Premium
Adipose triglyceride lipase (ATGL) deletion from adipocytes, but not skeletal myocytes, impairs acute exercise performance in mice
Author(s) -
Sitnick Mitchell,
Dube John,
Schoiswohl Gabriele,
Kershaw Erin
Publication year - 2015
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.29.1_supplement.675.16
Subject(s) - adipose triglyceride lipase , lipolysis , medicine , endocrinology , skeletal muscle , adipocyte , adipose tissue , triglyceride , chemistry , lipid droplet , myocyte , biology , cholesterol
Fatty acids (FA) and glucose are essential energy substrates that supply exercising muscle. While the selection of substrates is highly influenced by their availability and the intensity and duration of exercise, for prolonged exercise FA are the key substrate. Adipose Triglyceride Lipase (ATGL) is the rate‐limiting enzyme mediating intracellular triacylglycerol hydrolysis and should play a key role in the mobilization of FA during exercise. However, the contribution of adipose versus skeletal muscle fatty acid mobilization to support exercise remains unclear. To gain insight, we generated adipocyte or skeletal myocyte‐specific ATGL knockout mice and determined their response to acute peak and submaximal exercise. We found that adipocyte ATGL‐mediated lipolysis was crucial to support exercise performance, likely owing to limited FA availability and reliance on a rapidly depleted carbohydrate store. Impaired skeletal muscle ATGL‐mediated lipolysis did not impact exercise tolerance and these mice exhibited improved metabolic flexibility during peak exercise. This suggests that adipocyte rather than skeletal myocyte ATGL‐mediated lipolysis plays a greater role during acute peak and submaximal endurance exercise due to limits in substrate availability and greater reliance on carbohydrate oxidation. While further investigation is needed, this suggests the role of IMCL is more of a stop‐gap substrate store to bridge carbohydrate use and FA mobilization and delivery from adipocytes to working muscle. Supported by NIH R01DK090166, HHMI Physician‐Scientist Early Career Award; NIH T32 DK007052