肥胖与脂肪组织中的巨噬细胞积聚有关

Obesity is associated with macrophage accumulation in adipose tissue

 

文摘

肥胖会改变脂肪组织的代谢和内分泌功能，导致脂肪酸、激素和促炎分子的释放，导致肥胖相关的并发症。为了进一步描述脂肪组织中脂肪含量增加的变化，我们从肥胖相关的基因突变agouti (Ay)和肥胖(Lepob)中观察了肥胖组小鼠腹旁腺脂肪组织的转录表达。我们发现1,304份转录本的表达与体重显著相关。

　

　

 

在100个最显著相关的基因中，30%的编码蛋白是巨噬细胞的特征，与体重正相关。免疫组化分析发现，表达巨噬细胞标记物F4/80 (F4/80+)的细胞百分比与脂肪细胞大小和体重呈显著正相关。巨噬细胞抗原CD68的皮下脂肪组织中也发现了类似的关系。骨髓移植研究和巨噬细胞(Csf1op/op)小鼠脂肪组织中巨噬细胞数量的定量表明，这些F4/80+细胞是CSF-1依赖性的、骨髓来源的脂肪组织巨噬细胞。

 

表达分析巨噬细胞和非巨噬细胞细胞群从脂肪组织分离表明脂肪组织巨噬细胞负责几乎所有脂肪组织TNF-α 的表达和大量iNOS和IL- 6表达。脂肪组织巨噬细胞的数量在肥胖中增加，并参与炎症通路，这些通路在肥胖个体的脂肪组织中被激活。

　

 

Obesity is associated with macrophage accumulation in adipose tissue

Stuart P. Weisberg,1 Daniel McCann,1 Manisha Desai,2 Michael Rosenbaum,1 Rudolph L. Leibel,1,3,4 and Anthony W. Ferrante Jr.3,4

First published December 15, 2003 - More info

 

Abstract

Obesity alters adipose tissue metabolic and endocrine function and leads to an increased release of fatty acids, hormones, and proinflammatory molecules that contribute to obesity associated complications. To further characterize the changes that occur in adipose tissue with increasing adiposity, we profiled transcript expression in perigonadal adipose tissue from groups of mice in which adiposity varied due to sex, diet, and the obesity-related mutations agouti (Ay) and obese (Lepob). We found that the expression of 1,304 transcripts correlated significantly with body mass. Of the 100 most significantly correlated genes, 30% encoded proteins that are characteristic of macrophages and are positively correlated with body mass. Immunohistochemical analysis of perigonadal, perirenal, mesenteric, and subcutaneous adipose tissue revealed that the percentage of cells expressing the macrophage marker F4/80 (F4/80+) was significantly and positively correlated with both adipocyte size and body mass. Similar relationships were found in human subcutaneous adipose tissue stained for the macrophage antigen CD68. Bone marrow transplant studies and quantitation of macrophage number in adipose tissue from macrophage-deficient (Csf1op/op) mice suggest that these F4/80+ cells are CSF-1 dependent, bone marrow–derived adipose tissue macrophages. Expression analysis of macrophage and nonmacrophage cell populations isolated from adipose tissue demonstrates that adipose tissue macrophages are responsible for almost all adipose tissue TNF-α expression and significant amounts of iNOS and IL-6 expression. Adipose tissue macrophage numbers increase in obesity and participate in inflammatory pathways that are activated in adipose tissues of obese individuals.

JCI - Obesity is associated with macrophage accumulation in adipose tissue  https://www.jci.org/articles/view/19246