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肥胖条件下脂肪组织来源的外泌体在骨骼肌和肝细胞中的作用:共性和差异。

Role of Exosomes Derived from Adipose Tissue under Obese Conditions in Skeletal Muscle and Liver Cells: Commonalities and Differences.

机构信息

Division of Food and Nutrition, Chonnam National University, Gwangju, 61186, Republic of Korea.

Human Ecology Research Institute, Chonnam National University, Gwangju, 61186, Republic of Korea.

出版信息

Mol Nutr Food Res. 2022 Dec;66(23):e2200358. doi: 10.1002/mnfr.202200358. Epub 2022 Sep 28.

Abstract

SCOPE

To determine the correlation between obesity and insulin resistance in skeletal muscle and liver tissues, this study isolates exosomes from adipose tissue under obese conditions and investigates the effect of adipose tissue-derived exosomes (Ad-exosomes) in mouse muscle (C2C12 cells) and liver cell lines (AML12 cells).

METHODS AND RESULTS

The study isolates exosomes from the adipose tissue of normal diet-fed mice or high-fat diet (HFD)-fed obese mice and confirms the uptake into differentiated C2C12 and AML12 cells. Ad-exosomes from HFD-fed mice induce insulin resistance, triglyceride (TG) accumulation, endoplasmic reticulum stress, and inflammation in both C2C12 and AML12 cells. Interestingly, the study finds that the TG accumulation induces by Ad-exosomes from HFD-fed obese mice is dramatically increased in AML12 cells compared with that in the differentiated C2C12 cells, and glucose uptake following the same treatment is decreased in C2C12 cells and increased in AML12 cells. In addition, Ad-exosomes from HFD-fed obese mice cause not only TG accumulation but also lipogenesis in AML12 cells.

CONCLUSIONS

The results suggest that Ad-exosomes from HFD-fed obese mice cause insulin resistance in both the muscles and liver, but their effects on metabolism during the development of insulin resistance vary between tissues.

摘要

目的

为了确定肥胖症与骨骼肌和肝组织胰岛素抵抗之间的相关性,本研究从肥胖条件下的脂肪组织中分离出外泌体,并研究脂肪组织来源的外泌体(Ad-exosomes)对小鼠肌肉(C2C12 细胞)和肝细胞系(AML12 细胞)的影响。

方法和结果

本研究从正常饮食喂养的小鼠或高脂肪饮食(HFD)喂养的肥胖小鼠的脂肪组织中分离出外泌体,并证实其可被分化的 C2C12 和 AML12 细胞摄取。来自 HFD 喂养肥胖小鼠的 Ad-exosomes 可诱导 C2C12 和 AML12 细胞发生胰岛素抵抗、甘油三酯(TG)积累、内质网应激和炎症。有趣的是,本研究发现,与分化的 C2C12 细胞相比,来自 HFD 喂养肥胖小鼠的 Ad-exosomes 诱导的 TG 积累在 AML12 细胞中显著增加,而相同处理后细胞的葡萄糖摄取在 C2C12 细胞中减少,在 AML12 细胞中增加。此外,来自 HFD 喂养肥胖小鼠的 Ad-exosomes 不仅引起 TG 积累,还引起 AML12 细胞中的脂生成。

结论

结果表明,来自 HFD 喂养肥胖小鼠的 Ad-exosomes 可引起肌肉和肝脏的胰岛素抵抗,但它们在胰岛素抵抗发展过程中对代谢的影响在不同组织中有所不同。

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