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PA and OA induce abnormal glucose metabolism by inhibiting KLF15 in adipocytes.


ABSTRACT:

Background

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.

Methods

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.

Results

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.

Conclusions

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.

SUBMITTER: Wang C 

PROVIDER: S-EPMC8607635 | biostudies-literature | 2021 Nov

REPOSITORIES: biostudies-literature

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Publications

PA and OA induce abnormal glucose metabolism by inhibiting KLF15 in adipocytes.

Wang Cuizhe C   Chu Xiaolong X   Deng Yuchun Y   Wang Jingzhou J   Qiu Tongtong T   Zhu Jiaojiao J   Yang Xin X   Pan Chongge C   Xiong Jianyu J   Xie Jianxin J   Chang Yongsheng Y   Zhang Jun J  

Nutrition & metabolism 20211121 1


<h4>Background</h4>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.<h4>Methods</h4>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 p3  ...[more]

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