In conclusion, our work provides the first evidence that AMPK-mediated mitochondrial biogenesis and the Nrf2 pathway are involved in acute hyperlipidemia-induced liver and heart impairments and shows that HAE exerts protective effects on hyperlipidemia-related metabolic disorders and tissue impairments by upregulating the AMPK/PGC-1α/Nrf2 cascade. Here, PPARGC1A is linked to Other metabolic disease.