to 3-fold more weight than WT mice per unit energy consumed of low- or high-fat diet. Indirect calorimetry revealed reduced energy expenditure in female I/18(-/-) mice and increased respiratory exchange ratios [volume of carbon dioxide production (VCO2)/volume of oxygen consumption (VO2)] in mutants of both sexes. Hyperphagia continued in maturity, with overeating greatest during the mid- to late-dark cycle. Relative white fat-pad mass of I/18(-/-) mice was approximate to 2- to 3-fold greater than that of WT, with gonadal, mesenteric, and inguinal depots growing most. The data suggest that endogenous IL-18 signaling modulates food intake, metabolism, and adiposity during adulthood and might be a central or peripheral pharmacological target for controlling energy homeostasis.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据