Palmitic acid promotes miRNA release from adipocyte exosomes by activating NF-κB/ER stress

IF 4.6 2区 医学 Q1 ENDOCRINOLOGY & METABOLISM
Menghuan Li, Yanting Hou, Yao Chen, Chaoyue Sun, Maodi Liang, Xiaolong Chu, Xin Wen, Fangyuan Yuan, Chaoling Peng, Cuizhe Wang, Jianxin Xie, Jun Zhang
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引用次数: 0

Abstract

Objective

The release of adipose tissue-derived miRNAs is increased under conditions of obesity, but the exact molecular mechanisms involved have not been elucidated. This study investigated whether obesity-induced increases in palmitic acid (PA) content could activate the NF-κB/endoplasmic reticulum stress (ER stress) pathway and promote the expression and release of exosomal miRNAs in adipocytes.

Methods

Abdominal adipose tissue and serum samples were collected from normal weight individuals and people with obesity to clarify the correlation of serum PA content with NF-κB/ER stress and the release of exosomal miRNAs. NF-κB and ER stress were blocked in obese mice and in vitro cultured adipocytes to demonstrate the molecular mechanisms by which PA promotes the release of exosomal miRNAs.The morphology, particle size and distribution of the exosomes were observed via transmission electron microscopy and NTA.

Results

Accompanied by increased serum PA levels, the NF-κB/ER stress pathway was activated in the adipose tissue of people with obesity and in high-fat diet (HFD)-induced obese mice; moreover, the levels of miRNAs in both adipose tissue and serum were increased. P-p65 (Bay11-7082) and ER stress (TUDCA) blockers significantly reduced the levels of miRNAs in abdominal adipose tissue and serum, decreased blood glucose levels, and improved glucose tolerance and insulin sensitivity in obese mice. In 3T3-L1 adipocytes, high concentrations of PA activated the NF-κB/ER stress pathway and increased the expression and release of miRNAs in exosomes. P-p65 (Bay11-7082) and ER stress (TUDCA) blockers significantly reversed the increased release exosomal miRNAs cause by PA.

Conclusions

Obesity-induced increases in PA content increase the expression and release of miRNAs in adipocyte exosomes by activating the NF-κB/ER stress pathway.

Abstract Image

棕榈酸通过激活 NF-κB/ER 应激促进脂肪细胞外泌体释放 miRNA
目的肥胖会增加脂肪组织衍生 miRNA 的释放,但其确切的分子机制尚未阐明。方法收集正常体重者和肥胖者的腹部脂肪组织和血清样本,以明确血清中 PA 含量与 NF-κB/ER 应激和外泌体 miRNAs 释放的相关性。通过透射电子显微镜和 NTA 观察了外泌体的形态、粒径和分布。结果伴随着血清中PA水平的升高,肥胖症患者的脂肪组织和高脂饮食(HFD)诱导的肥胖小鼠的NF-κB/ER应激通路被激活;此外,脂肪组织和血清中的miRNA水平均升高。P-p65(Bay11-7082)和ER应激(TUDCA)阻断剂能显著降低腹部脂肪组织和血清中的miRNA水平,降低血糖水平,并改善肥胖小鼠的糖耐量和胰岛素敏感性。在 3T3-L1 脂肪细胞中,高浓度 PA 激活了 NF-κB/ER 应激途径,增加了外泌体中 miRNA 的表达和释放。结论肥胖引起的 PA 含量增加会激活 NF-κB/ER 应激途径,从而增加脂肪细胞外泌体中 miRNA 的表达和释放。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Nutrition & Diabetes
Nutrition & Diabetes ENDOCRINOLOGY & METABOLISM-NUTRITION & DIETETICS
CiteScore
9.20
自引率
0.00%
发文量
50
审稿时长
>12 weeks
期刊介绍: Nutrition & Diabetes is a peer-reviewed, online, open access journal bringing to the fore outstanding research in the areas of nutrition and chronic disease, including diabetes, from the molecular to the population level.
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