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Despite the promising outlook for hyperlipidaemia treatment, the need persists for the development of lipid\u2010lowering agents with heightened efficiency and minimal toxicity. This investigation aims to elucidate the lipid\u2010lowering effects and potential pharmacodynamic mechanisms of Anti\u2010b, a novel low MW compound.<\/jats:p><\/jats:sec><jats:sec><jats:title>Experimental Approach<\/jats:title><jats:p>We employed high\u2010fat diet (HFD) in hamsters and mice or oleic acid (OA) in cultures of HepG2 cells and LO2 cells to induce hyperlipidaemia models. We administered Anti\u2010b to assess its therapeutic effects on dyslipidaemia and hepatic steatosis. We used western blotting, RNA sequencing, GO and KEGG analysis, oil red O staining, along with molecular docking and molecular dynamics simulation to elucidate the mechanisms underlying the effects of Anti\u2010b.<\/jats:p><\/jats:sec><jats:sec><jats:title>Key Results<\/jats:title><jats:p>Anti\u2010b exhibited a substantial reduction in HFD\u2010induced elevation of blood lipids, liver weight to body weight ratio, liver diameter and hepatic fat accumulation. Moreover, Anti\u2010b demonstrated therapeutic effects in alleviating total cholesterol (TC), TG levels, and lipid accumulation derived from OA in HepG2 cells and LO2 cells. Mechanistically, Anti\u2010b selectively bound to the mTOR kinase protein and increased mTOR thermal stability, resulting in downregulation of phosphorylation level. Notably, Anti\u2010b exerted anti\u2010hyperlipidaemia effects by modulating PPAR\u03b3 and SREBP1 signalling pathways and reducing the expression level of mSREBP1 and PPAR\u03b3 proteins.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion and Implications<\/jats:title><jats:p>In conclusion, our study has provided initial data of a novel low MW compound, Anti\u2010b, designed and synthesised to target mTOR protein directly. Our results indicate that Anti\u2010b may represent a novel class of drugs for the treatment of hyperlipidemia and hepatic steatosis.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bph.17397","type":"journal-article","created":{"date-parts":[[2024,11,30]],"date-time":"2024-11-30T04:49:38Z","timestamp":1732942178000},"page":"1254-1272","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Anti\u2010b diminishes hyperlipidaemia and hepatic steatosis in hamsters and mice by suppressing the mTOR\/PPAR\u03b3 and mTOR\/SREBP1 signalling pathways"],"prefix":"10.1111","volume":"182","author":[{"given":"Yu","family":"Bian","sequence":"first","affiliation":[{"name":"Department of Pharmacology (National Key Laboratory of Frigid Zone Cardiovascular Diseases, the State\u2010Province Key Laboratories of Biomedicine\u2010Pharmaceutics of China, Key Laboratory of Cardiovascular Research, Ministry of Education), College of Pharmacy Harbin 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