The decrease in PPARα targets in both long-term HFD-fed Fsp27−/− mice (23) and ASO-treated mice (herein) suggest that a combination of ASO plus a PPARα synthetic agonist might be necessary to stimulate the efficient mobilization and oxidation of hepatic lipids, and to provide therapeutic reduction of hepatic steatosis. The gene discussed is PPARA; the disease is fatty liver disease.