Journal of Lipid Research
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- Endocrine, Csh, CSA, Nephrology, Aacr, Rupress, Proquest, Aaas, Ama, and Highwire from 1959
Elevated hepatic fatty acid elongase-5 activity corrects dietary fat-induced hyperglycemia in obese C57BL/6J mice.
We tested the hypothesis that elevated hepatic Elovl5 expression attenuates hyperglycemia in high fat diet-induced obese mice. Increasing hepatic Elovl5 activity, by a recombinant adenoviral approach, restored blood glucose & insulin, HOMA-IR and glucose tolerance to normal values in obese mice. Ele...
Sphingosine kinase regulates oxidized low density lipoprotein-mediated calcium oscillations and macrophage survival.
We have shown that these [Ca(2+)](i) oscillations mediate oxLDL's ability to inhibit macrophage apoptosis in response to growth factor deprivation. However, the signal transduction pathways by which oxLDL induces [Ca(2+)](i) oscillations have not been elucidated. In this study, we show that these os...
Saturated fatty acids enhance osteoclast survival.
We investigated the effect of saturated fatty acids (SFA) on osteoclastogenesis. The level of free fatty acids and adiposity in bone marrow was significantly elevated in obese mice. SFA increased osteoclast (OC) survival by preventing apoptosis. SFA caused the production of MIP-1alpha and led to act...
Caveolin-1-dependent and -independent membrane domains
We investigated the contribution of the structural protein caveolin-1 (Cav1) to the overall lipid composition and domain abundance in mouse embryonic fibroblasts (MEFs) from wild-type (WT) or Cav1-deficient (Cav1(-/-)) animals. Our findings show that Cav1 expression had no effect on free (membrane-a...
Highly sensitive quantification of key regulatory oxysterols in biological samples by LC-ESI-MS/MS
We describe a highly sensitive and specific method for the quantification of key regulatory oxysterols in biological samples. This method is based upon a stable isotope dilution technique by liquid chromatography-tandem mass spectrometry (LC-MS/MS). After alkaline hydrolysis of human serum (5 mul) o...
LDLs stimulate p38 MAPKs and wound healing through SR-BI independently of Ras and PI3 kinase.
We have previously determined that LDL stimulation of human skin fibroblasts, used as a model system for adventitial fibroblasts, activates p38 mitogen-activated protein kinases (MAPKs), followed by IL-8 production and increased wound-healing capacity of the cells. The proximal events triggering the...
Scavenger receptor class B type I localizes to a late endosomal compartment.
We have investigated the subcellular distribution of SR-BI. We report that red fluorescent protein-tagged mouse SR-BI (RFP-mSR-BI) colocalizes with the late endosomal and lysosomal markers, Rab7, LBPA, and Rab9. In addition, endogenous SR-BI is also found on lysosomes and colocalizes with LAMP-2 in...
Functional analysis of sites within PCSK9 responsible for hypercholesterolemia.
Mutations within proprotein convertase subtilisin/kexin type 9 (PCSK9) are associated with dominant forms of familial hypercholesterolemia. PCSK9 binds the LDL receptor (LDLR), and addition of PCSK9 to cells promotes degradation of LDLR. PCSK9 mutant proteins associated with hypercholesterolemia (S1...
Separation of cellular nonpolar neutral lipids by normal-phase chromatography and analysis by electrospray ionization mass spectrometry.
Neutral lipids are an important class of hydrophobic compounds found in all cells that play critical roles from energy storage to signal transduction. Several distinct structural families make up this class, and within each family there are numbers of individual molecular species. A solvent extracti...
Secreted PCSK9 downregulates low density lipoprotein receptor through receptor-mediated endocytosis.
We show here that recombinant human PCSK9 expressed in HEK293 cells was readily secreted into the medium, with the prosegment associated with the C-terminal domain. Secreted PCSK9 mediated cell surface LDLR degradation in a concentration- and time-dependent manner when added to HEK293 cells. Accordi...