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Article

Macronutrient Modulation in Metabolic Dysfunction-Associated Steatotic Liver Disease—the Molecular Role of Fatty Acids compared with Sugars in Human Metabolism and Disease Progression

Sinéad M. Mullin, Aidan J. Kelly, Méabh B. Ní Chathail, Suzanne Norris, Christopher E. Shannon, Helen M. Roche 2025 International Journal of Multidisciplinary Studies and Innovative Researchs

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Abstract

Metabolic dysfunction-associated steatotic liver disease (MASLD) is a significant public health concern, with its progression to metabolic dysfunction-associated steatohepatitis (MASH) and fibrosis leading to severe outcomes including cirrhosis, hepatocellular carcinoma, and liver failure. Whereas obesity and excess energy intake are well-established contributors to the development and progression of MASLD, the distinct role of specific macronutrients is less clear. This review examines the mechanistic pathways through which dietary fatty acids and sugars contribute to the development of hepatic inflammation and fibrosis, offering a nuanced understanding of their respective roles in MASLD progression. In terms of addressing potential therapeutic options, human intervention studies that investigate whether modifying the intake of dietary fats and carbohydrates affects MASLD progression are reviewed. By integrating this evidence, this review seeks to bridge the gap in the understanding between the mechanisms of macronutrient-driven MASLD progression and the effect of altering the intake of these nutrients in the clinical setting and presents a foundation for future research into targeted dietary strategies for the treatment of the disease.

Identifier Metadata

Identifier	110.0448/INT.2026.00422
Canonical	mdoi:110.0448/INT.2026.00422
Resolver URL	https://mdoi.org/110.0448/INT.2026.00422
Resource URL	Open resource
Document URL	Open document
Content Type	Article
Authors	Sinéad M. Mullin, Aidan J. Kelly, Méabh B. Ní Chathail, Suzanne Norris, Christopher E. Shannon, Helen M. Roche
Year	2025
Depositor	International Journal of Multidisciplinary Studies and Innovative Researchs Organisation
Prefix	110.0448
Registered	June 26, 2026
Updated	June 26, 2026
Status	Active
Visibility	Public

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Macronutrient Modulation in Metabolic Dysfunction-Associated Steatotic Liver Disease—the Molecular Role of Fatty Acids compared with Sugars in Human Metabolism and Disease Progression

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