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Mechanistically, this is commonly mediated by the prevalent two-hit hypothesis that implies accumulation of TG in hepatocytes (steatosis) in the first hit, followed by triggering progression to inflammation, oxidative stress, and apoptosis in the second hit ( Smoking Exacerbates Effects of Dietary Fat on Liver Animal experiments using first-hand (delivered via a smoking device designed to puff the smoke into the inhalation chamber housing the animals), second-hand smoke (side-stream whole smoke solution delivered via a puffer box), or nicotine and models of genetic or diet-induced obesity (DIO) provide perhaps the strongest evidence linking nicotine to hepatic steatosis and NAFLD