Adipose triglyceride lipase plays a key role in the supply of the working muscle with fatty acids.
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.
Schoiswohl
Gabriele
G
Institute of Molecular Biosciences, University of Graz, Graz, Austria.
Schweiger
Martina
M
Schreiber
Renate
R
Gorkiewicz
Gregor
G
Preiss-Landl
Karina
K
Taschler
Ulrike
U
Zierler
Kathrin A
KA
Radner
Franz P W
FP
Eichmann
Thomas O
TO
Kienesberger
Petra C
PC
Eder
Sandra
S
Lass
Achim
A
Haemmerle
Guenter
G
Alsted
Thomas J
TJ
Kiens
Bente
B
Hoefler
Gerald
G
Zechner
Rudolf
R
Zimmermann
Robert
R
D000818:Animals; D002241:Carbohydrates / Q000097:blood; D002265:Carboxylic Ester Hydrolases / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D004734:Energy Metabolism; D005227:Fatty Acids / Q000378:metabolism*; D005260:Female; D055786:Gene Knockout Techniques; D006003:Glycogen / Q000378:metabolism; D008049:Lipase; D008055:Lipids / Q000097:blood; D008099:Liver / Q000378:metabolism; D008124:Locomotion; D008297:Male; D051379:Mice; D009132:Muscles / Q000166:cytology / Q000378:metabolism* / Q000502:physiology; D009154:Mutation; D010805:Physical Conditioning, Animal; D012146:Rest; D000217:Acyltransferases
D002241:Carbohydrates; D002265:Carboxylic Ester Hydrolases; D005227:Fatty Acids; D006003:Glycogen; D008049:Lipase; D008055:Lipids; C494445:PNPLA2 protein, mouse; D000217:Acyltransferases