title: Skeletal muscle triacylglycerol hydrolysis does not influence metabolic complications of obesity.
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.
authors.affiliation: Division of Endocrinology, Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania.
authors.forename: Mitch T
authors.initials: MT
authors.lastname: Sitnick
authors.forename: Mahesh K
authors.initials: MK
authors.lastname: Basantani
authors.forename: Lingzhi
authors.initials: L
authors.lastname: Cai
authors.forename: Gabriele
authors.initials: G
authors.lastname: Schoiswohl
authors.forename: Cynthia F
authors.initials: CF
authors.lastname: Yazbeck
authors.forename: Giovanna
authors.initials: G
authors.lastname: Distefano
authors.forename: Vladimir
authors.initials: V
authors.lastname: Ritov
authors.forename: James P
authors.initials: JP
authors.lastname: DeLany
authors.forename: Renate
authors.initials: R
authors.lastname: Schreiber
authors.forename: Donna B
authors.initials: DB
authors.lastname: Stolz
authors.forename: Noah P
authors.initials: NP
authors.lastname: Gardner
authors.forename: Petra C
authors.initials: PC
authors.lastname: Kienesberger
authors.forename: Thomas
authors.initials: T
authors.lastname: Pulinilkunnil
authors.forename: Rudolf
authors.initials: R
authors.lastname: Zechner
authors.forename: Bret H
authors.initials: BH
authors.lastname: Goodpaster
authors.forename: Paul
authors.initials: P
authors.lastname: Coen
authors.forename: Erin E
authors.initials: EE
authors.lastname: Kershaw
mesh_terms: D000273:Adipose Tissue / Q000378:metabolism*; D000818:Animals; D059305:Diet, High-Fat; D004734:Energy Metabolism; D006706:Homeostasis; D006868:Hydrolysis; D007333:Insulin Resistance / Q000502:physiology; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism*; D050356:Lipid Metabolism; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D018482:Muscle, Skeletal / Q000378:metabolism*; D009765:Obesity / Q000378:metabolism*; D010641:Phenotype; D010766:Phosphorylation; D014280:Triglycerides / Q000378:metabolism*
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; D014280:Triglycerides