lørdag den 25. august 2018

FAM13A, fatty acid oxidation and ME

Lipid metabolism is dysregulated in ME patients (1, 2, 3, 4).

Family with sequence similarity 13 number A (FAM13A) regulates fatty acid oxidation (FAO) (5).

The gene FAM13A is hypomethylated (TSS200 and TSS1500) in peripheral blood mononuclear cells (PBMC) from ME patients (table S4 in ref 6).

The gene FAM13A is hypermethylated (1stExon/5'UTR), CPT1A is hypermethylated (5'UTR) and CPT1B is hypermethylated (TSS200/5'UTR) in PBMC from ME patients. This DNA methylation pattern is related to quality of life in the ME patients (table S7 in ref 7).

In whole blood from adolescent CFS patients FAM13A gene expression is elevated (table S3 in ref 8).

Use the link to see the figure:
Figure. FAM13A regulates the CPT1A–FAO pathway in chronic obstructive pulmonary disease (COPD).  (Ref. 5)

FAM13A regulates the CPT1A–FAO pathway in chronic obstructive pulmonary disease (COPD). FAM13 locus has been shown to be associated with increased expression of FAM13A and higher risk for COPD. FAM13 in association with SIRT1 induces the expression of CPT1A, a key enzyme that regulates fatty acid oxidation (FAO) in the mitochondria. Up-regulation of CPT1A promotes FAO and high production of ROS, leading to lung epithelial cell death; this is an important pathogenic mechanism that might lead to COPD. CAT, carnitine translocase; CoA, coenzyme A; CPT1A, carnitine palmitoyltransferase 1; CPT2, carnitine palmitoyltransferase 2; FACS, fatty acyl-CoA synthase; FADH2, flavin adenin dinucleotide; FAM13A, family with sequence similarity 13 member A; NADH, nicotinamide adenine dinucleotide reduced; ROS, reactive oxygen species; SIRT1, sirtuin 1; TCA, tricarboxylic acid cycle.  (Ref. 5)

Is FAM13A and CPT1A/CPT1B involved in the ME/CFS pathomechanism?

  1. Naviaux et al: Metabolic features of CFS. www.pnas.org/cgi/doi/10.1073/pnas.1607571113
  2. Germain et al: Metabolic profiling of a ME/CFS discovery cohort reveals disturbances in fatty acid and lipid metabolism. Mol. BioSyst. 2017, 13, 371.
  3. Nagy-Szakal et al: Insights into ME/CFS phenotypes through comprehensive metabolomics. Nat Sci Rep 2018, 8.
  4. Reuter and Evans: Long-chain acylcarnitine deficiency in patients with CFS. Potential involvement of altered carnitine palmitoyltransferase-I-activity. J. Int. Med. 2011, 270.
  5. Hawkins et al. FAM13A, A Fatty Acid Oxidation Switch in Mitochondria. Friend or Foe in Chronic Obstructive Pulmonary Disease Pathogenesis?  Am J Respir Cell Mol Biol. 2017 Jun; 56(6): 689–691.doi: 10.1165/rcmb.2017-0080ED  https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5516298/
  6. Trivedi et al: Identification of ME/CFS - associated DNA methylation patterns. Plos One 2018, 13, 7.
  7. de Vega et al: Epigenetic modifications and glucocorticoid sensitivity in ME/CFS. BMC Medical Genomics, 2017, 10, 11.
  8. Nguyen et al: Whole blood gene expression in adolescent CFS: an exploratory crosssectional study suggesting altered B cell differentiation and survival. J Transl Med. 2017,15,102

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