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PMID: 18594791 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Increased fat:carbohydrate oxidation ratio in Il1ra (-/-) mice on a high-fat diet is associated with increased sympathetic tone.

Diabetologia ·Vol. 51 ·No. 9 ·2008-09-00 ·Pages 1698-706

Chida D, Hashimoto O, Kuwahara M, Sagara H, Osaka T, Tsubone H, Iwakura Y

Abstract

Proinflammatory cytokines, including IL-1, exert pleiotropic effects on the neuro-immuno-endocrine system. Previously, we showed that mice with knockout of the gene encoding IL-1 receptor antagonist (Il1ra (-/-), also known as Il1rn (-/-)) have a lean phenotype. The present study was designed to analyse the mechanisms leading to this lean phenotype. Il1ra (-/-) mice were fed a high-fat diet following weaning. Energy expenditure, body temperature, heart rate, blood parameters, urinary catecholamines and adipose tissue were analysed. Il1ra (-/-) mice exhibited resistance to obesity induced by a high-fat diet; this resistance was associated with increased energy expenditure and a decreased respiratory quotient, indicating that the ratio of fat:carbohydrate metabolism in Il1ra (-/-) mice is greater than in controls. Activity level in Il1ra (-/-) mice was significantly decreased and body temperature was significantly increased, compared with wild-type (WT) mice. Inguinal white adipose tissues in Il1ra (-/-) mice express increased levels of Ucp1 and mitochondrial respiratory chain genes compared with WT mice. Histological analysis of adipose tissue in Il1ra (-/-) mice revealed that brown adipose tissue is hyperactive and inguinal white adipose tissue contains smaller cells, which exhibit the distinctive multilocular appearance of brown adipocytes. Urinary epinephrine and norepinephrine excretion in Il1ra (-/-) mice was significantly increased compared with WT mice, suggesting that Il1ra (-/-) mice have increased sympathetic tone. Consistent with this, heart rate in Il1ra (-/-) mice was also significantly increased. Our results show that Il1ra (-/-) mice have increased energy expenditure, fat:carbohydrate oxidation ratio, body temperature, heart rate and catecholamine production. All of these observations are consistent with an enhanced sympathetic tone.

MeSH Terms
Adipose Tissue, Brown/pathology,physiopathology Animals Dietary Carbohydrates/metabolism Dietary Fats/metabolism Energy Metabolism Epinephrine/urine Inflammation/pathology,physiopathology Interleukin 1 Receptor Antagonist Protein/deficiency,genetics,metabolism Mice Mice, Knockout Norepinephrine/urine Sympathetic Nervous System/physiopathology
Chemicals
Dietary Carbohydrates Dietary Fats Il1rn protein, mouse Interleukin 1 Receptor Antagonist Protein Norepinephrine Epinephrine
Authors & Affiliations
7 authors, click to expand affiliations / ORCID
Chida D
Division of Cell Biology, Center for Experimental Medicine, Institute of Medical Science, University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639, Japan.
Hashimoto O
Kuwahara M
Sagara H
Osaka T
Tsubone H
Iwakura Y
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Article Info
Journal
Diabetologia
Abbr.
Diabetologia
ISSN
0012-186X
DOI
10.1007/s00125-008-1075-z
Published
2008-09-00
Epub
2008-00-02
Pages
1698-706
Language
English
Region
Germany
NLM ID
0006777
Subset
IM
External Links
PubMed source DOI: 10.1007/s00125-008-1075-z View journal details
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