Sex Differences in Macrophage Responses to Obesity-Mediated Changes Determine Migratory and Inflammatory Traits.
Sex Differences in Macrophage Responses to Obesity-Mediated Changes Determine Migratory and Inflammatory Traits.
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DOI：
10.4049/jimmunol.2000490
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发表时间：
2021-01-01
期刊：
影响因子：
--
通讯作者：
Coss D
中科院分区：
文献类型：
--
作者：
Chen KE;Lainez NM;Coss D
肥胖对男性和女性影响不同的机制尚不清楚。由于巨噬细胞在功能上是肥胖诱导的炎症中最重要的细胞，我们试图确定巨噬细胞迁移中男性特异性倾向的原因。鉴于我们先前确定，雄性小鼠喂食高脂饮食（HFD）表现出巨噬细胞浸润到下丘脑，而女性受到保护，无论卵巢雌激素，在这里，我们表明，男性积累更多的巨噬细胞在脂肪组织，也是更多的炎症。使用骨髓细胞或巨噬细胞，在体外分化，从雄性和雌性小鼠喂食对照和HFD，我们证明，来自雄性小鼠的巨噬细胞本质上更具迁移性。我们确定男性血清和脂肪组织中的瘦素水平较高。然而，血清CCL2水平在雄性和雌性中是相同的，尽管与两种性别的瘦小鼠相比，肥胖小鼠中的CCL2水平增加。瘦素受体和游离脂肪酸受体，GPR120，只在来自雄性小鼠的巨噬细胞中上调，当培养在游离脂肪酸（FFA）的存在下，以模拟肥胖的高脂血症。除非预先用LPS刺激，否则CCL 2不会引起巨噬细胞的迁移。然而，瘦素引起两种性别的巨噬细胞迁移。雄性小鼠的巨噬细胞在与FFA培养时保持迁移能力，而雌性巨噬细胞则不能迁移。因此，高脂血症和高瘦素血症都有助于雄性巨噬细胞特异性迁移，因为FFA增加诱导瘦素受体，而更高的瘦素导致迁移。我们的研究结果可能解释了巨噬细胞浸润引起的肥胖介导的疾病的性别差异。
The mechanisms whereby obesity differentially affects males and females are unclear. Since macrophages are functionally the most important cells in obesity-induced inflammation, we sought to determine reasons for male-specific propensity in macrophage migration. Whereas we previously determined that male mice fed high fat diet (HFD) exhibit macrophage infiltration into the hypothalamus, while females were protected irrespective of ovarian estrogen, here we show that males accumulate more macrophages in adipose tissues that are also more inflammatory. Using bone marrow cells or macrophages, differentiated in vitro, from male and female mice fed control and HFD, we demonstrated that macrophages derived from male mice are intrinsically more migratory. We determined that males have higher levels of leptin in serum and adipose tissue. Serum CCL2 levels, however, are the same in males and females, although increased in obese mice compared to lean mice of both sexes. Leptin receptor and free fatty acid receptor, GPR120, are upregulated only in macrophages derived from male mice, when cultured in the presence of free fatty acids (FFA) to mimic hyperlipidemia of obesity. Unless previously stimulated with LPS, CCL2 did not cause migration of macrophages. Leptin, however, elicited migration of macrophages from both sexes. Macrophages from male mice maintained migratory capacity when cultured with FFA, while female macrophages failed to migrate. Therefore, both hyperlipidemia and hyperleptinemia contribute to male macrophage specific migration, since increased FFA induce leptin receptors, while higher leptin causes migration. Our results may explain sex differences in obesity-mediated disorders caused by macrophages infiltration.
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影响因子：
5.5
作者：
Gruen, Marnie L.;Hao, Mingming;Hasty, Alyssa H.
通讯作者：
Hasty, Alyssa H.
影响因子：
4.9
作者：
Grove, K. L.;Fried, S. K.;Greenberg, A. S.;Xiao, X. Q.;Clegg, D. J.
通讯作者：
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影响因子：
5.5
作者：
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通讯作者：
Shulman, Gerald, I
DOI：
10.1038/nri3071
发表时间：
2011-10-10
期刊：
Nature reviews. Immunology
影响因子：
--
作者：
通讯作者：
--
影响因子：
64.8
作者：
Baggiolini, M
通讯作者：
Baggiolini, M