Leprdb/db Mice with Senescence Marker Protein-30 Knockout (Leprdb/dbSmp30Y/-) Exhibit Increases in Small Dense-LDL and Severe Fatty Liver Despite Being Fed a Standard Diet

Yoshitaka Kondo, Goji Hasegawa, Hiroshi Okada, Takafumi Senmaru, Michiaki Fukui, Naoto Nakamura, Morio Sawada, Jo Kitawaki, Takeshi Okanoue, Yuki Kishimoto, Akiko Amano, Naoki Maruyama, Hiroshi Obayashi, Akihito Ishigami

Research output: Contribution to journalArticlepeer-review

15 Citations (Scopus)

Abstract

Background/Aims:The senescence marker protein-30 (SMP30) is a 34 kDa protein originally identified in rat liver that shows decreased levels with age. Several functional studies using SMP30 knockout (Smp30Y/-) mice established that SMP30 functions as an antioxidant and protects against apoptosis. To address the potential role of SMP30 in nonalcoholic fatty liver disease (NAFLD) pathogenesis, we established Smp30Y/- mice on a Leprdb/db background (Leprdb/dbSmp30Y/- mice).Research Design/Principal Findings:Male Leprdb/dbSmp30Y/- mice were fed a standard diet (340 kcal/100 g, fat 5.6%) for 16 weeks whereupon the lipid/lipoprotein profiles, hepatic expression of genes related to lipid metabolism and endoplasmic reticulum stress markers were analyzed by HPLC, quantitative RT-PCR and western blotting, respectively. Changes in the liver at a histological level were also investigated. The amount of SMP30 mRNA and protein in livers was decreased in Leprdb/dbSmp30Y/+ mice compared with Leprdb/+Smp30Y/+ mice. Compared with Leprdb/dbSmp30Y/+ mice, 24 week old Leprdb/dbSmp30Y/- mice showed: i) increased small dense LDL-cho and decreased HDL-cho levels; ii) fatty liver accompanied by numerous inflammatory cells and increased oxidative stress; iii) decreased mRNA expression of genes involved in fatty acid oxidation (PPARα) and lipoprotein uptake (LDLR and VLDLR) but increased CD36 levels; and iv) increased endoplasmic reticulum stress.Conclusion:Our data strongly suggest that SMP30 is closely associated with NAFLD pathogenesis, and might be a possible therapeutic target for NAFLD.

Original languageEnglish
Article numbere65698
JournalPloS one
Volume8
Issue number6
DOIs
Publication statusPublished - 2013 Jun 3
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

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