The bioengineered tissue formed by iPSC-derived HLCs with an inducible knockdown expression of deacetylase sirtuin-1 (SIRT1), cultured in combination with macrophages, has been reported to mimic the pro-inflammatory phenotype upon lipid overloading and revealed the major implication of sirt1 in de novo lipogenesis and β-oxidation regulation, along with their pivotal role in NAFLD development and progression [92]. This evidence concerns the gene SIRT1 and metabolic dysfunction-associated steatotic liver disease.