News > Metabomeeting 2015


Metabomeeting 2015


Organized by the Metabolic Profiling Forum (MPF) and SELECTBIO

When: 7-9 December 2015


Where: Robinson College, Cambridge, UK


Attendees from OWL: Dr. Rebeca Mayo


Poster title: (#159) Mechanisms leading to nonalcoholic steatohepatitis: subtyping for the development of effective treatments




Nonalcoholic steatohepatitis (NASH) is a histological definition that groups together defects in diverse biochemical processes causing hepatic fat accumulation, inflammation, necrosis and fibrosis. The identification of the types of mechanisms leading to NASH and the discovery of noninvasive biomarkers of NASH’ subtypes are central for the development of effective treatments.
Hepatic biosynthesis of S-adenosylmethionine (SAMe), or MAT reaction was selected as starting point. Hepatic MAT deletion (Mat1a KO) in mice leads to the spontaneous development of NASH. NASH patients often show reduced expression of MAT1A.
Ablation of Mat1a in mice led to a substantial reduction in hepatic methylthioadenosine and PUFA-PC, whereas methionine, PUFA-PE and methylneogenic substrates were more abundant. SAMe depletion impairs liver’s capacity to adapt TG synthesis to its rate of export via VLDL, accumulating TG, DG and FA. This is explained by the exhaustion of mitochondrial FA oxidation and increased FA uptake.
Finally, it was identified a serum metabolomic profile that could differentiate between Mat1a and WT mice (M-type fingerprint). To translate the findings to humans, an unsupervised cluster analysis using serum of patients with biopsy-proven NASH (n=134) was carried out. Patients were classified into two clusters, showing 63 patients (47%) the M-type NASH serum metabolic profile.

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