PA and OA induce abnormal glucose metabolism by inhibiting KLF15 in adipocytes.
PA and OA induce abnormal glucose metabolism by inhibiting KLF15 in adipocytes.
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PA和OA通过抑制脂肪细胞中的KLF15诱导糖代谢异常
DOI：
10.1186/s12986-021-00628-2
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发表时间：
2021-11-21
影响因子：
4.5
通讯作者：
Zhang J
中科院分区：
文献类型：
--
作者：
Wang C;Chu X;Deng Y;Wang J;Qiu T;Zhu J;Yang X;Pan C;Xiong J;Xie J;Chang Y;Zhang J
肥胖引起的血清游离脂肪酸（FFA）水平升高导致2型糖尿病（T2DM）的发生。然而，分子机制在很大程度上仍然是个谜。本研究旨在探讨KLF15对FFAs诱导的糖代谢异常的影响及机制。通过不同的检测试剂盒测量 TG、TC、HDL-C、LDL-C 和葡萄糖水平。采用qRT-PCR和Western Blot检测GPR120、GPR40、p38 MAPK、KLF15及下游因子的磷酸化水平。肥胖受试者和高脂饮食 (HFD) 小鼠的内脏脂肪组织中 KLF15 降低。在HFD小鼠中，GPR120拮抗剂显着促进KLF15蛋白表达水平和p38 MAPK磷酸化，同时降低血糖水平。同时，阻断 GPR40 会抑制 KLF15 的表达。在3T3-L1脂肪细胞中，1500 μM PA通过GPR120/P-p38 MAPK信号通路抑制KLF15，750 μM OA主要通过GPR120而不依赖于P-p38 MAPK抑制KLF15，最终导致糖代谢异常。不幸的是，GPR40 对 PA 或 OA 诱导的 KLF15 减少没有贡献。 PA和OA均通过GPR120抑制KLF15表达，导致脂肪细胞糖代谢异常。值得注意的是，PA 对 KLF15 表达的抑制取决于 p38 MAPK 的磷酸化。在线版本包含可在 10.1186/s12986-021-00628-2 获取的补充材料。
Obesity-induced elevated serum free fatty acids (FFAs) levels result in the occurrence of type 2 diabetes mellitus (T2DM). However, the molecular mechanism remains largely enigmatic. This study was to explore the effect and mechanism of KLF15 on FFAs-induced abnormal glucose metabolism. Levels of TG, TC, HDL-C, LDL-C, and glucose were measured by different assay kits. qRT-PCR and Western Blot were used to detect the levels of GPR120, GPR40, phosphorylation of p38 MAPK, KLF15, and downstream factors. KLF15 was decreased in visceral adipose tissue of obesity subjects and high-fat diet (HFD) mice. In HFD mice, GPR120 antagonist significantly promoted KLF15 protein expression level and phosphorylation of p38 MAPK, meanwhile reduced the blood glucose levels. While, blocking GPR40 inhibited the KLF15 expression. In 3T3-L1 adipocytes, 1500 μM PA inhibited KLF15 through a GPR120/P-p38 MAPK signal pathway, and 750 μM OA inhibited KLF15 mainly through GPR120 while not dependent on P-p38 MAPK, ultimately resulting in abnormal glucose metabolism. Unfortunately, GPR40 didn’t contribute to PA or OA-induced KLF15 reduction. Both PA and OA inhibit KLF15 expression through GPR120, leading to abnormal glucose metabolism in adipocytes. Notably, the inhibition of KLF15 expression by PA depends on phosphorylation of p38 MAPK. The online version contains supplementary material available at 10.1186/s12986-021-00628-2.
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影响因子：
3.7
作者：
Enomoto T;Ohashi K;Shibata R;Kambara T;Uemura Y;Yuasa D;Kataoka Y;Miyabe M;Matsuo K;Joki Y;Hayakawa S;Hiramatsu-Ito M;Ito M;Murohara T;Ouchi N
通讯作者：
Ouchi N
影响因子：
29
作者：
Steneberg, R;Rubins, N;Edlund, H
通讯作者：
Edlund, H
影响因子：
4.8
作者：
Suckow, Arthur T.;Polidori, David;Briscoe, Celia P.
通讯作者：
Briscoe, Celia P.
影响因子：
3.4
作者：
Liu B;Xu L;Yu X;Li W;Sun X;Xiao S;Guo M;Wang H
通讯作者：
Wang H
影响因子：
7.2
作者：
Muscara, Claudia;Molonia, Maria Sofia;Cristani, Mariateresa
通讯作者：
Cristani, Mariateresa