Skeletal muscle triacylglycerol hydrolysis does not influence metabolic complications of obesity

Mitch T. Sitnick, Mahesh K. Basantani, Lingzhi Cai, Gabriele Schoiswohl, Cynthia F. Yazbeck, Giovanna Distefano, Vladimir Ritov, James P. DeLany, Renate Schreiber, Donna B. Stolz, Noah P. Gardner, Petra C. Kienesberger, Thomas Pulinilkunnil, Rudolf Zechner, Bret H. Goodpaster, Paul Coen, Erin E. Kershaw

Research output: Contribution to journalArticle

36 Scopus citations

Abstract

Intramyocellular triacylglycerol (IMTG) accumulation is highly associated with insulin resistance and metabolic complications of obesity (lipotoxicity), whereas comparable IMTG accumulation in endurance-trained athletes is associated with insulin sensitivity (the athlete's paradox). Despite these findings, it remains unclear whether changes in IMTG accumulation and metabolism per se influence muscle-specific and systemic metabolic homeostasis and insulin responsiveness. By mediating the rate-limiting step in triacylglycerol hydrolysis, adipose triglyceride lipase (ATGL) has been proposed to influence the storage/production of deleterious as well as essential lipid metabolites. However, the physiological relevance of ATGL-mediated triacylglycerol hydrolysis in skeletal muscle remains unknown. To determine the contribution of IMTG hydrolysis to tissue-specific and systemic metabolic phenotypes in the context of obesity, we generated mice with targeted deletion or transgenic overexpression of ATGL exclusively in skeletal muscle. Despite dramatic changes in IMTG content on both chow and high-fat diets, modulation of ATGL-mediated IMTG hydrolysis did not significantly influence systemic energy, lipid, or glucose homeostasis, nor did it influence insulin responsiveness or mitochondrial function. These data argue against a role for altered IMTG accumulation and lipolysis in muscle insulin resistance and metabolic complications of obesity.

Original languageEnglish
Pages (from-to)3350-3361
Number of pages12
JournalDiabetes
Volume62
Issue number10
DOIs
StatePublished - 1 Oct 2013

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    Sitnick, M. T., Basantani, M. K., Cai, L., Schoiswohl, G., Yazbeck, C. F., Distefano, G., Ritov, V., DeLany, J. P., Schreiber, R., Stolz, D. B., Gardner, N. P., Kienesberger, P. C., Pulinilkunnil, T., Zechner, R., Goodpaster, B. H., Coen, P., & Kershaw, E. E. (2013). Skeletal muscle triacylglycerol hydrolysis does not influence metabolic complications of obesity. Diabetes, 62(10), 3350-3361. https://doi.org/10.2337/db13-0500