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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(s) -
Tapia Gladys,
Valenzuela Rodrigo,
Espinosa Alejandra,
Romanque Pamela,
Dossi Camila,
GonzalezMañán Daniel,
Videla Luis A.,
D'Espessailles Amanda
Publication year - 2014
Publication title -
molecular nutrition and food research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.495
H-Index - 131
eISSN - 1613-4133
pISSN - 1613-4125
DOI - 10.1002/mnfr.201300458
Subject(s) - medicine , endocrinology , steatosis , docosahexaenoic acid , peroxisome proliferator activated receptor , chemistry , inflammation , polyunsaturated fatty acid , biology , receptor , fatty acid , biochemistry
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.