| First Author | Zorrilla EP | Year | 2007 |
| Journal | Proc Natl Acad Sci U S A | Volume | 104 |
| Issue | 26 | Pages | 11097-102 |
| PubMed ID | 17578927 | Mgi Jnum | J:122588 |
| Mgi Id | MGI:3714707 | Doi | 10.1073/pnas.0611523104 |
| Citation | Zorrilla EP, et al. (2007) Interleukin-18 controls energy homeostasis by suppressing appetite and feed efficiency. Proc Natl Acad Sci U S A 104(26):11097-102 |
| abstractText | 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 (Il18(+/-)) or totally (Il18(-/-)) deficient in IL-18 were hyperphagic by young adulthood, with null mutants then becoming overweight by the fifth month of life. Adult Il18(-/-) 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 Il18(-/-) mice and increased respiratory exchange ratios [volume of carbon dioxide production (VCO(2))/volume of oxygen consumption (VO(2))] 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 Il18(-/-) mice was approximately 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. |
