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.

The role of free fatty acid receptor-1 in gastric contractions in Suncus murinus

“…25 In order to observe the effect of OA through FFAR1, suncus was IP injected with the FFAR1 antagonist (GW1100) (2.5 mg kg −1 ) within 5 min of the onset of phase I contractions, followed by the administration of OA (160 mg kg −1 , IG) 15 min later. 26 The same suncus received an injection of the same quantity of 2.5% DMSO/saline as a vehicle.…”

Distribution and Functional Significance of KLF15 in Mouse Cerebellum

“…Kruppel-like factor (KLF) is a transcription factor family with three highly conserved zinc nger structures that can bind to GC and CACCC sequences in the target gene promoters to exert their effects [20,21]. KLF15, one of KLF family members, is widely distributed in many tissues [22,23], participate in the body's metabolism, tumors, immunity, and development [20,24,25].…”