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

Sci Rep. 2016 Jul 21:6:30051. doi: 10.1038/srep30051.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • AMP-Activated Protein Kinases / analysis*
  • AMP-Activated Protein Kinases / genetics
  • Adolescent
  • Adult
  • Case-Control Studies
  • Female
  • Gene Expression Profiling
  • Gilbert Disease / pathology*
  • Humans
  • Leukocytes, Mononuclear / enzymology*
  • Male
  • Metabolic Networks and Pathways*
  • Middle Aged
  • Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha / analysis*
  • Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha / genetics
  • Peroxisome Proliferator-Activated Receptors / analysis*
  • Peroxisome Proliferator-Activated Receptors / genetics
  • Young Adult


  • Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
  • Peroxisome Proliferator-Activated Receptors
  • AMP-Activated Protein Kinases