In response to the intervention of nicotine, ceramide, a lipotoxic lipid, is produced extensively in the intestine by phosphorylating AMPKα1 and SMPD3 S208/209, which may impede the degradation of SMPD3 and the progression of MASLD [86,142]. The gene discussed is PRKAA1; the disease is metabolic dysfunction-associated steatotic liver disease.