Features of an altered AMPK metabolic pathway in Gilbert's Syndrome, and its role in metabolic health

Autoren:Mölzer, Christine; Wallner, Marlies; Kern, Carina; Tosevska, Anela; Schwarz, Ursula; Zadnikar, Rene (Medizinische Universität Wien); Doberer, Daniel (Medizinische Universität Wien); Marculescu, Rodrig; Wagner, Karl-Heinz
Abstrakt:

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.

Sprache:Englisch
Publikationsdatum:2016
Journaltitel:Scientific Reports
Volume:6
Seiten:30051
Peer reviewed:true
Links:http://phaidra.univie.ac.at/o:514796
Digital Object Identifier (DOI):http://dx.doi.org/10.1038/srep30051
Publikationstyp:Artikel
Portal:https://ucris.univie.ac.at/portal/en/publications/features-of-an-altered-ampk-metabolic-pathway-in-gilberts-syndrome-and-its-role-in-metabolic-health(bce25870-df0c-4b72-8026-6be4f409fedb).html