TY - JOUR
T1 - Triglyceride lipases alter fuel metabolism and mitochondrial gene expression
AU - Watt, Matthew James
PY - 2009
Y1 - 2009
N2 - Fatty acids derived from the hydrolysis of adipose tissue and skeletal muscle triacylglycerol (TG) are an important energy substrate at rest and during prolonged moderate-intensity exercise. Hormone sensitive lipase (HSL) was long considered to be the rate-limiting enzyme for adipocyte and skeletal muscle TG lipolysis. However, the understanding of TG lipolysis regulation was recently challenged by the finding that adipose TG lipase (ATGL) is the predominant TG lipase in adipose tissue and an important regulator of TG degradation in skeletal muscle. Thus, it is now proposed that ATGL and HSL regulate lipolysis in a serial manner, with ATGL cleaving the first fatty acid and HSL the second fatty acid of TG. Further to this biochemical evaluation, the generation and metabolic characterization of ATGL-/- and HSL-/- mice have revealed distinct phenotypes. ATGL-/- mice are obese, exhibit impaired thermogenesis, oxidize more carbohydrate, and die prematurely due to cardiac dysfunction. Studies in HSL-/- mice report defective beta-adrenergic stimulated lipolysis, protection against high-fat diet-induced obesity, and possible impairments in insulin secretion. This review outlines the current understanding of the cellular regulation of TG lipases, lipolytic regulation, and the functional implications of manipulating ATGL and HSL in vivo.
AB - Fatty acids derived from the hydrolysis of adipose tissue and skeletal muscle triacylglycerol (TG) are an important energy substrate at rest and during prolonged moderate-intensity exercise. Hormone sensitive lipase (HSL) was long considered to be the rate-limiting enzyme for adipocyte and skeletal muscle TG lipolysis. However, the understanding of TG lipolysis regulation was recently challenged by the finding that adipose TG lipase (ATGL) is the predominant TG lipase in adipose tissue and an important regulator of TG degradation in skeletal muscle. Thus, it is now proposed that ATGL and HSL regulate lipolysis in a serial manner, with ATGL cleaving the first fatty acid and HSL the second fatty acid of TG. Further to this biochemical evaluation, the generation and metabolic characterization of ATGL-/- and HSL-/- mice have revealed distinct phenotypes. ATGL-/- mice are obese, exhibit impaired thermogenesis, oxidize more carbohydrate, and die prematurely due to cardiac dysfunction. Studies in HSL-/- mice report defective beta-adrenergic stimulated lipolysis, protection against high-fat diet-induced obesity, and possible impairments in insulin secretion. This review outlines the current understanding of the cellular regulation of TG lipases, lipolytic regulation, and the functional implications of manipulating ATGL and HSL in vivo.
UR - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=19448696
U2 - 10.1139/H09-019
DO - 10.1139/H09-019
M3 - Article
VL - 34
SP - 340
EP - 347
JO - Applied physiology, nutrition, and metabolism = Physiologie appliquee, nutrition et metabolisme
JF - Applied physiology, nutrition, and metabolism = Physiologie appliquee, nutrition et metabolisme
SN - 1715-5312
IS - 3
ER -