Alterations in the expression of genes related to fatty acid transport and oxidation in liver tissue are associated with protection against diet-induced liver steatosis by acid sphingomyelinase knockout. We used quantitative real-time polymerase chain reaction (qRT-PCR) to quantify RNA in liver tissue from acid sphingomyelinase–deficient (Smpd−/−) mice and C57BL/6 (wild-type, WT) mice fed a standard diet (SD) or a Western diet (WD). (A) Ndufa6 mRNA expression was not significantly different between Smpd−/− mice and WT mice irrespective of diet. (B) Expression of ATPase H+ transporting V0 subunit D1 (Atp6v0d1), a target of Rictor, whose activation was found to be altered, according to the results of quantitative proteome analysis, was slightly lower in SD-fed Smpd−/− mice than in SD-fed WT mice. WD consumption diminished Atp6v0d1 expression in Smpd−/− mice but increased its expression in WT mice; this difference was statistically significant. (C, D) The expression of Fabp4 (target gene of Ppara and Pparg) and Fabp5 (target gene of Rictor, Ppara, and Pparg) mRNA target genes was significantly higher in the liver of WD-fed Smpd−/− mice than in the liver of WD-fed WT mice. (E, F) In liver tissue samples from obese subjects (see Suppl. Table 3), mRNA expression of FABP4 and FABP5 was significantly higher in patients with maximal adipocyte size (≥125 μm).