We conclude that in the absence of PPARα, a vicious cycle pertaining to the (i) lower mitochondria numbers, (ii) mitochondrial dysfunctions, (iii) impaired mitochondrial FA β-oxidation, (iii) hypoketonemia either due to a lack of direct PPARα stimulation of Hmgcs2 or a lack of essential co-factors provided by functional FAO, (iv) lack of epigenetic activation of FGF21 by ketone bodies (e.g., β-hydroxybutyrate), and (v) a surge in nutritional lipids upon milk suckling, exists to concomitantly contribute to the development of hepatic steatosis in neonates (Figure 8C). The gene discussed is HMGCS2; the disease is Hepatic steatosis.