|Image 1: This is you... well, not exactly. It's rather an animal model of human carnitine metabolis ;-)|
A soon to be published paper by Janin Keller and other researchers from the Institute of Animal Nutrition and Nutrition Psychology at the Justus-Liebig-University, in Gießen, the Institute of Agricultural and Nutritional Sciences at the Martin-Luther-University, in Halle-Wittenberg, and the Hans-Knöll-Institute, Research Group Systems Biology/Bioinformatic, in Jena (all in Germany, btw.), does now shed some light onto the more subtle, epigenetic effects of l-carnitine supplementation (Keller. 2011).
|Image 2: The calculation of human equivalent doses is a constant (unreliable) pain in my ass - either you don't have the adequate conversion ratio or you do not know how much an animal eats. weighs etc...|
|Figure 1: Liver free and total l-carnitine levels (in nmol/g) in growing piglets after 21-days of normal or carnitine supplemented feed (data adapted from Keller. 2011)|
we observed that 563 genes were differentially expressed by L-carnitine. This shows that supplemental L-carnitine influences gene expression in the liver of piglets and indicates that at least some of the biological effects of L-carnitine are mediated by altering gene transcription. [...] Gene term enrichment analysis revealed that the most frequent biological processes associated with L- carnitine supplementation were dealing with metabolic processes. This was not surprising considering that the main function of L-carnitine is to stimulate energy metabolism by acting as shuttling molecule for long-chain fatty acids which also enhances the metabolic flux of glucose through the glycolytic chain. This was also confirmed by clustering analysis showing that 6 out of the 10 top-ranked clusters were dealing with metabolic processes. Representative genes from one of these clusters dealing with metabolic processes (carboxylic acid metabolic process, oxoacid metabolic process, organic acid metabolic process) encoded proteins or enzymes involved in cellular fatty acid uptake (SLC27A6, solute carrier family 27/fatty acid transporter, member 6), fatty acid activation (ACSL3, Long-chain-fatty-acid-CoA ligase 3) and fatty acid β-oxidation (ACADSB, Acyl-CoA dehydrogenase, short/branched chain specific), and most of these genes including SLC27A6, ACSL3 and ACADSB were found to be significantly up-regulated by L-carnitine supplementation.Moreover, the researchers found that a whole host of genes (e.g. GLUT8, GCK and GPD1 more than 4x elevated) related to glucose metabolism (glucose transport, conversion of glucose into glucose 6-phosphate, and glycolysis, and hexose biosynthetic processes, like gluconeogenesis) and triglyceride metabolic and triglyceride biosynthetic processes were elevated, as well. Taken together this lead the scientists to conclude that the epigenetic changes that were induced by 21 days of (relatively) high-dose dietary l-carnitine supplementation suggest that the "conditionally essential" amino acid l-carnitine
- ... exerts its "well-known stimulatory effect [...] on fatty acid β-oxidation" at least partly by stimulating the transcription of genes involved in "cellular fatty acid uptake, fatty acid activation and β-oxidation"
- ... has profound beneficial effects on glucose metabolism and utilization, which are mediated "not only by [a genetically triggered] stimulation of glycolysis but also suppression of gluconeogenesis in the liver", and
- ... triggers genetic modifications which lead to an "inhibition of glycerolipid biosynthesis and stimulation of lipoprotein secretion and fatty acid catabolism", which contribute to its overall beneficial effects on lipid metabolism.