Obesity and Fatty Acids Promote Mitochondrial Translocation of STAT3 Through ROS-Dependent Mechanisms.
Obesity and Fatty Acids Promote Mitochondrial Translocation of STAT3 Through ROS-Dependent Mechanisms.
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肥胖和脂肪酸通过ros依赖机制促进STAT3的线粒体易位。
DOI：
10.3389/fragi.2022.924003
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发表时间：
2022
影响因子：
--
通讯作者：
Bharath, Leena P.
中科院分区：
文献类型：
--
作者：
Conway, Rachel;Rockhold, Jack Donato;SantaCruz-Calvo, Sara;Zukowski, Emelia;Pugh, Gabriella H.;Hasturk, Hatice;Kern, Philip A.;Nikolajczyk, Barbara S.;Bharath, Leena P.
肥胖促进代谢和炎症性疾病如2型糖尿病的发生和发展。肥胖期间发生的慢性低度炎症触发了多种信号传导机制，对生物体健康产生负面影响。一种这样的机制是STAT 3的持续激活和线粒体易位，其涉及炎症病理学和许多类型的癌症。线粒体中的STAT 3（mitoSTAT 3）改变电子传递链活性，从而影响营养代谢和免疫应答。肥胖但糖耐量正常（NGT）的中年受试者的PBMC和CD 4 + T细胞比瘦受试者的细胞具有更高的STAT 3在残基丝氨酸727上的磷酸化和更多的STAT 3的线粒体积累。为了评估肥胖症中的循环脂质过量是否是年龄和性别匹配的mitoSTAT 3的原因，分别用生理相关剂量的饱和和单不饱和脂肪酸棕榈酸酯和油酸酯攻击来自瘦受试者的细胞。脂肪酸处理导致所有细胞类型中mitoSTAT 3的大量积累，这与棕榈酸诱导的自噬损伤无关。用脂肪酸和海藻糖共同处理细胞可以防止STAT 3磷酸化和线粒体积累，这是一种不依赖于自噬但依赖于细胞过氧化物的机制。通过靶向STAT 3抑制剂或ROS清除对mitoSTAT 3的药理学阻断防止肥胖和脂肪酸诱导的促炎细胞因子IL-17 A和IL-6的产生，从而建立mitoSTAT 3和炎性细胞因子产生之间的机制联系。
Obesity promotes the onset and progression of metabolic and inflammatory diseases such as type 2 diabetes. The chronic low-grade inflammation that occurs during obesity triggers multiple signaling mechanisms that negatively affect organismal health. One such mechanism is the persistent activation and mitochondrial translocation of STAT3, which is implicated in inflammatory pathologies and many types of cancers. STAT3 in the mitochondria (mitoSTAT3) alters electron transport chain activity, thereby influencing nutrient metabolism and immune response. PBMCs and CD4+ T cells from obese but normal glucose-tolerant (NGT) middle-aged subjects had higher phosphorylation of STAT3 on residue serine 727 and more mitochondrial accumulation of STAT3 than cells from lean subjects. To evaluate if circulating lipid overabundance in obesity is responsible for age- and sex-matched mitoSTAT3, cells from lean subjects were challenged with physiologically relevant doses of the saturated and monounsaturated fatty acids, palmitate and oleate, respectively. Fatty acid treatment caused robust accumulation of mitoSTAT3 in all cell types, which was independent of palmitate-induced impairments in autophagy. Co-treatment of cells with fatty acid and trehalose prevented STAT3 phosphorylation and mitochondrial accumulation in an autophagy-independent but cellular peroxide–dependent mechanism. Pharmacological blockade of mitoSTAT3 either by a mitochondria-targeted STAT3 inhibitor or ROS scavenging prevented obesity and fatty acid–induced production of proinflammatory cytokines IL-17A and IL-6, thus establishing a mechanistic link between mitoSTAT3 and inflammatory cytokine production.
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中枢瘦素抵抗中的 STAT3 磷酸化
影响因子：
4.5
作者：
Liu H;Du T;Li C;Yang G
通讯作者：
Yang G
影响因子：
5.6
作者：
Rincon M;Pereira FV
通讯作者：
Pereira FV
DOI：
10.1126/science.1164551
发表时间：
2009-02-06
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
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Larner AC
影响因子：
3.7
作者：
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通讯作者：
Levy DE
影响因子：
9
作者：
Ploeger C;Huth T;Sugiyanto RN;Pusch S;Goeppert B;Singer S;Tabti R;Hausser I;Schirmacher P;Désaubry L;Roessler S
通讯作者：
Roessler S