MiR-142-3p inhibits adipogenic differentiation and autophagy in obesity through targeting KLF9

MiR-142-3p has been shown to be suppressed in obese patients, while the underlying regulatory mechanism is unclear.

Body shape indexes as well as peripheral blood for biochemical parameter analysis were obtained from obese and healthy subjects. When 3T3-L1 cells were induced to differentiate, miR-142-3p expression was detected by quantitative real-time polymerase chain reaction (qRT-PCR). The effects of miR-142-3p on triglyceride (TG) and adipogenic differentiation-related genes during the adipogenic differentiation of 3T3-L1 cells were detected by transfection, Oil Red O staining, and Western blot. The targeting relationship between miR-142-3p and Krueppel-like transcription factor 9 (KLF9) was verified by TargetScan and dual-luciferase experiment. The specific regulatory effects of miR-142-3p on cell adipogenic differentiation and autophagy were analyzed by rescue experiments. In vivo experiments further validated the results of in vitro experiments through obese mouse models.

Obesity-marked biochemical indicators increased whereas high density lipoprotein and miR-142-3p decreased in obese patients. The content of miR-142-3p gradually decreased with cell lipid differentiation. Overexpression of miR-142-3p reduced TG deposition in cells by down-regulating lipid formation and fatty acid synthesis genes and up-regulating fatty acid oxidation genes. KLF9 targeting miR-142-3p was suppressed by miR-142-3p. KLF9 overexpression partially reversed the inhibitory effect of miR-142-3p mimic on adipogenic differentiation and the expressions of autophagy related-genes in 3T3-L1 cells. MiR-142-3p overexpression also inhibited fat cell differentiation and autophagy in obese mice.

Overexpressed miR-142-3p inhibited adipogenic differentiation and autophagy through targeting KLF9.