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

Ulrike Taschler,Achim Lass,Robert Zimmermann,Gerald Hoefler,Kathrin A Zierler,Thomas O Eichmann,Franz P.W Radner,Martina Schweiger,Guenter Haemmerle,Thomas J Alsted,Sandra Eder,Renate Schreiber,Karina Preiss-Landl,Gregor Gorkiewicz,Bente Kiens,Petra C Kienesberger,Gabriele Schoiswohl,Rudolf Zechner

doi:10.1194/jlr.m001073

Abstract

FAs are mobilized from triglyceride (TG) stores during exercise to supply the working muscle with energy. Mice deficient for adipose triglyceride lipase (ATGL-ko) 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. Because 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.

Highlights

FAs are mobilized from triglyceride (TG) stores during exercise to supply the working muscle with energy
Our observations strongly indicate that the lack of Adipose triglyceride lipase (ATGL) in adipose tissue leads to an undersupply of the muscle with FA, which is compensated by an increased use of carbohydrates for energy conversion
The present study demonstrates that mice lacking ATGL cannot adjust circulating FA levels to the increased energy consumption of the body during exercise

Summary

Introduction

FAs are mobilized from triglyceride (TG) stores during exercise to supply the working muscle with energy. Mice deficient for adipose triglyceride lipase (ATGL-ko) exhibit defective lipolysis and accumulate TG in adipose tissue and muscle, suggesting that ATGL deficiency affects energy availability and substrate utilization in working muscle. 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. Most of the body’s energy reserves are stored in white adipose tissue (WAT) implicating that the supply of the muscle with energy during prolonged exercise is largely dependent on adipose lipolysis. In the absence of both enzymes, hormone-induced FA release in WAT is decreased by more than 95% [9] Together, these observations suggest that efficient lipolysis is dependent on the coordinate action of.

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