Effect of Global ATGL Knockout on Murine Fasting Glucose Kinetics

Mice deficient in adipose triglyceride lipase (atgl-/-) present elevated ectopic lipid levels but are paradoxically glucose-tolerant. measurement of endogenous glucose production (egp) and cori cycle activity provide insights into the maintenance of glycemic control in these animals. these parameters were determined in 7 wild-type (atgl-/-) and 6 atgl-/- mice by a primed-infusion of [u-13c6]glucose followed by lc-ms/ms targeted mass-isotopomer analysis of blood glucose. egp was quantified by isotope dilution of [u-13c6]glucose while cori cycling was estimated by analysis of glucose triose 13c-isotopomers. fasting plasma free fatty-acids were significantly lower in atgl-/- versus control mice (0.43 ± 0.05 mm versus 0.73 ± 0.11 mm,p<0.05). six-hour fasting egp rates were identical for both atgl-/- and control mice (79 ± 11 versus 71 ± 7 mol/kg/min,resp.). peripheral glucose metabolism was dominated by cori cycling (80 ± 2% and 82 ± 7% of glucose disposal for atgl-/- and control mice,resp.) indicating that peripheral glucose oxidation was not significantly upregulated in atgl-/- mice under these conditions. the glucose 13c-isotopomer distributions in both atgl-/- and control mice were consistent with extensive hepatic pyruvate recycling. this suggests that gluconeogenic outflow from the krebs cycle was also well compensated in atgl-/- mice. copyright © 2015 margarida coelho et al.