While BALB/c mice are known to be completely refractory to fructose-induced activation of lipogenesis29, the overall discrepancies are potentially related to the lack of hormonal regulation in the ex vivo liver slice experimental system, and the lack of an integrated in vivo response, including absence of hyperglycaemia and hyperinsulinemia, with glucose and insulin well known to contribute to excessive lipid accumulation51. Here, INS is linked to hyperinsulinism.