N-3 long-chain PUFA supplementation prevents high fat diet induced mouse liver steatosis and inflammation in relation to PPAR-a upregulation and NF-kB 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- ) and nuclear factor B (NF- B) 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 92mg/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- , tumor necrosis factor alpha (TNF- ), and IL-1 mRNA expression, acyl-CoA oxidase 1 (ACOX1), and carnitine-acyl-CoA transferase 1 (CAT-I) protein contents, and NF- B DNA binding activity weremeasured. HFD significantly decreased liver PPAR- , ACOX1, and CAT-I levels with NF- B activation, higher TNF- and IL-1 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- B activation and PPAR- 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- signaling and diminished NF- B activation.