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
Article first published online: 16 JAN 2014
© 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
Molecular Nutrition & Food Research
Volume 58, Issue 6, pages 1333–1341, June 2014
How to Cite
Tapia, G., Valenzuela, R., Espinosa, A., Romanque, P., Dossi, C., Gonzalez-Mañán, D., Videla, L. A. and D'Espessailles, A. (2014), 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. Mol. Nutr. Food Res., 58: 1333–1341. doi: 10.1002/mnfr.201300458
- Issue published online: 5 JUN 2014
- Article first published online: 16 JAN 2014
- Manuscript Accepted: 3 DEC 2013
- Manuscript Revised: 25 NOV 2013
- Manuscript Received: 25 JUN 2013
- FONDECYT (National Fund for Scientific and Technological Development). Grant Number: 1110043
- High-fat diet;
- Liver steatosis;
- n-3 long-chain PUFA;
- Nuclear factor κB;
- Peroxisome proliferator-activated receptor alpha
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).
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.