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Interleukin-18 controls energy homeostasis by suppressing appetite and feed efficiency

Author:
Zorrilla, Eric P., Sanchez-Alavez, Manuel, Sugama, Shuei, Brennan, Molly, Fernandez, Rosette, Bartfai, Tamas, Conti, Bruno
Source:
Proceedings of the National Academy of Sciences of the United States of America 2007 v.104 no.26 pp. 11097-11102
ISSN:
0027-8424
Subject:
low fat diet, weight gain, carbon dioxide, high fat diet, interleukins, food conversion, energy metabolism, appetite, gas exchange, energy expenditure, oxygen consumption, overweight, mice, overeating, homeostasis, breathing, body fat
Abstract:
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 (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 Il18⁻/⁻ mice was [almost equal 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.
Agid:
2353104