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Serglycin protects against high fat diet-induced increase in serum LDL in mice

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Abstract

Proteoglycans have been implicated in regulation of lipoprotein metabolism. However, the impact of serglycin, the major proteoglycan expressed by many hematopoietic- and endothelial cells, on lipoprotein metabolism has not been explored. Here we addressed this issue by comparing several parameters of lipid metabolism in wild type (WT) and serglycin−/− mice, both at baseline and after feeding mice the Paigen diet. We show that, after feeding this diet for 20 weeks, serglycin deficient mice exhibited elevated concentrations of serum LDL in comparison with WT mice, thus suggesting that serglycin protects against an elevation of serum LDL levels after intake of a high-fat diet. Body weight increased in both groups, but only significantly in the serglycin−/− group. To explore the mechanism underlying this phenotype, genome-wide expression analysis was performed on liver tissues from WT and serglycin−/− mice. This analysis showed that serglycin-deficiency is associated with differential expression of numerous genes involved in the regulation of lipid metabolism, suggesting that the impact of serglycin on LDL levels may be related to effects at the gene expression level. In particular, several members of the CYP gene family were differently regulated in serglycin−/− compared with WT mice. Moreover, upstream regulator analysis suggested that several pro-inflammatory pathways, including the NFκB pathway, could contribute to the impact of serglycin on LDL. Hence, the elevation of serum LDL seen in serglycin−/− mice may be linked to dysregulated inflammatory responses. Taken together, our findings introduce serglycin as a novel player in processes that regulate lipid metabolism.

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Acknowledgments

This work was supported by grants from Institute of Basic Medical Sciences, University of Oslo, The Throne Holst Foundation, Freia Medical Research Fund, The Norwegian Diabetes Association, Anders Jahres Fund and The Swedish Research Council.

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Authors and Affiliations

  1. Department of Nutrition, Institute of Basic Medical Sciences, Faculty of Medicine, University of Oslo, Pb. 1046, Blindern, 0317, Oslo, Norway

    Astri J. Meen, Christian A. Drevon & Svein O. Kolset

  2. Department of Anatomy, Physiology, and Biochemistry, Swedish University of Agricultural Sciences, Uppsala, Sweden

    Gunnar Pejler

  3. Department of Medical Biochemistry and Microbiology, Uppsala University, Uppsala, Sweden

    Gunnar Pejler

  4. Department of Transplant Medicine, Section of Nephrology, Oslo University Hospital, Rikshospitalet, Oslo, Norway

    Trond G. Jenssen

  5. Institute of Clinical Medicine, Faculty of Health Science, University of Tromsø, Tromsø, Norway

    Trond G. Jenssen

  6. Department of Medical Biochemistry, Oslo University Hospital and University of Oslo, Oslo, Norway

    Ole Kristoffer Olstad

  7. Department of Biomedical Sciences and Veterinary Public Health, Swedish University of Agricultural Sciences, Uppsala, Sweden

    Magnus Åbrink

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  1. Astri J. Meen
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Meen, A.J., Drevon, C.A., Pejler, G. et al. Serglycin protects against high fat diet-induced increase in serum LDL in mice. Glycoconj J 32, 703–714 (2015). https://doi.org/10.1007/s10719-015-9621-7

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