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

被引：15

作者：

Chida, D. ^{[1
,2
]}

Hashimoto, O. ^{[1
]}

Kuwahara, M. ^{[3
]}

Sagara, H. ^{[4
]}

Osaka, T. ^{[5
]}

Tsubone, H. ^{[3
]}

Iwakura, Y. ^{[1
]}

机构：

[1] Univ Tokyo, Inst Med Sci, Ctr Med Expt, Div Cell Biol,Minato Ku, Tokyo 1088639, Japan

[2] Int Med Ctr Japan, Res Inst, Dept Pathol, Tokyo, Japan

[3] Univ Tokyo, Dept Comparat Pathophysiol, Grad Sch Agr & Life Sci, Tokyo 1088639, Japan

[4] Univ Tokyo, Inst Med Sci, Dept Basic Med Sci, Fine Morphol Lab, Tokyo 1088639, Japan

[5] Natl Inst Hlth & Nutr, Tokyo 162, Japan

来源：

DIABETOLOGIA | 2008年 / 51卷 / 09期

关键词：

brown adipose tissue; IL-1; proinflammatory cytokines; sympathetic tone; white adipose tissue;

D O I：

10.1007/s00125-008-1075-z

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

Aims/hypothesis 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. Methods 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. Results 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. Conclusions/interpretation 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.

引用

页码：1698 / 1706

页数：9

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