&lt;em&gt;n-3&lt;/em&gt; LCPUFA in the reversal of hepatic steatosis: the role of ACOX and CAT-1

C G Dossi,D González-Mañán,A D’Espessailles,G S Tapia

doi:10.3989/gya.0886152

Abstract

The aim of this study was to investigate the roles of the Acyl co-enzyme A oxidase (ACOX), carnitine acyl transferase I (CAT-1) and activating protein 1 (AP-1) in the reversal of hepatic steatosis with dietary change and n-3 long chain polyunsaturated fatty acid ( n-3 LCPUFA) supplementation. Male C57BL/6J mice were given either a control diet (CD) or a high fat diet (HFD) for 12 weeks, and then continued with the CD or CD plus n-3 LCPUFA for eight weeks. After this period, body and adipose visceral tissue weight were analyzed and liver samples were taken to measure ACOX, CAT-1 and c-jun levels. The dietary change from HFD to a norm caloric diet plus n-3 LCPUFA supplementation significantly reduced liver steatosis and adipose tissue: body weight ratio, along with an increase in the hepatic ACOX and CAT-1 levels and normalization of AP-1 expression that could favor the fatty acid beta-oxidation over lipogenesis and regulate inflammation. These results provide new data on the enzymatic metabolism underlying dietary change to a norm caloric diet plus n-3 LCPUFA supplementation.

Highlights

The non-alcoholic fatty liver disease (NAFLD) is considered to be the hepatic expression of the metabolic syndrome, defined as the clustering of risk factors for cardiovascular disease and type II diabetes, which include hyperglycemia, insulin resistance, hypertriglyceridemia and obesity (Bellentani et al, 2009; Malaguarnera et al, 2009)
At 20 days of age, mice were randomly divided into two diet groups: i) the control diet containing 10% fat, 20% protein, and 70% carbohydrate or ii) a high-fat diet (HFD) containing 60% fat, 20% protein, and 20% carbohydrate (D12492, Research Diets, NJ, USA) from days 1 to 84 (12 weeks). 60% of the fat in the high fat diet (HFD) was provided by the addition of lard in significantly higher amounts compared to the control diet
Reduction in adipose tissue weight and corporal weight ratio, liver steatosis and morphological alterations induced by a HFD with change to the control diet with n-3 LCPUFA supplementation

Summary

Introduction

The non-alcoholic fatty liver disease (NAFLD) is considered to be the hepatic expression of the metabolic syndrome, defined as the clustering of risk factors for cardiovascular disease and type II diabetes, which include hyperglycemia, insulin resistance, hypertriglyceridemia and obesity (Bellentani et al, 2009; Malaguarnera et al, 2009). The establishment of liver steatosis leads to the production of free radicals with a lipid peroxidation response, pro-inflammatory cytokine release (Aronis et al, 2005), and n-3 long-chain polyunsaturated fatty acid (n-3 LCPUFA) depletion, with enhancement in the n-6/n-3 LCPUFA ratio favoring a pro-inflammatory state This n-3 LCPUFA depletion induces changes in the DNA binding activity of the peroxisome proliferator-activated receptor Alfa (PPAR-α) (Valenzuela et al, 2011), with a decrease in PPAR-α phosphorylation eliciting low transcription levels of the target genes for carnitine acyl transferase 1 (CAT-1) and acyl coenzyme A oxidase (ACOX), favoring lipogenesis over fatty acid oxidation (Araya et al, 2004; Araya et al, 2010). CAT-1 is an enzyme that regulates the process of beta oxidation in mitochondria, while ACOX is responsible for fatty acid dehydrogenation to promote the beta oxidation process in the peroxisomes (Barlett et al, 2004; Poirier et al, 2006)

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