Adipose triglyceride lipase deletion from adipocytes, but not skeletal myocytes, impairs acute exercise performance in mice

John J. Dubé, Mitch T. Sitnick, Gabriele Schoiswohl, Rachel C. Wills, Mahesh K. Basantani, Lingzhi Cai, Thomas Pulinilkunnil, Erin E. Kershaw

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

Adipose triglyceride lipase (ATGL) is the rate-limiting enzyme mediating triacylglycerol hydrolysis in virtually all cells, including adipocytes and skeletal myocytes, and hence, plays a critical role in mobilizing fatty acids. Global ATGL deficiency promotes skeletal myopathy and exercise intolerance in mice and humans, and yet the tissue-specific contributions to these phenotypes remain unknown. The goal of this study was to determine the relative contribution of ATGL-mediated triacylglycerol hydrolysis in adipocytes vs. skeletal myocytes to acute exercise performance. To achieve this goal, we generated murine models with adipocyte- and skeletal myocyte-specific targeted deletion of ATGL. We then subjected untrained mice to acute peak and submaximal exercise interventions and assessed exercise performance and energy substrate metabolism. Impaired ATGL-mediated lipolysis within adipocytes reduced peak and submaximal exercise performance, reduced peripheral energy substrate availability, shifted energy substrate preference toward carbohydrate oxidation, and decreased HSL Ser660 phosphorylation and mitochondrial respiration within skeletal muscle. In contrast, impaired ATGL-mediated lipolysis within skeletal myocytes was not sufficient to reduce peak and submaximal exercise performance or peripheral energy substrate availability and instead tended to enhance metabolic flexibility during peak exercise. Furthermore, the expanded intramyocellular triacylglycerol pool in these mice was reduced following exercise in association with preserved HSL phosphorylation, suggesting that HSL may compensate for impaired ATGL action in skeletal muscle during exercise. These data suggest that adipocyte rather than skeletal myocyte ATGL-mediated lipolysis plays a greater role during acute exercise in part because of compensatory mechanisms that maintain lipolysis in muscle, but not adipose tissue, when ATGL is absent.

Original languageEnglish
Pages (from-to)E879-E890
JournalAmerican Journal of Physiology - Endocrinology and Metabolism
Volume308
Issue number10
DOIs
StatePublished - 15 May 2015

Fingerprint

Skeletal Muscle Fibers
Lipase
Adipocytes
Exercise
Lipolysis
Triglycerides
Skeletal Muscle
Hydrolysis
Phosphorylation
Muscular Diseases
Energy Metabolism
Adipose Tissue
Respiration
Fatty Acids
Carbohydrates
Phenotype
Muscles
Enzymes

Keywords

  • Adipose triglyceride lipase
  • Exercise
  • Lipolysis

Cite this

Dubé, John J. ; Sitnick, Mitch T. ; Schoiswohl, Gabriele ; Wills, Rachel C. ; Basantani, Mahesh K. ; Cai, Lingzhi ; Pulinilkunnil, Thomas ; Kershaw, Erin E. / Adipose triglyceride lipase deletion from adipocytes, but not skeletal myocytes, impairs acute exercise performance in mice. In: American Journal of Physiology - Endocrinology and Metabolism. 2015 ; Vol. 308, No. 10. pp. E879-E890.
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Adipose triglyceride lipase deletion from adipocytes, but not skeletal myocytes, impairs acute exercise performance in mice. / Dubé, John J.; Sitnick, Mitch T.; Schoiswohl, Gabriele; Wills, Rachel C.; Basantani, Mahesh K.; Cai, Lingzhi; Pulinilkunnil, Thomas; Kershaw, Erin E.

In: American Journal of Physiology - Endocrinology and Metabolism, Vol. 308, No. 10, 15.05.2015, p. E879-E890.

Research output: Contribution to journalArticle

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AU - Dubé, John J.

AU - Sitnick, Mitch T.

AU - Schoiswohl, Gabriele

AU - Wills, Rachel C.

AU - Basantani, Mahesh K.

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AU - Kershaw, Erin E.

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