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The present study evaluated the therapeutic effects of the newly identified bouchardatine (Bou) on obesity\u2010associated metabolic disorders and the molecular mechanisms of these effects.<\/jats:p><\/jats:sec><jats:sec><jats:title>Experimental approach<\/jats:title><jats:p>The molecular mode of action of Bou for its effects on lipid metabolism was first examined in 3T3\u2010L1 adipocytes and HepG2 cells. This was followed by an evaluation of its metabolic effects in mice fed a high\u2010fat diet for 16\u00a0weeks with Bou being administered in the last 5\u00a0weeks. Further mechanistic investigations were conducted in pertinent organs of the mice and relevant cell models.<\/jats:p><\/jats:sec><jats:sec><jats:title>Key results<\/jats:title><jats:p>In 3T3\u2010L1 adipocytes, Bou reduced lipid content and increased sirtuin 1 (SIRT1) activity to facilitate liver kinase B1 (LKB1) activation of AMPK. Chronic administration of Bou (50\u00a0mg\u2219kg<jats:sup>\u22121<\/jats:sup> every other day) in mice significantly attenuated high\u2010fat diet\u2010induced increases in body weight gain, dyslipidaemia and fatty liver without affecting food intake and no adverse effects were detected. These metabolic effects were associated with activation of the SIRT1\u2013LKB1\u2013AMPK signalling pathway in adipose tissue and liver. Of particular note, UCP1 expression and mitochondrial biogenesis were increased in both white and brown adipose tissues of Bou\u2010treated mice. Incubation with Bou induced similar changes in primary brown adipocytes isolated from mice<jats:bold>.<\/jats:bold><\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions and implications<\/jats:title><jats:p>Bou may have therapeutic potential for obesity\u2010related metabolic diseases by increasing the capacity of energy expenditure in adipose tissues and liver through a mechanism involving the SIRT1\u2013LKB1\u2013AMPK axis.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bph.13855","type":"journal-article","created":{"date-parts":[[2017,5,11]],"date-time":"2017-05-11T13:16:05Z","timestamp":1494508565000},"page":"2457-2470","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":49,"title":["Natural alkaloid bouchardatine ameliorates metabolic disorders in high\u2010fat diet\u2010fed mice by stimulating the sirtuin 1\/liver kinase B\u20101\/AMPK 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