title: Effect of Global ATGL Knockout on Murine Fasting Glucose Kinetics.
abstract: 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-(13)C6]glucose followed by LC-MS/MS targeted mass-isotopomer analysis of blood glucose. EGP was quantified by isotope dilution of [U-(13)C6]glucose while Cori cycling was estimated by analysis of glucose triose (13)C-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 μmol/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 (13)C-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.
authors.affiliation: CNC-Center for Neuroscience and Cell Biology, University of Coimbra, Coimbra, Portugal.
authors.forename: Margarida
authors.initials: M
authors.lastname: Coelho
authors.affiliation: MRC National Institute for Medical Research, London, UK.
authors.forename: Patricia
authors.initials: P
authors.lastname: Nunes
authors.affiliation: CNC-Center for Neuroscience and Cell Biology, University of Coimbra, Coimbra, Portugal.
authors.forename: Vera M
authors.initials: VM
authors.lastname: Mendes
authors.affiliation: CNC-Center for Neuroscience and Cell Biology, University of Coimbra, Coimbra, Portugal.
authors.forename: Bruno
authors.initials: B
authors.lastname: Manadas
authors.affiliation: Department of Radiology, Radboud University Nijmegen Medical Centre, Nijmegen, Netherlands.
authors.forename: Arend
authors.initials: A
authors.lastname: Heerschap
authors.affiliation: CNC-Center for Neuroscience and Cell Biology, University of Coimbra, Coimbra, Portugal ; Portuguese Diabetes Association (APDP), Lisbon, Portugal.
authors.forename: John G
authors.initials: JG
authors.lastname: Jones
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000378:metabolism*; D002247:Carbon Isotopes; D002853:Chromatography, Liquid; D002952:Citric Acid Cycle; D005230:Fatty Acids, Nonesterified / Q000378:metabolism*; D008049:Lipase / Q000235:genetics*; D008099:Liver / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D010084:Oxidation-Reduction; D066244:Proton Magnetic Resonance Spectroscopy; D053719:Tandem Mass Spectrometry; D000217:Acyltransferases
chemical_list: D001786:Blood Glucose; D002247:Carbon Isotopes; D005230:Fatty Acids, Nonesterified; D008049:Lipase; C494445:PNPLA2 protein, mouse; D000217:Acyltransferases