Gluconeogenesis in perfused livers of genetically obese-hyperglycemic (ob/ob) mice

Hypertrophy of liver cells, as measured by decreased mg DNA per g wet liver, from obese mice (C57BL/6J ob/ob) was associated with a marked increase in triacylglycerol content per g wet liver when compared with control lean mice (C57BL/6J ?/+). The difference between the rates of net glucose production from lactate in isolated perfused livers from obese and lean mice was small when expressed per g wet liver. However, calculation of these rates either on a DNA or body weight basis indicated that the rate of gluconeogenesis in livers from obese mice was twice that of lean mice. Using perfused livers from lean mice, the ratio of net uptake of C3-substrate to gluconeogenesis indicated that a major proportion of lactate disappearing from the perfusion medium could not be accounted for in the appearance of glucose; but using the perfused livers of obese mice, almost all of the net lactate disappearance could be accounted for by a net increase in glucose production.