The relationship of circulating MOTS-c level with liver fibrosis and metabolic components in patients with metabolic dysfunction-associated fatty liver disease.

OBJECTIVE: Mitochondrial open reading frame of the 12s ribosomal RNA type-c (MOTS-c) is a novel identified mitochondrial signal transmission peptide that plays an important role in glucose, amino acid and lipid metabolism. In this study, we aimed to investigate the relationship of circulating MOTS-c level with noninvasive scores of fibrosis and the components of metabolic syndrome (MetS) in patients with metabolic dysfunction-associated fatty liver disease (MAFLD). PATIENTS AND METHODS: This was a single-center cross-sectional study, and the participants were divided into two groups based on their liver ultrasound results: the fatty liver group and the healthy control group. The MOTS-c level was measured by the ELISA method. Non-alcoholic fatty liver disease fibrosis score (NFS) and fibrosis 4 (FIB-4) were used to determine the level of liver fibrosis. Statistical analyses were performed using Statistical Package for Social Science 15.0 package program. RESULTS: One hundred fifty patients (male, n=57) with MAFLD [median age 41.0 (14) years] and 84 healthy controls (male, n=34) [median age 36.0 (22) years] were included in this study. Patients with MAFLD had significantly lower MOTS-c levels than the healthy controls (p=0.009). The MOTS-c level was significantly lower in subjects with MetS (n=48) compared to those without MetS (n=186) (p=0.01). In the total population (n=234), MOTS-c levels negatively correlated with the presence of MAFLD, NFS, FIB-4, and components of MetS. CONCLUSIONS: Individuals diagnosed with MetS and MAFLD tend to have lower levels of MOTS-c. Additionally, these lower levels are inversely correlated with both the components of MetS and noninvasive fibrosis scores. MAFLD negatively correlated to the MetS components and noninvasive scores of fibrosis.

Microvesicular steatosis: a missed item in the management of nonalcoholic fatty liver disease?

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is among the most common causes of chronic liver disease and cirrhosis. In NAFLD, histological course of steatosis is usually macrovesicular (MacroS), but it may be accompanied by varying degrees of microvesicular steatosis (MicroS). Thus, in this study, we aimed to evaluate the prevalence and significance of MicroS in subjects with NAFLD. METHODS: A retrospective analysis of clinical and laboratory data of patients with histologically proven NAFLD was performed. The liver biopsy specimens which stained with hematoxylin eosin, reticulin, and Masson's Trichrome stains were evaluated by single expert liver pathologist. Scoring and semiquantitative assessment of steatosis and NAFLD severity was done according to Kleiner scale known as NAFLD activity score (NAS). Grading for steatosis, steatosis type, zonal distribution of steatosis and other histological findings were also determined. RESULTS: The prevalence of MicroS among the study population (n= 191) was 30.4%. There was no difference regarding the demographic and biochemical parameters between patients with or without MicroS. On the other hand, the prevalence of ballooning injury and megamitochondria were higher in patients with MicroS (p= 0.019 and p= 0.036, respectively). There was a significant association of MicroS with ballooning injury (OR 2.65, 95% CI= 1.26-5.55 ; p= 0.005) and the presence of megamitochondria (OR 3.72, 95% CI= 1.00-13.72 ; p= 0.037). CONCLUSION: MicroS is common in patients with NAFLD and is associated with early histological findings in this clinically relevant condition. Further longitudinal studies are needed to characterize the role of MicroS in the natural history of NAFLD.

Species-specific double-strand break repair and genome evolution in plants.

Even closely related eukaryotic species may differ drastically in genome size. While insertion of retroelements represents a major source of genome enlargement, the mechanism mediating species- specific deletions is fairly obscure. We analyzed the formation of deletions during double-strand break (DSB) repair in Arabidopsis thaliana and tobacco, two dicotyledonous plant species differing >20-fold in genome size. DSBs were induced by the rare cutting restriction endonuclease I-SCE:I and deletions were identified by loss of function of a negative selectable marker gene containing an I-SCE:I site. Whereas the partial use of micro-homologies in junction formation was similar in both species, in tobacco 40% of the deletions were accompanied by insertions. No insertions could be detected in Arabidopsis , where larger deletions were more frequent, indicating a putative inverse correlation between genome size and the average length of deletions. Such a correlation has been postulated before by a theoretical study on the evolution of related insect genomes and our study now identifies a possible molecular cause for the phenomenon, indicating that species-specific differences in DSB repair might indeed influence genome evolution.