2016年4月
Macrophage infiltration into obese adipose tissues suppresses the induction of UCP1 level in mice
AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM
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- 巻
- 310
- 号
- 8
- 開始ページ
- E676
- 終了ページ
- E687
- 記述言語
- 英語
- 掲載種別
- 研究論文(学術雑誌)
- DOI
- 10.1152/ajpendo.00028.2015
- 出版者・発行元
- AMER PHYSIOLOGICAL SOC
Emergence of thermogenic adipocytes such as brown and beige adipocytes is critical for whole body energy metabolism. Promoting the emergence of these adipocytes, which increase energy expenditure, could be a viable strategy in treating obesity and its related diseases. However, little is known regarding the mechanisms that regulate the emergence of these adipocytes in obese adipose tissue. Here, we demonstrated that classically activated macrophages (M1 M phi) suppress the induction of thermogenic adipocytes in obese adipose tissues of mice. Cold exposure significantly induced the expression levels of uncoupling protein-1 (UCP1), which is a mitochondrial protein unique in thermogenic adipocytes, in C57BL/6 mice fed a normal diet. However, UCP1 induction was significantly suppressed in adipose tissues of C57BL/6 mice fed a high-fat diet, into which M1 M phi infiltrated. Depletion of M1 M phi using clodronate liposomes eliminated the suppressive effect and markedly reduced the mRNA level of tumor necrosis factor-alpha (TNF alpha) in the adipose tissues. Importantly, consistent with the observed changes in the expression levels of marker genes for thermogenic adipocytes, combination treatment of clodronate liposome and cold exposure resulted in metabolic benefits such as lowered body weight and blood glucose level in obese mice. Moreover, intraperitoneal injection of recombinant TNF alpha protein suppressed UCP1 induction in lean adipose tissues of mice. Collectively, our data indicate that infiltrated M1 M phi suppress the induction of thermogenic adipocytes in obese adipose tissues via TNF alpha. This report suggests that inflammation induced by infiltrated M phi could cause not only insulin resistance but also reduction of energy expenditure in adipose tissues.
- リンク情報
- ID情報
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- DOI : 10.1152/ajpendo.00028.2015
- ISSN : 0193-1849
- eISSN : 1522-1555
- PubMed ID : 26884382
- Web of Science ID : WOS:000374099100009