PMID- 17578927
OWN - NLM
STAT- MEDLINE
DCOM- 20080115
LR  - 20231212
IS  - 1091-6490 (Electronic)
IS  - 0027-8424 (Print)
IS  - 0027-8424 (Linking)
VI  - 104
IP  - 26
DP  - 2007 Jun 26
TI  - Interleukin-18 controls energy homeostasis by suppressing appetite and feed 
      efficiency.
PG  - 11097-102
AB  - 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.
FAU - Zorrilla, Eric P
AU  - Zorrilla EP
AD  - Harold L. Dorris Neurological Research Institute, Committee on the Neurobiology 
      of Addictive Disorders, and Molecular and Integrative Neurosciences Department, 
      The Scripps Research Institute, La Jolla, CA 92037, USA. ezorrilla@scripps.edu
FAU - Sanchez-Alavez, Manuel
AU  - Sanchez-Alavez M
FAU - Sugama, Shuei
AU  - Sugama S
FAU - Brennan, Molly
AU  - Brennan M
FAU - Fernandez, Rosette
AU  - Fernandez R
FAU - Bartfai, Tamas
AU  - Bartfai T
FAU - Conti, Bruno
AU  - Conti B
LA  - eng
GR  - P30N5057096/PHS HHS/United States
GR  - AG28040/AG/NIA NIH HHS/United States
GR  - R21 DK077616/DK/NIDDK NIH HHS/United States
GR  - NS43501/NS/NINDS NIH HHS/United States
GR  - DK077616/DK/NIDDK NIH HHS/United States
GR  - R01 NS043501/NS/NINDS NIH HHS/United States
GR  - R01 AG028040/AG/NIA NIH HHS/United States
GR  - DK07118/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20070619
PL  - United States
TA  - Proc Natl Acad Sci U S A
JT  - Proceedings of the National Academy of Sciences of the United States of America
JID - 7505876
RN  - 0 (Appetite Depressants)
RN  - 0 (Interleukin-18)
SB  - IM
MH  - Adiposity/drug effects
MH  - Age Factors
MH  - Animals
MH  - Appetite/*drug effects
MH  - Appetite Depressants
MH  - Eating/*drug effects
MH  - Energy Intake/*drug effects
MH  - Female
MH  - Homeostasis
MH  - Interleukin-18/genetics/*pharmacology/*physiology
MH  - Male
MH  - Metabolism/drug effects
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Overweight
MH  - Pulmonary Gas Exchange
MH  - Sex Factors
PMC - PMC1904154
COIS- Conflict of interest statement: E.P.Z., B.C., M.S.-A., and T.B. have filed an 
      invention disclosure regarding the use of IL-18 and related molecules to control 
      energy homeostasis.
EDAT- 2007/06/21 09:00
MHDA- 2008/01/16 09:00
PMCR- 2007/12/26
CRDT- 2007/06/21 09:00
PHST- 2007/06/21 09:00 [pubmed]
PHST- 2008/01/16 09:00 [medline]
PHST- 2007/06/21 09:00 [entrez]
PHST- 2007/12/26 00:00 [pmc-release]
AID - 0611523104 [pii]
AID - 6835 [pii]
AID - 10.1073/pnas.0611523104 [doi]
PST - ppublish
SO  - Proc Natl Acad Sci U S A. 2007 Jun 26;104(26):11097-102. doi: 
      10.1073/pnas.0611523104. Epub 2007 Jun 19.