Sitnick 2013 Diabetes
|Sitnick MT, Basantani MK, Cai L, Schoiswohl G, Yazbeck CF, Distefano G, Ritov V, Delany JP, Schreiber R, Stolz DB, Gardner NP, Kienesberger PC, Pulinilkunnil T, Zechner R, Goodpaster BH, Coen P, Kershaw EE (2013) Skeletal muscle triacylglycerol hydrolysis does not influence metabolic complications of obesity. Diabetes 62:3350-6.|
Sitnick MT, Basantani MK, Cai L, Schoiswohl G, Yazbeck CF, Distefano G, Ritov V, Delany JP, Schreiber R, Stolz DB, Gardner NP, Kienesberger PC, Pulinilkunnil T, Zechner R, Goodpaster BH, Coen PM, Kershaw EE (2013) Diabetes
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 animal models with decreased (skeletal muscle-specific ATGL knockout or SMAKO mice) and increased (Ckm-ATGL transgenic mice) ATGL action exclusively in skeletal muscle. Despite dramatic changes in IMTG content on both chow and high-fat diet, 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 obesity.
• Keywords: Insulin resistance
Labels: MiParea: Respiration, Genetic knockout;overexpression, Exercise physiology;nutrition;life style Pathology: Diabetes, Obesity
Organism: Mouse Tissue;cell: Skeletal muscle