Obesity and the risk of Multiple Sclerosis. The role of Leptin.
Obesity and the risk of Multiple Sclerosis. The role of Leptin.
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肥胖与多发性硬化症的风险。Leptin的作用
DOI：
10.1002/acn3.51291
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发表时间：
2021-03
影响因子：
5.3
通讯作者：
Correale J
中科院分区：
文献类型：
--
作者：
Marrodan M;Farez MF;Balbuena Aguirre ME;Correale J
研究瘦素对不同T细胞群的影响，以更深入地了解瘦素与肥胖之间的联系。309名RRMS患者和322名对照参与了一项横断面调查，以确认青春期或成年早期的超重/肥胖是否会增加MS的风险。从外周血单核细胞扩增MBP 83 -102和MOG 63 -87肽特异性T细胞系。通过RT-PCR和流式细胞术测量瘦素受体表达。采用ELISA法检测Bcl-2、p-STAT 3、pERK 1/2和p27 kip 1的表达，并通过Annexin V检测确定凋亡诱导。通过ELISPOT和ELISA评估细胞因子，并通过流式细胞术评估调节性T细胞（TCFs）。Logistic回归分析显示，15岁超重和20岁肥胖增加MS风险（OR = 2.16，P = 0.01和OR = 3.9，P = 0.01）。两组的瘦素水平均与BMI相关。瘦素的添加增加了自身反应性T细胞增殖，减少了凋亡诱导，并促进了促炎细胞因子分泌。与超重/正常/体重不足受试者相比，肥胖患者产生更多的促炎细胞因子。瘦素水平与循环Treg细胞呈负相关（r =-0.97，P < 0.0001）。瘦素抑制Treg增殖。瘦素对CD 4 + CD 25 −效应T细胞的影响是通过增加STAT 3和ERK 1/2磷酸化以及下调细胞周期抑制剂P27 kip 1介导的。与此相反，瘦素对TGFAP的影响是由于ERK 1/2磷酸化水平降低和p27 kip 1上调。瘦素促进自身反应性T细胞增殖和促炎细胞因子分泌，但抑制Treg细胞增殖。
To investigate the effects of leptin on different T‐cell populations, in order to gain more insight into the link between leptin and obesity. Three hundred and nine RRMS patients and 322 controls participated in a cross‐sectional survey, to confirm whether excess weight/obesity in adolescence or early adulthood increased the risk of MS. Serum leptin levels were determined by ELISA. MBP83–102, and MOG63–87 peptide‐specific T cells lines were expanded from peripheral blood mononuclear cells. Leptin receptor expression was measured by RT‐PCR and flow cytometry. Bcl‐2, p‐STAT3, pERK1/2, and p27kip1 expression were assayed using ELISA, and apoptosis induction was determined by Annexin V detection. Cytokines were assessed by ELISPOT and ELISA, and regulatory T cells (Tregs) by flow cytometry. Logistic regression analysis, showed excess weight at age 15, and obesity at 20 years of age increased MS risk (OR = 2.16, P = 0.01 and OR = 3.9, P = 0.01). Leptin levels correlated with BMI in both groups. The addition of Leptin increased autoreactive T‐cell proliferation, reduced apoptosis induction, and promoted proinflammatory cytokine secretion. Obese patients produced more proinflammatory cytokines compared to overweight/normal/underweight subjects. Inverse correlation was found between leptin levels and circulating Treg cells (r = −0.97, P < 0.0001). Leptin inhibited Treg proliferation. Effects of leptin on CD4+CD25− effector T cells were mediated by increased STAT3 and ERK1/2 phosphorylation, and down modulation of the cell cycle inhibitor P27kip1. In contrast, leptin effects on Tregs resulted from decreased phosphorylation of ERK1/2 and upregulation of p27kip1. Leptin promotes autoreactive T‐cell proliferation and proinflammatory cytokine secretion, but inhibits Treg‐cell proliferation.
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DOI：
10.1530/joe-13-0339
发表时间：
2014-02
期刊：
The Journal of endocrinology
影响因子：
--
作者：
Cao H
通讯作者：
Cao H
影响因子：
8
作者：
Kawada, M;Yamagoe, S;Uehara, Y
通讯作者：
Uehara, Y
影响因子：
5.3
作者：
Kerkhoff, E;Rapp, UR
通讯作者：
Rapp, UR
影响因子：
4.6
作者：
Fernandez-Riejos, P.;Goberna, R.;Sanchez-Margalet, V.
通讯作者：
Sanchez-Margalet, V.
影响因子：
32.4
作者：
De Rosa, Veronica;Procaccini, Claudio;Matarese, Giuseppe
通讯作者：
Matarese, Giuseppe