期刊
AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM
卷 310, 期 8, 页码 E676-E687出版社
AMER PHYSIOLOGICAL SOC
DOI: 10.1152/ajpendo.00028.2015
关键词
uncoupling protein 1; thermogenic adipocyte; inflammation; mitochondrial biogenesis; macrophage; tumor necrosis factor-alpha
资金
- Ministry of Education, Culture, Sports, Science, and Technology of Japan [22228001, 22380075, 24229, 24688015]
- Grants-in-Aid for Scientific Research [24688015] Funding Source: KAKEN
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.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据