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<p>Adipose tissue dysfunction drives hepatic lipid overload in metabolic dysfunction-associated steatotic liver disease (MASLD), yet the involvement of adipose tissue-derived small extracellular vesicles (sEVs) remains unclear. Herein, we showed that transplanting adipose tissue from high‑fat diet (HFD)-fed male mice exacerbated insulin resistance and hepatic steatosis in lean recipients. Adipose‑specific Sirt3 overexpression (<i>Sirt3</i><sup><i>AKI</i></sup>) alleviated insulin resistance and liver steatosis in HFD-fed male mice, whereas adipose‑specific Sirt3 knockdown aggravated these phenotypes. Moreover, adipose sEV miRNAs regulated hepatic lipid metabolism in <i>Sirt3</i><sup><i>AKI</i></sup> male mice. MicroRNA sequencing identified miR-30a-3p was increased in the circulating sEVs from HFD-fed male mice, while decreased in sEVs from <i>Sirt3</i>OE adipocytes and <i>Sirt3</i><sup><i>AKI</i></sup> male mice. Mechanistically, miR‑30a‑3p promoted hepatic steatosis by targeting <i>Becn1</i>; this process was suppressed when Sirt3 downregulated miR‑30a‑3p transcription via deacetylation of H3K56. These findings highlight the critical role of adipose sEV microRNAs in driving hepatocyte lipotoxicity, and suggest miR-30a-3p inhibition as a promising MASLD therapy.</p>

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Adipocyte small extracellular vesicle-derived microRNA-30a-3p exacerbates hepatic steatosis in high fat diet-fed male mice

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年4月11日

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  • Tian Zhang,
  • Longkun Hu,
  • Diao Chen,
  • Yongxin Chen,
  • Fei Zhou,
  • Ruohan Lou,
  • Yuxia Zhou,
  • Yuanyuan Wang,
  • Mingjun Shi,
  • Ke-Gang Linghu,
  • Ligen Lin,
  • Bing Guo

摘要

Adipose tissue dysfunction drives hepatic lipid overload in metabolic dysfunction-associated steatotic liver disease (MASLD), yet the involvement of adipose tissue-derived small extracellular vesicles (sEVs) remains unclear. Herein, we showed that transplanting adipose tissue from high‑fat diet (HFD)-fed male mice exacerbated insulin resistance and hepatic steatosis in lean recipients. Adipose‑specific Sirt3 overexpression (Sirt3AKI) alleviated insulin resistance and liver steatosis in HFD-fed male mice, whereas adipose‑specific Sirt3 knockdown aggravated these phenotypes. Moreover, adipose sEV miRNAs regulated hepatic lipid metabolism in Sirt3AKI male mice. MicroRNA sequencing identified miR-30a-3p was increased in the circulating sEVs from HFD-fed male mice, while decreased in sEVs from Sirt3OE adipocytes and Sirt3AKI male mice. Mechanistically, miR‑30a‑3p promoted hepatic steatosis by targeting Becn1; this process was suppressed when Sirt3 downregulated miR‑30a‑3p transcription via deacetylation of H3K56. These findings highlight the critical role of adipose sEV microRNAs in driving hepatocyte lipotoxicity, and suggest miR-30a-3p inhibition as a promising MASLD therapy.