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

Abstract

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. Keywords: MASLD, MASH, inflammation, fibrosis, fatty acids, carbohydrates, sugars, fiber, dietary intervention, precision nutrition