Açai (Euterpe oleracea Mart.) Upregulates Paraoxonase 1 Gene Expression and Activity with Concomitant Reduction of Hepatic Steatosis in High-Fat Diet-Fed Rats

Hindawi Publishing Corporation Oxidative Medicine and Cellular Longevity Volume 2016, Article ID 8379105, 13 pages http://dx.doi.org/10.1155/2016/8379105 Research Article Açai (Euterpe oleracea Mart.) Upregulates Paraoxonase 1 Gene Expression and Activity with Concomitant Reduction of Hepatic Steatosis in High-Fat Diet-Fed Rats Renata Rebeca Pereira,1,2 Isabel Cristina Mallosto Emerich de Abreu,3 Joyce Ferreira da Costa Guerra,4 Nara Nunes Lage,1 Juliana Márcia Macedo Lopes,1 Maísa Silva,5 Wanderson Geraldo de Lima,1,2 Marcelo Eustáquio Silva,1,6 and Maria Lucia Pedrosa1,2 1 Research Center in Biological Sciences, Federal University of Ouro Preto, 35400-000 Ouro Preto, MG, Brazil Department of Biological Sciences, Federal University of Ouro Preto, 35400-000 Ouro Preto, MG, Brazil 3 Federal University of São Paulo, 04039-002 São Paulo, SP, Brazil 4 Postgraduate Program in Health and Nutrition, Federal University of Ouro Preto, 35400-000 Ouro Preto, MG, Brazil 5 Department of Basic Health, Federal University of Juiz de Fora, Governador Valadares Campus, 35010-177 Governador Valadares, MG, Brazil 6 Department of Foods, Federal University of Ouro Preto, 35400-000 Ouro Preto, MG, Brazil 2 Correspondence should be addressed to Maria Lucia Pedrosa; Received 25 March 2016; Revised 15 June 2016; Accepted 11 July 2016 Academic Editor: Borna Relja Copyright © 2016 Renata Rebeca Pereira et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Açai (Euterpe oleracea Mart.), a fruit from the Amazon region, has emerged as a promising source of polyphenols. Açai consumption has been increasing owing to ascribed health benefits and antioxidant properties; however, its effects on hepatic injury are limited. In this study, we evaluated the antioxidant effect of filtered açai pulp on the expression of paraoxonase (PON) isoforms and PON1 activity in rats with nonalcoholic fatty liver disease (NAFLD). The rats were fed a standard AIN-93M (control) diet or a high-fat (HF) diet containing 25% soy oil and 1% cholesterol with or without açai pulp (2 g/day) for 6 weeks. Our results show that açai pulp prevented low-density lipoprotein (LDL) oxidation, increased serum and hepatic PON1 activity, and upregulated the expression of PON1 and ApoA-I in the liver. In HF diet-fed rats, treatment with açai pulp attenuated liver damage, reducing fat infiltration and triglyceride (TG) content. In rats receiving açai, increased serum PON1 activity was correlated with a reduction in hepatic steatosis and hepatic injury. These findings suggest the use of açai as a potential therapy for liver injuries, supporting the idea that dietary antioxidants are a promising approach to enhance the defensive systems against oxidative stress. 1. Introduction Nonalcoholic fatty liver disease (NAFLD) affects 10–30% of the general population, representing a spectrum of diseases ranging from simple steatosis to nonalcoholic steatohepatitis (NASH), NAFLD-associated cirrhosis, and end-stage liver disease [1]. NAFLD also increases the risk of hepatocellular carcinoma (HCC). HCC and end-stage liver disease may markedly increase the risk of liver-related mortality [2]. Oxidative stress is thought to be one of the underlying causes of NAFLD [3, 4]. Accumulation of lipids in hepatocytes impairs the oxidative capacity of the mitochondria, increasing the reduced state of the electron transport chain complexes and stimulating the peroxisomal and microsomal pathways of fat oxidation. As a consequence, reactive oxygen species (ROS) are generated that can induce lipid peroxidation, which in turn may be followed by inflammation and fibrogenesis [5]. Paraoxonase (PON) is associated with a variety of diseases involving oxidative stress [6]. The PON gene family 2 contains three members, PON1, PON2, and PON3 [7, 8]. PON1 is a calcium-dependent esterase closely associated with apolipoprotein A-I (ApoA-I) and high-density lipoprotein (HDL) and has been reported to confer antioxidant properties by decreasing the accumulation of lipid peroxidation products [9, 10]. PON1 prevents the production and accumulation of lipoperoxides in low-density lipoprotein particles (LDL) [11, 12] and protects phospholipids from oxidation in HDL. The liver plays a key role in the synthesis of serum PON1, which hydrolyzes a number of substrates, including paraoxon, phenyl acetate, lipid peroxides, and hydroperoxides [13]. PON3 is also predominantly expressed in the liver and secreted into the plasma, where it has an antioxidant effect against LDL oxidation [14]. PON2 is not detectable in serum but is expressed in many tissues, including brain, liver, kidney, and testis [15], and plays a role in decreasing cellular oxidative stress and the inflammatory response. PON1 activity is reduced in many diseases such as atherosclerosis [16], diabetes mellitus [17], chronic kidney disease [18], and hypercholesterolemia [19]. Deficient serum PON1 activity has been associated with an increased risk for Alzheimer’s disease [20]. In addition, an active role of PON1 in the regulation of oxidative stress, fibrosis, and hepatic cell apoptosis in chronic liver diseases has been suggested [21– 23]. PON1 levels significantly decreased in serum of patients with chronic liver diseases such as NAFLD, hepatitis, and cirrhosis [13, 24]. More relevantly, PON1-deficient mice fed a high-fat high-cholesterol diet showed histological alterations in the liver, suggesting that PON1 plays a major role in protection against oxidative stress on diet-induced fatty liver [25]. Dietary polyphenols, including resveratrol and flavonoids, such as quercetin and curcumin, upregulate PON1 [26, 27]. Recent studies have indicated the sterol regulatory element-binding proteins (SREBPs) as targets of polyphenols [28, 29]. SREBPs play a central role in cellular lipogenesis and lipid homeostasis by controlling the synthesis of fatty acids, triacylglycerols, and cholesterol [30] and comprise three main proteins, termed SREBP-1a, SREBP-1c, and SREBP-2, that are encoded by two genes: SREBP1 and SREBP2. While SREBP-1a and SREBP-1c control the fatty acid pathways, SREBP-2 regulates the cholesterol biosynthetic pathway. It was demonstrated that quercetin upregulates PON1 gene transcription and PON1 activity via SREBP-2 that translocates from the endoplasmic reticulum to the nucleus, where it specifically interacts with sterol responsive-like sequence in PON1 promoter [31]. Polyphenols also might activate the aryl hydrocarbon receptor (AhR), a transcription factor sensor for organic chemicals, and stimulate PON1 transcription activation [32, 33]. Açai (Euterpe oleracea Mart.), a fruit native to the Amazon region, has gained international attention as a functional food owing to its high content of polyphenols and potential health benefits. Most o (...truncated)