{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T16:23:13Z","timestamp":1783527793049,"version":"3.55.0"},"reference-count":28,"publisher":"Bioscientifica","issue":"4","content-domain":{"domain":["journals.bioscientifica.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2025,11,1]]},"abstract":"<jats:p>Insulin resistance is often characterized as the factor that contributes to the emergence of metabolic diseases. Hepatic microRNAs (miRNAs) played critical roles in the development of metabolic-associated steatotic liver disease (MASLD) and insulin resistance. To investigate the effects of hepatic miR-411-5p in regulating insulin resistance, the present study utilized primary mouse hepatocytes and mice with MASLD. Suppression of miR-411-5p decreased hepatocyte glycogen production and phosphorylation of AKT, but miR-411-5p mimic improved insulin sensitivity. Mechanistically, 3\u2032-UTR of transcription factor Sp2 was one of the binding sites of miR-411-5p. Treatment of miR-411-5p mimic suppressed the Sp2 mRNA and protein levels, enhancing the insulin signaling activity in the primary mouse hepatocytes. Hepatocyte-specific overexpression of Sp2 induced hepatic lipid accumulation and activation of related metabolic pathways. In contrast, inhibition of miR-411-5p reversely upregulated the expression of Sp2 and exaggerated insulin resistance in primary hepatocytes and the mouse model. Similarly, miR-411-5p mimic decreased obesity-induced hyperinsulinemia, glucose intolerance, insulin intolerance, and pyruvate intolerance. Furthermore, the parameters of MASLD, including lipid deposits, inflammation, and fibrosis, were improved after miR-411-5p replenishment, but co-administration with adeno-associated virus (AAV)-Sp2 abolished these benefits in the obese mouse model. Taken together, these findings demonstrated that Sp2-dependent miR-411-5p action regulates insulin resistance and MASLD, which provides a therapeutic approach toward resolving insulin resistance.<\/jats:p>","DOI":"10.1530\/jme-24-0156","type":"journal-article","created":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T17:44:27Z","timestamp":1760031867000},"update-policy":"https:\/\/doi.org\/10.1530\/crossmarkpolicy-6","source":"Crossref","is-referenced-by-count":1,"title":["MicroRNA-411-5p alleviates hepatic insulin resistance via suppressing transcription factor Sp2 in MASLD 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