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.

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.

• Authors: Gladys Tapia, Rodrigo Valenzuela, Alejandra Espinosa, Pamela Romanque, Camila Dossi, Daniel Gonzalez-Mañán, Luis A Videla, Amanda D'Espessailles
• Journal: Molecular nutrition & food research (Mol Nutr Food Res) Vol. 58 Issue 6 Pg. 1333-41 (Jun 2014) ISSN: 1613-4133 [Electronic] Germany
• PMID: 24436018 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Chemical References

• DNA-Binding Proteins
• Fatty Acids, Omega-3
• Interleukin-1beta
• NF-kappa B
• PPAR alpha
• RNA, Messenger
• Tumor Necrosis Factor-alpha
• Acyl-CoA Oxidase

Topics

• Acyl-CoA Oxidase (genetics, metabolism)
• Animals
• DNA-Binding Proteins (genetics, metabolism)
• Diet, High-Fat (adverse effects)
• Dietary Supplements
• Fatty Acids, Omega-3 (administration & dosage)
• Fatty Liver (etiology, prevention & control)
• Inflammation (etiology, prevention & control)
• Interleukin-1beta (genetics, metabolism)
• Liver (enzymology)
• Male
• Mice
• Mice, Inbred C57BL
• NF-kappa B (genetics, metabolism)
• Organ Size
• PPAR alpha (genetics, metabolism)
• RNA, Messenger (genetics, metabolism)
• Tumor Necrosis Factor-alpha (genetics, metabolism)
• Up-Regulation