| Autor: |
Menghuan Li, Yanting Hou, Yao Chen, Chaoyue Sun, Maodi Liang, Xiaolong Chu, Xin Wen, Fangyuan Yuan, Chaoling Peng, Cuizhe Wang, Jianxin Xie, Jun Zhang |
| Jazyk: |
angličtina |
| Rok vydání: |
2024 |
| Předmět: |
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| Zdroj: |
Nutrition & Diabetes, Vol 14, Iss 1, Pp 1-11 (2024) |
| Druh dokumentu: |
article |
| ISSN: |
2044-4052 |
| DOI: |
10.1038/s41387-024-00334-x |
| Popis: |
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. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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