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

Autor(en)

Christine Mölzer, Marlies Wallner, Carina Kern, Anela Tosevska, Ursula Schwarz, Rene Zadnikar, Daniel Doberer, Rodrig Marculescu, Karl-Heinz Wagner

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.

Organisation(en)

Department für Ernährungswissenschaften

Externe Organisation(en)

Fachhochschule Joanneum, Medizinische Universität Wien

Journal

Scientific Reports

Band

6

Seiten

1-15

Anzahl der Seiten

15

ISSN

2045-2322

DOI

https://doi.org/10.1038/srep30051

Publikationsdatum

07-2016

Peer-reviewed

Ja

ÖFOS 2012

303009 Ernährungswissenschaften

Schlagwörter

Sustainable Development Goals

SDG 3 – Gesundheit und Wohlergehen

Link zum Portal

https://ucrisportal.univie.ac.at/de/publications/bce25870-df0c-4b72-8026-6be4f409fedb