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Lipoprotein lipase deficiency in chronic kidney disease is accompanied by down-regulation of endothelial GPIHBP1 expression

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Abstract

Background

Chronic renal failure (CRF) is associated with hypertriglyceridemia and impaired clearance of very low density lipoprotein (VLDL) and chylomicrons which are largely due to lipoprotein lipase (LPL) deficiency/dysfunction. After its release from myocytes and adipocytes, LPL binds to the endothelium in the adjacent capillaries where it catalyzes hydrolysis of triglycerides in VLDL and chylomicrons. The novel endothelium-derived molecule, glycosylphosphatidylinositol-anchored binding protein 1 (GPIHBP1), plays a critical role in LPL metabolism and function by anchoring LPL to the endothelium and binding chylomicrons. GPIHBP1-deficient mice and humans exhibit severe hypertriglyceridemia and diminished heparin-releasable LPL, pointing to the critical role of GPIHBP1 in regulation of LPL activity. Given its central role in regulation of LPL activity and triglyceride metabolism, we explored the effect of chronic kidney disease (CKD) on GPIHBP1 expression.

Methods

Expression of GPIHBP1 and LPL were determined by reverse transcriptase-polymerase chain reaction, Western blot and immunohistochemical analyses in the adipose tissue, skeletal muscle and myocardium of rats 12 weeks after 5/6 nephrectomy (CRF) or sham-operation (control).

Results

Compared to the controls, the CRF group exhibited severe hypertriglyceridemia, significant reduction of the skeletal muscle, myocardium and adipose tissue LPL mRNA and protein abundance. This was accompanied by parallel reductions of GPIHBP1 mRNA abundance and immunostaining in the tested tissues.

Conclusions

LPL deficiency in CKD is associated with and compounded by GPIHBP1 deficiency. Together these abnormalities contribute to impaired clearance of triglyceride-rich lipoproteins, diminished availability of lipid fuel for energy storage in adipocytes and energy production in myocytes and consequent hypertriglyceridemia, cachexia, muscle weakness and atherosclerosis.

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Acknowledgment

This study was in part funded by the NIH Accelerating Excellence in Translational Science (AXIS) grant 5U54 RR026138-02 (10-11-KN-G0811C00-UCI).

Conflict of interest

The authors have no conflict of interest to declare and warrant that the results presented in this paper have not been published previously in whole or part, except in abstract format.

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Authors and Affiliations

  1. Division of Nephrology and Hypertension, University of California, Irvine, Irvine, CA, USA

    Nosratola D. Vaziri, Jun Yuan & Zhenmin Ni

  2. Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA

    Susanne B. Nicholas & Keith C. Norris

  3. Charles R. Drew University of Medicine and Science, Los Angeles, CA, USA

    Susanne B. Nicholas & Keith C. Norris

  4. Division of Nephrology and Hypertension, UCI Medical Center, 101 The City Drive, City Tower, Suit 400, Orange, CA, 92868, USA

    Nosratola D. Vaziri

Authors
  1. Nosratola D. Vaziri
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  2. Jun Yuan
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  3. Zhenmin Ni
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  4. Susanne B. Nicholas
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  5. Keith C. Norris
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Correspondence to Nosratola D. Vaziri.

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Vaziri, N.D., Yuan, J., Ni, Z. et al. Lipoprotein lipase deficiency in chronic kidney disease is accompanied by down-regulation of endothelial GPIHBP1 expression. Clin Exp Nephrol 16, 238–243 (2012). https://doi.org/10.1007/s10157-011-0549-3

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  • DOI: https://doi.org/10.1007/s10157-011-0549-3

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