Lipids

, Volume 48, Issue 11, pp 1115–1134 | Cite as

Increased Lipid Synthesis and Decreased β-Oxidation in the Liver of SHR/NDmcr-cp (cp/cp) Rats, an Animal Model of Metabolic Syndrome

  • Shizuyo Tanaka
  • Tohru Yamazaki
  • Satoshi Asano
  • Atsushi Mitsumoto
  • Daisuke Kobayashi
  • Naomi Kudo
  • Yoichi Kawashima
Original Article

Abstract

SHR/NDmcr-cp (cp/cp) rats (SHR/NDcp) are an animal model of metabolic syndrome. A previous study of ours revealed drastic increases in the mass of palmitic (16:0), oleic (18:1n-9), palmitoleic (16:1n-7), cis-vaccenic (18:1n-7) and 5,8,11-eicosatrienoic acids in the liver of SHR/NDcp. However, detailed information on the class of lipid accumulated and the mechanism responsible for the overproduction of the accumulated lipid in the liver was not obtained. This study aimed to characterize the class of lipid accumulated and to explore the mechanism underlying the lipid accumulation in the liver of SHR/NDcp, in comparison with SHR/NDmcr-cp (+/+) (lean hypertensive littermates of SHR/NDcp) and Wistar Kyoto rats. In the liver of SHR/NDcp, de novo synthesis of fatty acids (16:0, 18:1n-9 and 16:1n-7) and triacylglycerol (TAG) synthesis were up-regulated and fatty acid β-oxidation was down-regulated. These perturbations of lipid metabolism caused fat accumulation in hepatocytes and accumulation of TAG, which were enriched with 16:0, 18:1n-9 and 16:1n-7, in the liver of SHR/NDcp. On the other hand, no changes were found in hepatic contents of diacylglycerol and unesterified fatty acid (FFA); among FFA, there were no differences in the hepatic concentrations of unesterified 16:0 and stearic acid between SHR/NDcp and two other groups of rats. Moreover, little change was brought about in the expression of genes responsive to endoplasmic reticulum stress in the liver of SHR/NDcp. These results may reinforce the pathophysiological role of stearoyl-CoA desaturase 1 and fatty acid elongase 6 in the liver of SHR/NDcp.

Keywords

Hepatic TAG accumulation MUFA De novo lipogenesis β-Oxidation SHR/NDmcr-cp (cp/cp) rat 

Abbreviations

ACC1

Acetyl-CoA carboxylase 1

ACLY

ATP-citrate lyase

ACSL

Long-chain acyl-CoA synthetase

ATGL

Adipose triglyceride lipase

BSA

Bovine serum albumin

CGI-58

Comparative gene identification-58

CHOP

CCAAT/enhancer binding protein homologous protein

ChREBP

Carbohydrate responsive element-binding protein

CPT1a

Carnitine palmitoyltransferase 1a

DGAT

Acyl-CoA:diacylglycerol acyltransferase

EDTA

Ethylenediaminetetraacetic acid

Elovl

Fatty acid elongase

ER

Endoplasmic reticulum

FABP1

Fatty acid binding protein 1

FABPpm

Plasma membrane-associated fatty acid binding protein

Fads

Fatty acid desaturase

FAS

Fatty acid synthase

FAT/CD36

Fatty acid translocase

FATP

Fatty acid transport protein

GPAT

Glycerol-3-phosphate acyltransferase

GRP78

Glucose-regulated protein 78 kDa

H&E

Hematoxylin and eosin

HOMA-IR

Homeostatic model of insulin-resistance index

LPK

L-type pyruvate kinase

LCAD

Long-chain acyl-CoA dehydrogenase

LXRα

Liver X receptor α

MCAD

Medium-chain acyl-CoA dehydrogenase

ME1

Malic enzyme 1

MS

Metabolic syndrome

NAFLD

Nonalcoholic fatty liver disease

ORO

Oil Red O

PCE

Palmitoyl-CoA chain elongation

PCR

Polymerase chain reaction

PEPCK

Phosphoenolpyruvate carboxykinase

PPARα

Peroxisome proliferator-activated receptor α

SCD

Stearoyl-CoA desaturase

SHR

Spontaneously hypertensive rats

SHR/ND+

SHR/NDmcr-cp (+/+) rats

SHR/NDcp

SHR/NDmcr-cp (cp/cp) rats

SHRSP

Stroke-prone spontaneously hypertensive rats

SREBP-1c

Sterol regulatory element binding protein-1c

s-XBP1

Spliced X-box binding protein 1

TLC

Thin-layer chromatography

VLCAD

Very long-chain acyl-CoA dehydrogenase

WKY

Wistar Kyoto rats

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Copyright information

© AOCS 2013

Authors and Affiliations

  • Shizuyo Tanaka
    • 1
  • Tohru Yamazaki
    • 1
  • Satoshi Asano
    • 2
  • Atsushi Mitsumoto
    • 3
  • Daisuke Kobayashi
    • 1
  • Naomi Kudo
    • 1
  • Yoichi Kawashima
    • 1
  1. 1.Faculty of Pharmaceutical SciencesJosai UniversitySakadoJapan
  2. 2.Department of Pharmaceutical SciencesInternational University of Health and WelfareOhtawaraJapan
  3. 3.Faculty of Pharmaceutical SciencesJosai International UniversityToganeJapan

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