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

Nutrition & Metabolism

Yuchun Deng¹  Tongtong Qiu¹  Xin Yang¹  Jianxin Xie¹  Jun Zhang¹  Cuizhe Wang¹  Jingzhou Wang¹  Xiaolong Chu¹  Jiaojiao Zhu¹  Chongge Pan¹  Jianyu Xiong¹  Yongsheng Chang² 

[1]Medical College of Shihezi University, Bei-Er-Lu, 832000, Shihezi, Xinjiang, China

[2]Medical College of Shihezi University, Bei-Er-Lu, 832000, Shihezi, Xinjiang, China

[3]Department of Physiology and Pathophysiology, Tianjin Medical University, 300000, Tianjin, China

关键词: Obesity;    Palmitic acid;    Oleic acid;    Adipocyte;    KLF15;   

DOI  :  10.1186/s12986-021-00628-2

来源: Springer

【 摘 要 】

BackgroundObesity-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.MethodsLevels 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.ResultsKLF15 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.ConclusionsBoth 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.

【 授权许可】

CC BY