MOTS-c Peptide Levels Linked to Liver Fibrosis and Metabolic Health in MAFLD
Background
Metabolic Dysfunction-Associated Fatty Liver Disease (MAFLD) is a prevalent chronic liver condition characterized by excessive fat accumulation in the liver, often progressing to liver fibrosis, cirrhosis, and even hepatocellular carcinoma. It is strongly associated with metabolic risk factors like obesity, type 2 diabetes, and dyslipidemia. Despite its widespread impact, the precise role of novel metabolic regulators in MAFLD progression remains unclear, and effective non-invasive biomarkers for fibrosis severity are urgently needed. This study specifically aimed to investigate the relationship between circulating levels of the mitochondrial-derived peptide MOTS-c and the severity of liver fibrosis, as well as various metabolic components, in patients diagnosed with MAFLD.
Results
The study revealed significant inverse correlations between circulating MOTS-c levels and markers of liver fibrosis severity. Patients with advanced liver fibrosis (FIB-4 index > 3.25) exhibited significantly lower mean MOTS-c concentrations (2.8 ± 0.7 ng/mL) compared to those with mild fibrosis (4.5 ± 0.9 ng/mL, p<0.001). Furthermore, MOTS-c levels were inversely correlated with HOMA-IR (r = -0.48, p<0.001) and positively correlated with HDL-cholesterol (r = 0.35, p<0.005), indicating a link to improved insulin sensitivity and lipid profiles. A 1 ng/mL increase in circulating MOTS-c was independently associated with a 28% reduction in the odds of having significant liver fibrosis (p<0.001), after adjusting for age, BMI, and diabetes status. These findings suggest that higher MOTS-c levels are associated with better metabolic health and less severe liver damage in MAFLD patients, with a 2.1-fold difference in average MOTS-c levels between the lowest and highest fibrosis groups.
Why It Matters
This study provides compelling evidence that circulating MOTS-c levels are significantly associated with both metabolic health and the severity of liver fibrosis in patients with MAFLD. The consistent inverse relationship suggests that MOTS-c could serve as a novel and easily accessible biomarker for assessing MAFLD progression and identifying individuals at higher risk of advanced liver disease. Furthermore, these findings open avenues for exploring MOTS-c as a potential therapeutic target to mitigate metabolic dysfunction and halt or even reverse liver fibrosis in MAFLD patients. Future research should focus on interventional studies to determine if modulating MOTS-c levels can directly impact disease outcomes, potentially leading to new Phase II human trials.