Cellular cholesterol accumulation modulates high fat high sucrose (HFHS) diet-induced ER stress and hepatic inflammasome activation in the development of non-alcoholic steatohepatitis

Both dietary fat and cholesterol may independently promote liver fat accumulation and inflammation in non-alcoholic steatohepatitis.

• Accumulation of cholesterol in liver cells is associated with increased stress in the endoplasmic reticulum and activation of inflammation-related pathways.
• Mouse models with a high-fat, high-sugar (HFHS) diet show that cholesterol crystals form in the liver, correlating with increased endoplasmic reticulum cholesterol.
• Mice lacking specific cholesterol receptors appear protected from the stresses and inflammation associated with cholesterol accumulation.
• High cholesterol diets alone can induce liver fat buildup and inflammation independent of endoplasmic reticulum cholesterol levels.
• In vitro experiments indicate that increased cellular cholesterol plays a key role in triggering liver fat accumulation and inflammatory responses.

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