TY - JOUR

T1 - Adipose triglyceride lipase plays a key role in the supply of the working muscle with fatty acids

AU - Schoiswohl, Gabriele

AU - Schweiger, Martina

AU - Schreiber, Renate

AU - Gorkiewicz, Gregor

AU - Preiss-Landl, Karina

AU - Taschler, Ulrike

AU - Zierler, Kathrin A.

AU - Radner, Franz P. W.

AU - Eichmann, Thomas O.

AU - Kienesberger, Petra C

AU - Eder, Sandra

AU - Lass, Achim

AU - Haemmerle, Guenter

AU - Alsted, Thomas Junker

AU - Kiens, Bente

AU - Hoefler, Gerald

AU - Zechner, Rudolf

AU - Zimmermann, Robert

N1 - CURIS 2010 5200 012

PY - 2010

Y1 - 2010

N2 - Fatty acids (FA) are mobilized from triglyceride (TG) stores during exercise to supply the working muscle with energy. Mice deficient for adipose triglyceride lipase (ATGLko)exhibit defective lipolysis and accumulate TG in adipose tissue and muscle suggesting that ATGL deficiency affects energy availability and substrate utilization in working muscle. In this study, we investigated the effect of moderate treadmill exercise on blood energy metabolites and liver glycogen stores in mice lacking ATGL. Since ATGL-ko mice exhibit massive accumulation of TG in the heart and cardiomyopathy, we also investigated a mouse model lacking ATGL in all tissues except cardiac muscle (ATGL-ko/CM). In contrast to ATGL-ko mice, these mice did not accumulate TG in the heart and had normal life expectancy. Exercise experiments revealed that ATGL-ko and ATGL-ko/CM mice are unable to increase circulating FA levels during exercise. The reduced availability of FA for energy conversion led to rapid depletion of liver glycogen stores and hypoglycemia. Together, our studies suggest that ATGL-ko mice cannot adjust circulating FA levels to the increased energy requirements of the working muscle resulting in an increased use of carbohydrates for energy conversion. Thus, ATGL activity is required for proper energy supply of the skeletal muscle during exercise.

AB - Fatty acids (FA) are mobilized from triglyceride (TG) stores during exercise to supply the working muscle with energy. Mice deficient for adipose triglyceride lipase (ATGLko)exhibit defective lipolysis and accumulate TG in adipose tissue and muscle suggesting that ATGL deficiency affects energy availability and substrate utilization in working muscle. In this study, we investigated the effect of moderate treadmill exercise on blood energy metabolites and liver glycogen stores in mice lacking ATGL. Since ATGL-ko mice exhibit massive accumulation of TG in the heart and cardiomyopathy, we also investigated a mouse model lacking ATGL in all tissues except cardiac muscle (ATGL-ko/CM). In contrast to ATGL-ko mice, these mice did not accumulate TG in the heart and had normal life expectancy. Exercise experiments revealed that ATGL-ko and ATGL-ko/CM mice are unable to increase circulating FA levels during exercise. The reduced availability of FA for energy conversion led to rapid depletion of liver glycogen stores and hypoglycemia. Together, our studies suggest that ATGL-ko mice cannot adjust circulating FA levels to the increased energy requirements of the working muscle resulting in an increased use of carbohydrates for energy conversion. Thus, ATGL activity is required for proper energy supply of the skeletal muscle during exercise.

U2 - 10.1194/jlr.M001073

DO - 10.1194/jlr.M001073

M3 - Journal article

C2 - 19965578

VL - 51

SP - 490

EP - 499

JO - Journal of Lipid Research

JF - Journal of Lipid Research

SN - 0022-2275

IS - 3

ER -