Hormonal
Progression from simple steatosis to steatohepatitis (NASH) is driven by a 'second hit' involving oxidative stress, inflammation, and mitochondrial dysfunction, often triggered by excess free fatty acids.
Preventing progression to NASH requires reducing the metabolic load on the liver. This involves minimizing factors that cause oxidative stress and inflammation, such as excessive alcohol intake (though NAFLD is non-alcoholic, alcohol adds stress) and high sugar/fructose intake which drives de novo lipogenesis.
Day et al launched the 'two-hit-theory', stating that two succeeding wallops have to be delivered to the liver to cause NASH... The surplus of FFA within the liver causes the formation of excess amounts of ROS... This will trigger the inflammatory response and apoptosis as well activation of stellate cells.
Why this rating
Based on the review of multiple studies supporting the two-hit theory and oxidative stress mechanisms.
Source
Nonalcoholic fatty liver disease: An overview of current insights in pathogenesis, diagnosis and treatment
T.C.M.A. Schreuder et al. · World Journal of Gastroenterology · 2008
DOI 10.3748/wjg.14.2474
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- Insulin resistance drives hepatic steatosis by disrupting normal insulin signaling, leading to unchecked de novo lipogenesis and increased free fatty acid flux from visceral adipose tissue.Good
- Adipose tissue acts as an endocrine organ in obesity, secreting inflammatory cytokines (like TNF-alpha) and adipokines (like RBP4) that induce insulin resistance in the liver and muscle.Good
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