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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

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

Mölzer Christine C Wallner Marlies M Kern Carina C Tosevska Anela A Schwarz Ursula U Zadnikar Rene R Doberer Daniel D Marculescu Rodrig R Wagner Karl-Heinz KH

Scientific reports 20160721

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 sub ...[more]

PMID: 27444220

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Project description:BACKGROUND:The molecular basis of compensatory growth in monogastric animals has not yet been fully explored. Herewith, in this study we aim to determine changes in the pig skeletal muscle transcriptome profile during compensatory growth following a feed restriction period. A RNA-Seq experiment was performed with a total of 24 females belonging to a Duroc commercial line. Half of the animals received either a restricted (RE) or ad libitum (AL) diet during the first fattening period (60-125 d of age). After that, all gilts were fed ad libitum for a further ~30 d until the age of ~155 d, when animals were slaughtered and samples of gluteus medius muscle were harvested to perform RNA-Seq analyses and intramuscular fat content determination. RESULTS:During the period following food restriction, RE animals re-fed ad libitum displayed compensatory growth, showed better feed conversion rate and tended to deposit more subcutaneous fat than AL fed animals. Animals were slaughtered in the phase of accelerated growth, when RE animals had not completely compensated the performance of AL group, showing lower live and carcass weights. At intramuscular level, RE gilts showed a higher content of polyunsaturated fatty acids during the compensatory growth phase. The comparison of RE and AL expression profiles allowed the identification of 86 (?log2Fold-Change??>?1, padj?<?0.05) differentially expressed (DE) genes. A functional categorization of these DE genes identified AMPK Signaling as the most significantly enriched canonical pathway. This kinase plays a key role in the maintenance of energy homeostasis as well as in the activation of autophagy. Among the DE genes identified as components of AMPK Signaling pathway, five out of six genes were downregulated in RE pigs. CONCLUSIONS:Animals re-fed after a restriction period exhibited a less oxidative metabolic profile and catabolic processes in muscle than animals fed ad libitum. The downregulation of autophagy observed in the skeletal muscle of pigs undergoing compensatory growth may constitute a mechanism to increase muscle mass thus ensuring an accelerated growth rate. These results reveal that the downregulation of AMPK Signaling plays an important role in compensatory growth in pigs.

Dataset Information

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

Publications

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

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