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Mol Nutr Food Res. 2014 Jun;58(6):1333-41. doi: 10.1002/mnfr.201300458. Epub 2014 Jan 16.

N-3 long-chain PUFA supplementation prevents high fat diet induced mouse liver steatosis and inflammation in relation to PPAR-α upregulation and NF-κB DNA binding abrogation.

Author information

1
Molecular and Clinical Pharmacology Program, Institute of Biomedical Sciences, Faculty of Medicine, University of Chile, Santiago, Chile.

Abstract

SCOPE:

Dietary n-3 long-chain PUFAs (n-3 LCPUFAs) supplementation was studied in an HFD-induced (HFD is high-fat diet) steatosis and inflammation in relation to peroxisome proliferator-activated receptor alpha (PPAR-α) and nuclear factor κB (NF-κB) signaling.

METHODS AND RESULTS:

Male C57BL/6J mice received (i) control diet (10% fat, 20% protein, 70% carbohydrate), (ii) control diet plus n-3 LCPUFAs (daily doses of 108 mg/kg body weight of eicosapentaenoic acid plus 92 mg/kg body weight of docosahexaenoic acid), (iii) HFD (60% fat, 20% protein, 20% carbohydrate), or (iv) HFD plus n-3 LCPUFAs for 12 wk. PPAR-α, tumor necrosis factor alpha (TNF-α), and IL-1β mRNA expression, acyl-CoA oxidase 1 (ACOX1), and carnitine-acyl-CoA transferase 1 (CAT-I) protein contents, and NF-κB DNA binding activity were measured. HFD significantly decreased liver PPAR-α, ACOX1, and CAT-I levels with NF-κB activation, higher TNF-α and IL-1β expression, and steatosis development. These changes were either reduced or normalized to control values in animals subjected to HFD plus n-3 LCPUFAs, with establishment of an inverse association between NF-κB activation and PPAR-α mRNA expression (r = -0.66, p < 0.0001).

CONCLUSION:

Data presented indicate that n-3 LCPUFAs supplementation prevents liver steatosis and inflammation induced by HFD, with underlying mechanisms involving enhanced PPAR-α signaling and diminished NF-κB activation.

KEYWORDS:

High-fat diet; Liver steatosis; Nuclear factor κB; Peroxisome proliferator-activated receptor alpha; n-3 long-chain PUFA

PMID:
24436018
DOI:
10.1002/mnfr.201300458
[Indexed for MEDLINE]

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