Affiliation:
1. The First Department of Cardiovascular, First Affiliated Hospital Heilongjiang University of Chinese Medicine Xiangfang District Harbin China
2. Experimental Training Center Heilongjiang University of Chinese Medicine Xiangfang District Harbin China
3. Heilongjiang University of Chinese Medicine Xiangfang District Harbin China
Abstract
AbstractObesity is a metabolic disease with excess weight. LncRNA SNHG14 is abnormally expressed in numerous diseases. This research aimed to enucleate the lncRNA SNHG14 role in obesity. Adipocytes were treated with free fatty acid (FFA) to establish an in vitro model for obesity. Mice were fed a high‐fat diet to construct an in vivo model. Gene levels were determined using quantitative real‐time PCR (RT‐PCR). The protein level was checked by western blot. The lncRNA SNHG14 role in obesity was assessed using western blot and enzyme‐linked immunosorbent assay. The mechanism was estimated by Starbase, dual‐luciferase reporter gene assay, and RNA pull‐down. LncRNA SNHG14 function in obesity was estimated using mouse xenograft models, RT‐PCR, western blot, and enzyme‐linked immunosorbent assay. LncRNA SNHG14 and BACE1 levels were increased, but the miR‐497a‐5p level was decreased in FFA‐induced adipocytes. Interference with lncRNA SNHG14 reduced endoplasmic reticulum (ER) stress‐related molecules GRP78 and CHOP expressions in FFA‐induced adipocytes, and decreased IL‐1β, IL‐6, and TNF‐α expressions, indicating that lncRNA SNHG14 knockdown mitigated FFA‐induced ER stress and inflammation in adipocytes. Mechanistically, lncRNA SNHG14 combined with miR‐497a‐5p, and miR‐497a‐5p targeted BACE1. Meanwhile, lncRNA SNHG14 knockdown reduced levels of GRP78, CHOP, IL‐1β, IL‐6, and TNF‐α, while cotransfection with anti‐miR‐497a‐5p or pcDNA‐BACE1 abolished these trends. Rescue assays illustrated that lncRNA SNHG14 knockdown relieved FFA‐induced adipocyte ER stress and inflammation through miR‐497a‐5p/BACE1. Meanwhile, lncRNA SNHG14 knockdown restrained adipose inflammation and ER stress caused by obesity in vivo. LncRNA SNHG14 mediated obesity‐induced adipose inflammation and ER stress through miR‐497a‐5p/BACE1.
Funder
National Natural Science Foundation of China
Subject
Health, Toxicology and Mutagenesis,Toxicology,Molecular Biology,Molecular Medicine,Biochemistry,General Medicine