Physiological regulation of lipoprotein lipase.
The enzyme lipoprotein lipase (LPL), originally identified as the clearing factor lipase, hydrolyzes triglycerides present in the triglyceride-rich lipoproteins VLDL and chylomicrons. LPL is primarily expressed in tissues that oxidize or store fatty acids in large quantities such as the heart, skeletal muscle, brown adipose tissue and white adipose tissue. Upon production by the underlying parenchymal cells, LPL is transported and attached to the capillary endothelium by the protein GPIHBP1. Because LPL is rate limiting for plasma triglyceride clearance and tissue uptake of fatty acids, the activity of LPL is carefully controlled to adjust fatty acid uptake to the requirements of the underlying tissue via multiple mechanisms at the transcriptional and post-translational level. Although various stimuli influence LPL gene transcription, it is now evident that most of the physiological variation in LPL activity, such as during fasting and exercise, appears to be driven via post-translational mechanisms by extracellular proteins. These proteins can be divided into two main groups: the liver-derived apolipoproteins APOC1, APOC2, APOC3, APOA5, and APOE, and the angiopoietin-like proteins ANGPTL3, ANGPTL4 and ANGPTL8, which have a broader expression profile. This review will summarize the available literature on the regulation of LPL activity in various tissues, with an emphasis on the response to diverse physiological stimuli.
Nutrition, Metabolism and Genomics Group, Division of Human Nutrition, Wageningen University, Bomenweg 2, 6703HD Wageningen, The Netherlands.
Sander
S
Kersten
D000273:Adipose Tissue / Q000502:physiology; D042682:Angiopoietins / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D001053:Apolipoproteins / Q000235:genetics / Q000378:metabolism*; D002914:Chylomicrons / Q000378:metabolism; D005786:Gene Expression Regulation; D006321:Heart / Q000502:physiology; D006801:Humans; D008071:Lipoprotein Lipase / Q000235:genetics / Q000378:metabolism*; D008079:Lipoproteins, VLDL / Q000378:metabolism; D008099:Liver / Q000502:physiology; D018482:Muscle, Skeletal / Q000502:physiology; D015398:Signal Transduction; D014158:Transcription, Genetic; D014280:Triglycerides / Q000378:metabolism
D042682:Angiopoietins; D001053:Apolipoproteins; D002914:Chylomicrons; D008079:Lipoproteins, VLDL; D014280:Triglycerides; D008071:Lipoprotein Lipase
Adipose tissue; Angiopoietin-like proteins; Apolipoproteins; Lipoprotein lipase; Muscle; Triglyceride-rich lipoproteins