Effect of Global ATGL Knockout on Murine Fasting Glucose Kinetics

• Autor(a) principal: Coelho, Margarida
• Data de Publicação: 2015
• Outros Autores: Nunes, Patricia, Mendes, Vera M., Manadas, Bruno, Heerschap, Arend, Jones, John G.
• Tipo de documento: Artigo
• Idioma: eng
• Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
• DOI: 10.1155/2015/542029
• Texto Completo: http://hdl.handle.net/10316/109183; https://doi.org/10.1155/2015/542029
• topic: Animals; Blood Glucose; Carbon Isotopes; Chromatography, Liquid; Fatty Acids, Nonesterified; Lipase; Liver; Mice; Mice, Knockout; Oxidation-Reduction; Proton Magnetic Resonance Spectroscopy; Tandem Mass Spectrometry; Citric Acid Cycle

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.