title: Features of an altered AMPK metabolic pathway in Gilbert's Syndrome, and its role in metabolic health.
abstract: Energy metabolism, involving the ATP-dependent AMPK-PgC-Ppar pathway impacts metabolic health immensely, in that its impairment can lead to obesity, giving rise to disease. Based on observations that individuals with Gilbert's syndrome (GS; UGT1A1(*)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 AMPKα1 gene expression), levels of functioning proteins (phospho-AMPK α1/α2, PgC 1 α, Ppar α and γ) were measured in PBMCs (peripheral blood mononucleated cells). In GS individuals, rates of phospho-AMPK α1/α2, -Ppar α/γ and of PgC 1α were significantly higher, attesting to a boosted fasting response in this condition. In line with this finding, AMPKα1 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.
authors.affiliation: University of Vienna, Faculty of Life Sciences, Department of Nutritional Sciences, Althanstraβe 14 (UZA2), 1090 Vienna, Austria.
authors.forename: Christine
authors.initials: C
authors.lastname: Mölzer
authors.affiliation: University of Applied Sciences, FH JOANNEUM, Institute of Dietetics and Nutrition, Alte Poststraβe 149, 8020 Graz, Austria.
authors.forename: Marlies
authors.initials: M
authors.lastname: Wallner
authors.affiliation: Medical University of Vienna, Center for Physiology and Pharmacology, Institute of Pharmacology, Währinger Straβe 13A, 1090 Vienna, Austria.
authors.forename: Carina
authors.initials: C
authors.lastname: Kern
authors.affiliation: University of Vienna, Faculty of Life Sciences, Department of Nutritional Sciences, Althanstraβe 14 (UZA2), 1090 Vienna, Austria.
authors.forename: Anela
authors.initials: A
authors.lastname: Tosevska
authors.affiliation: University of Vienna, Faculty of Life Sciences, Department of Nutritional Sciences, Althanstraβe 14 (UZA2), 1090 Vienna, Austria.
authors.forename: Ursula
authors.initials: U
authors.lastname: Schwarz
authors.affiliation: Medical University of Vienna, Clinical Institute of Laboratory Medicine, Vienna General Hospital, Währinger Gürtel 18-20, 1090 Vienna, Austria.
authors.forename: Rene
authors.initials: R
authors.lastname: Zadnikar
authors.affiliation: Medical University of Vienna, Department of Clinical Pharmacology, Vienna General Hospital, Währinger Gürtel 18-20, 1090 Vienna, Austria.
authors.forename: Daniel
authors.initials: D
authors.lastname: Doberer
authors.affiliation: Medical University of Vienna, Clinical Institute of Laboratory Medicine, Vienna General Hospital, Währinger Gürtel 18-20, 1090 Vienna, Austria.
authors.forename: Rodrig
authors.initials: R
authors.lastname: Marculescu
authors.affiliation: University of Vienna, Faculty of Life Sciences, Department of Nutritional Sciences, Althanstraβe 14 (UZA2), 1090 Vienna, Austria.
authors.forename: Karl-Heinz
authors.initials: KH
authors.lastname: Wagner
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000032:analysis* / Q000235:genetics; D000293:Adolescent; D000328:Adult; D016022:Case-Control Studies; D005260:Female; D020869:Gene Expression Profiling; D005878:Gilbert Disease / Q000473:pathology*; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000201:enzymology*; D008297:Male; D053858:Metabolic Networks and Pathways; D008875:Middle Aged; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha / Q000032:analysis* / Q000235:genetics; D047492:Peroxisome Proliferator-Activated Receptors / Q000032:analysis* / Q000235:genetics; D055815:Young Adult
chemical_list: D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D047492:Peroxisome Proliferator-Activated Receptors; D055372:AMP-Activated Protein Kinases