Metabolomic tissue signature in human non-alcoholic fatty liver disease identifies protective candidate metabolites.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disorder in industrialized countries, yet its pathophysiology is incompletely understood. Small-molecule metabolite screens may offer new insights into disease mechanisms and reveal new treatment targets. METHODS: Discovery (N = 33) and replication (N = 66) of liver biopsies spanning the range from normal liver histology to non-alcoholic steatohepatitis (NASH) were ascertained ensuring rapid freezing under 30 s in patients. 252 metabolites were assessed using GC/MS. Replicated metabolites were evaluated in a murine high-fat diet model of NAFLD. RESULTS: In a two-stage metabolic screening, hydroquinone (HQ, p(combined) = 3.0 × 10(-4)) and nicotinic acid (NA, p(combined) = 3.9 × 10(-9)) were inversely correlated with histological NAFLD severity. A murine high-fat diet model of NAFLD demonstrated a protective effect of these two substances against NAFLD: Supplementation with 1% HQ reduced only liver steatosis, whereas 0.6% NA reduced both liver fat content and serum transaminase levels and induced a complex regulatory network of genes linked to NALFD pathogenesis in a global expression pathway analysis. Human nutritional intake of NA equivalent was also consistent with a protective effect of NA against NASH progression. CONCLUSION: This first small-molecular screen of human liver tissue identified two replicated protective metabolites. Either the use of NA or targeting its regulatory pathways might be explored to treat or prevent human NAFLD.

Analysis of gene expression in amyloplasts of potato tubers.

Gene expression in amyloplasts derived from potato tubers was analyzed at the levels of transcription, mRNA accumulation and formation of polysomes. Compared with chloroplasts, overall transcriptional activity is considerably reduced in amyloplasts. Nevertheless, several transcripts are synthesized in amyloplasts during growth of tubers. Among the transcribed amyloplast genes are the ribosomal operon and the psbA gene. Primer extension analysis provided evidence that in amyloplasts the plastid encoded RNA polymerase (PEP) is the principal RNA polymerase involved in the transcription of the rrn operon. Analysis of plastid steady state transcripts showed that there are only small differences in the levels of specific transcripts between amyloplasts and chloroplasts. With respect to the low transcription rate of the accumulating RNA-species in amyloplasts, a high stability of these transcripts is obvious. Though amyloplasts possess polysomes, specific mRNAs associated with such polysomes could not be detected. This suggests that translation could be impaired in amyloplasts, which, in turn, implies that these organelles are not suitable targets for the expression of transgenes introduced into the plastid genome by plastid transformation.