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 AMPK?1 gene expression), levels of functioning proteins (phospho-AMPK ?1/?2, PgC 1 ?, Ppar ? and ?) were measured in PBMCs (peripheral blood mononucleated cells). In GS individuals, rates of phospho-AMPK ?1/?2, -Ppar ?/? and of PgC 1? were significantly higher, attesting to a boosted fasting response in this condition. In line with this finding, AMPK?1 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.

SUBMITTER: Molzer C 

PROVIDER: S-EPMC4956769 | biostudies-literature | 2016 Jul

REPOSITORIES: biostudies-literature