To shed light on the underlying molecular mechanisms, we present here novel data showing that empagliflozin treatment for five weeks in HFD-fed ApoE(-/-) mice not only decreases fasting glucose, total cholesterol and triglycerides serum levels, but also improves the underlying NAFLD histological features by activating autophagy, alleviating ER stress, and attenuating apoptosis. The gene discussed is APOE; the disease is metabolic dysfunction-associated steatotic liver disease.