Mitochondrial Quality Control: Its Role in Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD).
Soyeon ShinJaeyoung KimJu Yeon LeeJun KimChang-Myung OhPublished in: Journal of obesity & metabolic syndrome (2023)
Metabolic dysfunction-associated steatotic liver disease (MASLD), formerly known as non-alcoholic fatty liver disease, is characterized by hepatic steatosis and metabolic dysfunction and is often associated with obesity and insulin resistance. Recent research indicates a rapid escalation in MASLD cases, with projections suggesting a doubling in the United States by 2030. This review focuses on the central role of mitochondria in the pathogenesis of MASLD and explores potential therapeutic interventions. Mitochondria are dynamic organelles that orchestrate hepatic energy production and metabolism and are critically involved in MASLD. Dysfunctional mitochondria contribute to lipid accumulation, inflammation, and liver fibrosis. Genetic associations further underscore the relationship between mitochondrial dynamics and MASLD susceptibility. Although U.S. Food and Drug Administration-approved treatments for MASLD remain elusive, ongoing clinical trials have highlighted promising strategies that target mitochondrial dysfunction, including vitamin E, metformin, and glucagon-like peptide-1 receptor agonists. In preclinical studies, novel therapeutics, including nicotinamide adenine dinucleotide + precursors, urolithin A, spermidine, and mitoquinone, have shown beneficial effects, such as improving mitochondrial quality control, reducing oxidative stress, and ameliorating hepatic steatosis and inflammation. In conclusion, mitochondrial dysfunction is central to MASLD pathogenesis. The innovative mitochondria-targeted approaches discussed in this review offer a promising avenue for reducing the burden of MASLD and improving global quality of life.
Keyphrases
- oxidative stress
- quality control
- liver fibrosis
- insulin resistance
- drug administration
- cell death
- endoplasmic reticulum
- reactive oxygen species
- diabetic rats
- clinical trial
- dna damage
- induced apoptosis
- ischemia reperfusion injury
- metabolic syndrome
- type diabetes
- adipose tissue
- skeletal muscle
- high fat diet induced
- weight loss
- genome wide
- high fat diet
- risk factors
- randomized controlled trial
- mesenchymal stem cells
- risk assessment
- polycystic ovary syndrome
- cell therapy
- drug delivery
- weight gain
- bone marrow
- signaling pathway
- cancer therapy
- dna methylation
- case control
- human health