Molecular and Genetic Basis of Hormonal Signaling and Inter-Organ Crosstalk in Steatotic Liver Disease

Dear Colleagues,

Steatotic liver disease (SLD), which includes metabolic dysfunction-associated steatotic liver disease (MASLD) and alcohol-associated liver disease (ALD), represents a critical and growing global health challenge. These conditions often progress from simple steatosis to more severe forms, including steatohepatitis, advanced fibrosis, and cirrhosis. MASLD, in particular, is inextricably linked to obesity, insulin resistance, and impaired energy homeostasis—factors that collectively drive hepatic lipid accumulation and chronic inflammation.

The liver does not function in isolation; it is a central hub in a dynamic biological network, engaging in constant communication with the pancreas, adipose tissue, gut, and brain. Metabolic hormones and nutrient-derived signals serve as the primary mediators of this inter-organ crosstalk. Current research highlights that dysregulation in these hormonal pathways—such as the gut–liver–brain axis or adipokine signaling—is a key driver of disease progression. Furthermore, genetic predispositions and molecular shifts in hormonal receptor sensitivity offer significant insights into the heterogeneous nature of these disorders.

This Special Issue of Biomolecules aims to explore the molecular and genetic mechanisms underlying hormonal signaling and inter-organ communication in liver disease. We seek contributions that advance our understanding of how these dysregulated pathways influence hepatic fat accumulation, inflammation, and fibrosis, and how these insights can be leveraged for therapeutic innovation and precision medicine.

We welcome original research (basic, pre-clinical, or clinical), case reports, and comprehensive reviews. Research areas may include (but are not limited to) the following topics:

1. Hormonal regulation of glucose and lipid metabolism in the context of SLD.
2. The gut–liver axis, and specifically the role of incretin hormones and the molecular influence of the microbiome.
3. Adipose–liver crosstalk, mediated by adipokines, inflammatory cytokines, and lipid-derived signals.
4. Neuroendocrine control of hepatic energy homeostasis and the brain–liver–gut axis.
5. Genetic and epigenetic markers; influence on hormonal sensitivity and individual susceptibility to SLD progression.
6. Extracellular vesicles (EVs), and their role as mediators of inter-organ communication through the transport of bioactive cargo, including proteins, lipids, and non-coding RNAs, in the pathogenesis of liver disease.
7. Translational therapeutics: novel molecular targets (e.g., GLP-1/GIP dual agonists) and gene-based therapy approaches.

Dr. Karuna Rasineni
Guest Editor

Dr. Sundararajan Mahalingam
Guest Editor Assistant

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