Elsevier

Metabolism

Volume 109, August 2020, 154283
Metabolism

Basic Science
Fortifying diet with rapeseed oil instead of butterfat attenuates the progression of diet-induced non-alcoholic fatty liver disease (NAFLD) and impairment of glucose tolerance

https://doi.org/10.1016/j.metabol.2020.154283Get rights and content
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Highlights

  • Exchanging butterfat with rapeseed oil attenuates development of diet-induced NAFLD.

  • Replacing butterfat with rapeseed oil can abolish development of glucose intolerance.

  • Rapeseed oil lowers bacterial endotoxin levels in portal vein.

  • Rapeseed oil attenuates induction of TLR4-dependent signaling cascades in liver.

Abstract

Background

Absolute dietary fat intake but even more so fatty acid pattern is discussed to be critical in the development of non-alcoholic fatty liver disease (NAFLD). Here, we determined if switching a butterfat enriched diet to a rapeseed oil (RO) enriched diet affects progression of an existing NAFLD and glucose intolerance in mice.

Methods

For eight weeks, female C57Bl/6J mice were either fed a liquid control (C) or a butterfat-, fructose- and cholesterol-rich diet (BFC, 25E% butterfat) to induce early signs of steatohepatitis and glucose intolerance in mice. For additional five weeks mice received either BFC or C or a fat-, fructose- and cholesterol-rich and control diet, in which butterfat was replaced with RO (ROFC and CRO). Markers of glucose metabolism, liver damage and intestinal barrier were assessed.

Results

Exchanging butterfat with RO attenuated the progression of BFC diet-induced NAFLD and glucose intolerance. Beneficial effects of RO were associated with lower portal endotoxin levels and an attenuation of the induction of the toll-like receptor-4-dependent signaling cascades in liver. Peroxisome proliferator-activated receptor γ activity was induced in small intestine of ROFC-fed mice.

Conclusion

Taken together, exchanging butterfat with RO attenuated the progression of diet-induced steatohepatitis and glucose intolerance in mice.

Abbreviations

4-HNE
4-hydroxynonenal
Acc
acetyl-CoA carboxylase
ALT
alanine transaminase
ANOVA
analysis of variance
AST
aspartate transaminase
AUC
area under the curve
BFC
butterfat-, fructose- and cholesterol-rich diet
C
control diet
CRO
control diet with rapeseed oil
Cramp
cathelicidin-related antimicrobial peptide
Fas
fatty acid synthase
GTT
glucose-tolerance-test
Il
interleukin
Ir
insulin receptor
Irs
insulin receptor substrate
Muc
mucin
NAFLD
non-alcoholic fatty liver disease
NAS
NAFLD activity score
NASH
non-alcoholic steatohepatitis
NOS
nitric oxide synthase
NS
not significant
PAI-1
plasminogen activator inhibitor-1
PPARγ
peroxisome proliferator-activated receptor γ
PUFA
polyunsaturated fatty acids
ROFC
rapeseed oil-, fructose- and cholesterol-rich diet
RO
rapeseed oil
Scd1
stearoyl-CoA desaturase-1
SFA
saturated fatty acids
SEM
standard error of mean
Srebp1c
sterol regulatory element-binding protein-1c
Tlr4
toll-like receptor-4
TNFα
tumor necrosis factor α

Keywords

Canola oil
Endotoxin
Fatty liver
Glucose tolerance
PUFA

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