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Based on observations that individuals with Gilbert\u2019s syndrome (GS; <jats:italic>UGT1A1<\/jats:italic><jats:sup>*<\/jats:sup>28 promoter mutation) are generally lighter, leaner and healthier than controls, specific inter-group differences in the AMPK pathway regulation were explored. Therefore, a case-control study involving 120 fasted, healthy, age- and gender matched subjects with\/without GS, was conducted. By utilising intra-cellular flow cytometry (next to assessing <jats:italic>AMPK\u03b11<\/jats:italic> gene expression), levels of functioning proteins (phospho-AMPK \u03b11\/\u03b12, PgC 1 \u03b1, Ppar \u03b1 and \u03b3) were measured in PBMCs (peripheral blood mononucleated cells). In GS individuals, rates of phospho-AMPK \u03b11\/\u03b12, -Ppar \u03b1\/\u03b3 and of PgC 1\u03b1 were significantly higher, attesting to a boosted fasting response in this condition. In line with this finding, <jats:italic>AMPK\u03b11<\/jats:italic> gene expression was equal between the groups, possibly stressing the post-translational importance of boosted fasting effects in GS. In reflection of an apparently improved health status, GS individuals had significantly lower BMI, glucose, insulin, C-peptide and triglyceride levels. Herewith, we propose a new theory to explain why individuals having GS are leaner and healthier, and are therefore less likely to contract metabolic diseases or die prematurely thereof.<\/jats:p>","DOI":"10.1038\/srep30051","type":"journal-article","created":{"date-parts":[[2016,7,22]],"date-time":"2016-07-22T05:32:20Z","timestamp":1469165540000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":45,"title":["Features of an altered AMPK metabolic pathway in Gilbert\u2019s Syndrome, and its role in metabolic health"],"prefix":"10.1038","volume":"6","author":[{"given":"Christine","family":"M\u00f6lzer","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marlies","family":"Wallner","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carina","family":"Kern","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anela","family":"Tosevska","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ursula","family":"Schwarz","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rene","family":"Zadnikar","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniel","family":"Doberer","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rodrig","family":"Marculescu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Karl-Heinz","family":"Wagner","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2016,7,21]]},"reference":[{"key":"BFsrep30051_CR1","doi-asserted-by":"publisher","first-page":"98","DOI":"10.1097\/MOL.0b013e328328d0a4","volume":"20","author":"C Cant\u00f3","year":"2009","unstructured":"Cant\u00f3, C. & Auwerx, J. 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