Key result
MASLD drives systemic cardio-renal-hepatic dysfunction via altered BDNF and NGF hepatokine signaling.
Why the study?
To evaluate liver, heart, and kidney crosstalk in MASLD and MASH, highlighting non-traditional hepatokines, shared therapeutic targets, and molecular mechanisms driving cardiorenal complications.
MASLD acts as a systemic driver of multi-organ dysfunction within the cardio-renal-hepatic axis, highlighting specific hepatokine signatures as potential therapeutic targets and biomarkers.
Supports hepatokine-targeted research in MASLD; should not yet change cardiorenal management.
Purpose of Review To evaluate the crosstalk between the liver, heart, and kidneys in metabolic dysfunction-associated steatotic liver disease (MASLD) and metabolic dysfunction-associated steatohepatitis (MASH), highlighting the distinct regulatory roles of non-traditional hepatokines, and to assess shared therapeutic targets and molecular mechanisms driving cardiorenal complications in MASLD patients. Recent Findings Emerging evidence highlights that hepatic lipid accumulation drives cardiac damage, which manifests as adverse remodeling, diastolic dysfunction, and coronary microvascular dysfunction. These abnormalities are mediated primarily by systemic lipotoxicity, inflammation of epicardial adipose tissue, and a pro-thrombotic environment. Mechanistically, altered hepatokine signaling mediates systemic cross-talk. Specifically, the downregulation of cardioprotective and renoprotective brain-derived neurotrophic factor (BDNF) and the dual metabolic roles of nerve growth factor (NGF), fibroblast growth factor (FGF) 19, and FGF21 accelerate the progression of both heart failure and chronic kidney disease (CKD). Concurrently, metabolic therapies such as glucagon-like peptide-1 (GLP-1) receptor agonists, sodium-glucose cotransporter-2 (SGLT2) inhibitors, and peroxisome proliferator-activated receptor (PPAR) agonists demonstrate significant efficacy in ameliorating steatosis, inflammation, and overall metabolic outcomes. Summary MASLD acts as a systemic driver of multi-organ dysfunction within the cardio-renal-hepatic axis. Profiling specific hepatokine signatures offers a promising frontier for identifying novel therapeutic targets and biomarkers of disease acceleration. Furthermore, while current metabolic therapies show remarkable potential, rigorous clinical testing remains critical to definitively determine whether their cardiovascular and renal benefits stem from direct tissue-specific protective mechanisms or secondary metabolic improvements.
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Taylor et al. (2026) conducted a review in Metabolic dysfunction-associated steatotic liver disease (MASLD). MASLD acts as a systemic driver of multi-organ dysfunction within the cardio-renal-hepatic axis, mediated by altered hepatokine signaling such as BDNF and NGF.
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