N-3 Long-Chain Polyunsaturated Fatty Acid Supplementation Significantly Reduces Liver Oxidative Stress in High Fat Induced Steatosis

Abstract

Omega-3 (n-3) long-chain polyunsaturated fatty acids (n-3 LCPUFA) are associated with several physiological functions, suggesting that their administration may prevent non transmissible chronic diseases. Therefore, we investigate whether dietary n-3 LCPUFA supplementation triggers an antioxidant response preventing liver steatosis in mice fed a high fat diet (HFD) in relation to n-3 LCPUFA levels. Male C57BL/6J mice received (a) control diet (10% fat, 20% protein, 70% carbohydrate), (b) control diet plus n-3 LCPUFA (108 mg/kg/day eicosapentaenoic acid plus 92 mg/kg/day docosahexaenoic acid), (c) HFD (60% fat, 20% protein, 20% carbohydrate), or (d) HFD plus n-3 LCPUFA for 12 weeks. Parameters of liver steatosis, glutathione status, protein carbonylation, and fatty acid analysis were determined, concomitantly with insulin resistance and serum tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, and IL-6 levels. HFD significantly increased total fat and triacylglyceride contents with macrovesicular steatosis, concomitantly with higher fasting serum glucose and insulin levels, HOMA, and serum TNF-α, IL-1β, and IL-6. Reduced and total liver glutathione contents were diminished by HFD, with higher GSSG/GSH ratio and protein carbonylation, n-3 LCPUFA depletion and elevated n-6/n-3 ratio over control values. These changes were either reduced or normalized to control values in animals subjected to HFD and n-3 LCPUFA, with significant increased hepatic total n-3 LCPUFA content and reduced n-6/n-3 ratio being observed after n-3 LCPUFA supplementation alone. So, repletion of liver n-3 LCPUFA levels by n-3 LCPUFA dietary supplementation in HFD obese mice reduces hepatic lipid content, with concomitant antioxidant and anti-inflammatory responses favouring insulin sensitivity.

<em>n-3</em> LCPUFA in the reversal of hepatic steatosis: the role of ACOX and CAT-1

“…This view is supported by the significant correlation between the reduction observed in the hepatic levels of the PPAR-α-regulate enzymes ACOX and CAT-1 (Figure 2A y 2B). From a mechanistic point of view, down-regulation of liver enzymes ACOX and CAT-1 may be ascribed to hepatic n-3 LCPUFA depletion (Araya et al, 2004;Araya et al, 2010;Valenzuela et al, 2012) observed in experimental and human obesity. Different PPAR-α agonist factors are able to lower the number of available triglycerides through different pathways (Araya et al, 2004;Surwit et al, 1988).…”

“…These include a decrease in fatty acids and glycerol mobilization from peripheral tissue lipolisis to the liver (Valenzuela et al, 2012). In addition, n-3 LCPUFA enhances the antioxidant potential of the liver, acting through direct (ROS scavenging) and/or indirect (nuclear transcription factor erythroid 2 related factor 2 (Nrf2) activation) mechanisms, a condition proposed to improve insulin sensitivity (De Leijer et al, 2010;Fernández-Sanchez et al, 2011).…”

“…Previous studies by our group have demonstrated that n-3 LCPUFA supplementation prevents the prosteatotic and pro-inflammatory effects of a high-fat diet (HFD) at the hepatic level (Valenzuela et al, 2012). Furthermore, the dietary change from HFD to a norm caloric diet with n-3 LCPUFA supplementation significantly reduced insulin resistance and liver steatosis when compared to switching HFD to a norm caloric diet alone (Dossi et al, 2014).…”

Effects of Capsaicin Coadministered with Eicosapentaenoic Acid on Obesity-Related Dysregulation in High-Fat-Fed Mice

“…2) Individuals with high-fat diet (HFD)-induced metabolic syndrome have a higher risk of developing non-alcoholic fatty liver disease (NAFLD), 3) which is caused by increased lipogenesis, hyperlipidemia, and increased fat deposition. 4) Dietary fatty acids and those generated by adipose tissue lipolysis contribute to the hepatic fatty acid pool that may be further increased by lipogenesis induced by hyperglycemia and hyperinsulinemia, thus leading to hepatic triglyceride accumulation (steatosis), the hallmark of NAFLD.…”

Ácido docosahexaenoico (DHA), un ácido graso esencial a nivel cerebral

“…humano de los ácidos grasos poliinsaturados, especialmente aquellos de cadena larga (de 20 o más átomos de carbono) (6,7). En este contexto que en las últimas tres décadas el DHA ha adquirido un especial interés por parte de los investigadores debido a sus particulares características físico-químicas y a los efectos bioquímicos y fi siológicos que derivan de su presencia a nivel celular (8).…”