Using three models of HSL deficiency (systemic, hepatic and adipose) we show that, surprisingly, unlike ATGL, liver fat levels are unrelated to liver HSL but that adipose HSL deficiency alone is sufficient to produce a similar level of hepatic steatosis as in systemic HSL deficiency. This evidence concerns the gene PNPLA2 and hyperinsulinemic hypoglycemia, familial, 4.