Adipose Tissue Browning in MASLD and Its Molecular Mechanisms and Metabolic Crosstalk

Abstract

PURPOSE OF REVIEW: Metabolic dysfunction-associated steatotic liver disease (MASLD) is an increasingly prevalent complication of obesity and metabolic dysregulation, with limited therapies targeting upstream drivers of disease. Adipose tissue has emerged as a central regulator of systemic metabolic homeostasis, where dysfunction contributes to excess free fatty acid flux, chronic inflammation, and hepatic steatosis. In this context, adipose tissue browning-the induction of thermogenically active beige adipocytes within white adipose depots-has gained attention as a potential therapeutic mechanism. RECENT FINDINGS: Recent advances highlight that adipose browning modulates multiple pathways relevant to MASLD. These include enhanced mitochondrial β-oxidation and energy expenditure, leading to reduced lipid delivery to the liver, as well as endocrine signaling mediated by batokines such as fibroblast growth factor 21 (FGF21), irisin, and neuregulin 4 (Nrg4). Collectively, these pathways influence hepatic lipid metabolism, insulin sensitivity, and inflammatory and fibrotic processes. The preclinical studies consistently demonstrate metabolic and hepatoprotective benefits of browning; however, translational evidence in humans remains limited and heterogeneous. Factors such as reduced thermogenic capacity in obesity, inter-individual variability, and challenges in sustaining browning activation constrain clinical applicability. Overall, adipose tissue browning represents a promising component of a systems-based approach to MASLD. Future work should focus on integrating mechanistic insights with clinical investigation to clarify its therapeutic potential and to identify strategies that enable durable and patient-specific metabolic benefits.