RT Journal Article
T1 Decreased GPIHBP1 protein levels in visceral adipose tissue partly underlie the hypertriglyceridemic phenotype in insulin resistance.
A1 Surendran, R Preethi
A1 Udayyapan, Shanti D
A1 Clemente-Postigo, Mercedes
A1 Havik, Stefan R
A1 Schimmel, Alinda W M
A1 Tinahones, Francisco J
A1 Nieuwdorp, Max
A1 Dallinga-Thie, Geesje M
K1 Mice, Inbred NOD
K1 Microvessels
K1 Receptors, Lipoprotein
K1 Triglycerides
AB GPIHBP1 is a protein localized at the endothelial cell surface that facilitates triglyceride (TG) lipolysis by binding lipoprotein lipase (LPL). Whether Glycosyl Phosphatidyl Inositol high density lipoprotein binding protein 1 (GPIHBP1) function is impaired and may underlie the hyperTG phenotype observed in type 2 diabetes is not yet established. To elucidate the mechanism underlying impaired TG homeostasis in insulin resistance state we studied the effect of insulin on GPIHBP1 protein expression in human microvascular endothelial cells (HMVEC) under flow conditions. Next, we assessed visceral adipose tissue GPIHBP1 protein expression in type 2 diabetes Lepr db/db mouse model as well as in subjects with ranging levels of insulin resistance. We report that insulin reduces the expression of GPIHBP1 protein in HMVECs. Furthermore, GPIHBP1 protein expression in visceral adipose tissue in Lepr db/db mice is significantly reduced as is the active monomeric form of GPIHBP1 as compared to Leprdb/m mice. A similar decrease in GPIHBP1 protein was observed in subjects with increased body weight. GPIHBP1 protein expression was negatively associated with insulin and HOMA-IR. In conclusion, our data suggest that decreased GPIHBP1 availability in insulin resistant state may hamper peripheral lipolysis capacity.
YR 2018
FD 2018-11-08
LK http://hdl.handle.net/10668/13161
UL http://hdl.handle.net/10668/13161
LA en
NO RPS was supported by a grant from the Dutch Heart Association (2010B242). MN is supported by a ZONMW-VIDI grant 2013 [016.146.327] and a Dutch Heart Foundation CVONYoungTalent Grant 2013. MCP was supported by a FPU (Formación de Profesorado Universitario) Grant (AP2009-4537) from the Education Ministry, Madrid (Spain), and by Centros de Investigación Biomédica en Red (CB06/03/0018) of the Instituto de Salud Carlos III (ISCIII) Madrid, Spain.
DS RISalud
RD Apr 10, 2025