Moreover, overexpression of both NR1D1 and ApoA5 via AAV8 did not reverse severe hyperlipidemia and NASH in ApoA5-/- hamsters and fed an HFD (data not shown), raising a concern of gene therapy applied to patients with severe HTG due to ApoA5. This evidence concerns the gene NR1D1 and metabolic dysfunction-associated steatohepatitis.