Open Access

REVIEW

Obesity, Metabolic Dysfunction-Associated Steatotic Liver Disease and Hepatocellular Carcinoma: How Molecular Changes Impact Cellular Functions

Ralf Weiskirchen¹, Amedeo Lonardo^2,*

1 Institute of Molecular Pathobiochemistry, Experimental Gene Therapy, and Clinical Chemistry (IFMPEGKC), RWTH University Hospital Aachen, Pauwelsstr. 30, Aachen, D-52074, Germany
2 AOU Modena, Department of Internal Medicine, Ospedale Civile di Baggiovara (-2023), Modena, Italy

* Corresponding Author: Amedeo Lonardo. Email:

(This article belongs to the Special Issue: Molecular Insights into the Obesity-Cancer Nexus: From Cellular Mechanisms to Therapeutic Targets)

BIOCELL 2026, 50(5), 1 https://doi.org/10.32604/biocell.2026.076177

Received 15 November 2025; Accepted 19 January 2026; Issue published 13 May 2026

Abstract

Obesity is a complex chronic condition characterized by an excess of body fat that manifests in various clinical pathophenotypes, each affecting liver health differently. One significant cause of chronic liver diseases among those living with obesity is metabolic dysfunction-associated steatotic liver disease (MASLD), which is linked to one or more cardiometabolic risk factors in individuals who do not engage in harmful alcohol consumption. Hepatocellular carcinoma (HCC) is the most common form of primary liver cancer and is increasingly being associated with MASLD through intricate immunological, cellular, proinflammatory, molecular, and genetic mechanisms. In this review, we examine the molecular changes and altered functions of hepatocytes related to lipid accumulation, oxidative stress, inflammatory responses, and the regulation of signaling pathways such as mechanistic target of rapamycin (mTOR), AMP-activated protein kinase (AMPK), and nuclear factor kappa B (NF-κB). We also explore how these processes impact cell proliferation, apoptosis, autophagy, migration, the immunological environment, angiogenesis, and cell differentiation. Finally, we discuss the challenges posed by MASLD-HCC and how these may be effectively managed by promoting effective risk stratification, early diagnosis, and innovative treatment schedules for this numerically growing category of patients.

---

Graphic Abstract

---

Keywords

---