Hepatic Insulin Resistance and Steatosis in Metabolic Dysfunction-Associated Steatotic Liver Disease: New Insights into Mechanisms and Clinical Implications.
Level 5 - mechanism / opinion, no new human data
Narrative review of mechanisms with no systematic search methodology or original clinical data.
PubMed 40935652 · doi:10.4093/dmj.2025.0644
What was done
This narrative review examined the molecular and metabolic mechanisms connecting hepatic insulin resistance, substrate-driven de novo lipogenesis, free fatty acid flux, and lipotoxic intermediates (such as diacylglycerols and ceramides) to the progression of metabolic dysfunction-associated steatotic liver disease (MASLD), alongside an overview of clinical implications and emerging pharmacotherapies.
What was found
The abstract reports no numerical findings or statistical estimates. It qualitatively describes how de novo lipogenesis and adipose lipolysis drive hepatic triglyceride storage and lipotoxicity, outlines the roles of mTORC1, protein kinase C, and zonal insulin signaling in selective hepatic insulin resistance, and notes emerging pharmacologic agents (such as resmetirom) alongside lifestyle modification.
Why it matters
It provides an updated mechanistic framework for how substrate overload and selective insulin signaling pathways sustain liver steatosis, highlighting potential molecular targets for MASLD therapies.
Limits
The paper is a narrative review without systematic search criteria, predefined study selection protocols, or primary experimental data, and the abstract provides no quantitative effect sizes or clinical trial outcome metrics.
Cited by
- supports Accumulation of fat in the liver interferes with insulin action, leading to insulin resistance.