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New insights into intravascular lipolysis and new causes of hypertriglyceridemia
Author(s) -
Young Stephen G.,
Beigneux Anne,
Fong Loren,
Ploug Michael
Publication year - 2017
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.31.1_supplement.527.2
Subject(s) - lipoprotein lipase , hypertriglyceridemia , lipolysis , chemistry , missense mutation , medicine , endocrinology , biochemistry , biology , enzyme , triglyceride , gene , mutation , adipose tissue , cholesterol
GPIHBP1, a GPI‐anchored protein of capillary endothelial cells, is crucial for the lipolytic processing of triglyceride‐rich lipoproteins (TRLs). GPIHBP1 binds lipoprotein lipase (LPL) in the interstitial spaces and shuttles the enzyme to its site of action in the capillary lumen. GPIHBP1 is also required for the margination of TRLs along capillaries—so that lipolytic processing can proceed. Finally, the binding of LPL to GPIHBP1 reduces the spontaneous unfolding of LPL's catalytic domain, thereby stabilizing LPL catalytic activity. GPIHBP1 mutations cause severe hypertriglyceridemia; the majority are missense mutations that interfere with the proper conformation of GPIHBP1's LU (Ly6‐uPAR) domain and thereby abolish the capacity of GPIHBP1 to bind and transport LPL. Recent studies have shown that GPIHBP1 is also highly to the pathogenesis of acquired forms of hypertriglyceridemia. Support or Funding Information Leducq Foundation; National Heart, Lung, and Blood Institute