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Author Spotlight: Establishing MASLD Cell Models for Investigating Disease Mechanisms and the Lipid-Lowering Effects of Koumiss
Published on: July 19, 2024
Updated mechanisms of MASLD pathogenesis
Yuxuan Li1,2, Peipei Yang2, Jialu Ye2
1Department of Cardiology, State Key Laboratory of Transvascular Implantation Devices, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
Abstract:
Metabolic dysfunction-associated steatotic liver disease (MASLD) has garnered considerable attention globally. Changing lifestyles, over-nutrition, and physical inactivity have promoted its development. MASLD is typically accompanied by obesity and is strongly linked to metabolic syndromes. Given that MASLD prevalence is on the rise, there is an urgent need to elucidate its pathogenesis. Hepatic lipid accumulation generally triggers lipotoxicity and induces MASLD or progress to metabolic dysfunction-associated steatohepatitis (MASH) by mediating endoplasmic reticulum stress, oxidative stress, organelle dysfunction, and ferroptosis. Recently, significant attention has been directed towards exploring the role of gut microbial dysbiosis in the development of MASLD, offering a novel therapeutic target for MASLD. Considering that there are no recognized pharmacological therapies due to the diversity of mechanisms involved in MASLD and the difficulty associated with undertaking clinical trials, potential targets in MASLD remain elusive. Thus, this article aimed to summarize and evaluate the prominent roles of lipotoxicity, ferroptosis, and gut microbes in the development of MASLD and the mechanisms underlying their effects. Furthermore, existing advances and challenges in the treatment of MASLD were outlined.
Insights
Metabolic dysfunction-associated steatotic liver disease (MASLD) is rising due to lifestyle changes. This review explores lipotoxicity, ferroptosis, and gut microbes in MASLD development and treatment challenges.
Area of Science:
- Hepatology
- Metabolic Diseases
- Microbiome Research
Background:
- Metabolic dysfunction-associated steatotic liver disease (MASLD) prevalence is increasing globally, linked to lifestyle factors like over-nutrition and inactivity.
- MASLD is associated with obesity and metabolic syndromes, necessitating a deeper understanding of its pathogenesis.
- Hepatic lipid accumulation can lead to lipotoxicity, endoplasmic reticulum stress, oxidative stress, organelle dysfunction, and ferroptosis, driving MASLD and its progression to MASH.
Purpose of the Study:
- To summarize and evaluate the roles of lipotoxicity, ferroptosis, and gut microbes in MASLD pathogenesis.
- To elucidate the underlying mechanisms of these factors in MASLD development.
- To outline current advances and challenges in MASLD treatment.
Main Methods:
- Literature review and synthesis of existing research on MASLD.
- Evaluation of the mechanisms linking lipotoxicity, ferroptosis, and gut dysbiosis to liver disease.
- Analysis of current therapeutic strategies and their limitations.
Main Results:
- Hepatic lipotoxicity, ferroptosis, and gut microbial dysbiosis are key contributors to MASLD development.
- These factors mediate cellular stress and organelle dysfunction, promoting liver steatosis and inflammation.
- The complex interplay of these elements presents significant challenges for developing effective pharmacological therapies.
Conclusions:
- Targeting lipotoxicity, ferroptosis, and gut microbiota represents a promising avenue for MASLD intervention.
- Further research is needed to overcome the challenges in clinical trials and identify effective treatments.
- Understanding these pathogenic mechanisms is crucial for developing novel therapeutic strategies for MASLD.
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