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

Meen, Astri J (författare)
Drevon, Christian A (författare)
Pejler, Gunnar (författare)
Swedish University of Agricultural Sciences,Sveriges lantbruksuniversitet,Uppsala universitet,Institutionen för medicinsk biokemi och mikrobiologi,Institutionen för anatomi, fysiologi och biokemi,Department of Anatomy, Physiology and Biochemistry (AFB),Uppsala University
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Jenssen, Trond G (författare)
Olstad, Ole Kristoffer (författare)
Åbrink, Magnus (författare)
Swedish University of Agricultural Sciences,Sveriges lantbruksuniversitet,Inst för biomedicin och veterinär folkhälsovetenskap,Department of Biomedical Science and Veterinary Public Health
Kolset, Svein O (författare)
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 (creator_code:org_t)
 
2015-09-21
2015
Engelska.
Ingår i: Glycoconjugate Journal. - : Springer Science and Business Media LLC. - 0282-0080 .- 1573-4986. ; 32:9, s. 703-714
  • Tidskriftsartikel (refereegranskat)
Abstract Ämnesord
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  • 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.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinsk bioteknologi -- Medicinsk bioteknologi (hsv//swe)
MEDICAL AND HEALTH SCIENCES  -- Medical Biotechnology -- Medical Biotechnology (hsv//eng)
NATURVETENSKAP  -- Biologi -- Cellbiologi (hsv//swe)
NATURAL SCIENCES  -- Biological Sciences -- Cell Biology (hsv//eng)

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