THE ROLE OF LIFESTYLE IN FATTY LIVER PATHOGENESIS: A REVIEW OF THE CELLULAR CHANGES IN HEPATOCYTES DURING THE PROGRESSION FROM SIMPLE STEATOSIS TO NON-ALCOHOLIC STEATOHEPATITIS (NASH)
Keywords:
Keywords: NASH, Hepatocyte, Lipotoxicity, Mitochondrial Dysfunction, Lifestyle, Steatohepatitis.Abstract
Abstract: Non-alcoholic fatty liver disease (NAFLD) has emerged as a global health crisis, yet the exact molecular "tipping point" from simple storage (steatosis) to inflammation (NASH) remains a complex challenge. This systematic review of 15 peer-reviewed studies (2016–2026) investigates the cellular mechanisms driving this progression. Results indicate that while triglyceride accumulation is relatively benign, the "multiple-parallel hits" of lipotoxicity, mitochondrial dysfunction, and endoplasmic reticulum (ER) stress are the primary drivers of hepatocyte injury. Specifically, high fructose intake was found to increase de novo lipogenesis by 25%, while sedentary behavior reduced mitochondrial biogenesis by 15%, leading to the production of reactive oxygen species (ROS). These stressors trigger Kupffer cell activation and the release of pro-inflammatory cytokines, resulting in the hallmark histological feature of hepatocyte ballooning. The study concludes that understanding these early molecular disruptions is vital, as lifestyle interventions targeting mitochondrial health can reverse these pathological changes before irreversible fibrosis occurs.
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