NR1H4 and obesity due to melanocortin 4 receptor deficiency: In fact, lipid polyunsaturation and the Alox5 pathway associate with obesity, insulin resistance and NAFLD.40 Altogether, we showed that simultaneous activation of PPARα and FXR robustly modulates hepatic lipid metabolism, resulting in a strong reduction in steatosis and cholesterol accumulation by decreasing fatty acid uptake in the liver, impairing metabolic pathways involved in fatty acid polyunsaturation, and re-establishing β-oxidation to basal levels.