Immune metabolic reprogramming in MASLD.

Metabolic dysfunction-associated steatotic liver disease (MASLD) is a major global health challenge driven by the interplay between metabolic dysregulation and chronic low-grade inflammation. Beyond simple hepatic lipid accumulation, MASLD is characterized by extensive remodeling of the liver immune microenvironment in response to metabolic stress and persistent immunological activation. Recent advances in the field of immunometabolism have revealed that metabolic pathways not only shape immune cell identity and functions, but are also themselves influenced by immune responses, creating a reciprocal circuit that drives hepatic and systemic metabolism dysfunction. In this review, we examine how innate and adaptive immune cells, with an extensive focus on macrophages, undergo metabolic reprogramming during MASLD progression, and how these changes contribute to inflammation, fibrosis, and tissue injury. We also discuss how the hepatic immune niche is reshaped by the spatial distribution of parenchymal cells to promote disease progression. Finally, we highlight emerging therapeutic strategies targeting immunometabolic pathways, which hold promise for restoring liver homeostasis and preventing the progression of MASLD.