Research Article Enhanced Amelioration of High-Fat Diet-Induced Fatty Liver by Docosahexaenoic Acid and Lysine Supplementations Hsin-Yu Lin, 1 Chih-Chien Chen, 1 Yu-Jen Chen, 1 Yuan-Yu Lin, 1 Harry J. Mersmann, 1 and Shih-Torng Ding 1,2 1 Department of Animal Science and Technology, National Taiwan University, No. 50, Lane 155, Section 3, Keelung Road, Da’an District, Taipei City 106, Taiwan 2 Institute of Biotechnology, National Taiwan University, No. 81, Changxing Street, Da’an District, Taipei City 106, Taiwan Correspondence should be addressed to Shih-Torng Ding; sding@ntu.edu.tw Received 14 November 2013; Revised 15 April 2014; Accepted 29 April 2014; Published 25 May 2014 Academic Editor: Kanato Yamagata Copyright © 2014 Hsin-Yu Lin et al. his 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. Fatty liver disease is the most common pathological condition in the liver. Here, we generated high-fat diet-(HFD-) induced nonalcoholic fatty liver disease (NAFLD) in mice and tested the efects of docosahexaenoic acid (DHA) and lysine during a four- week regular chow (RC)feeding. Our results showed that 1% lysine and the combination of 1% lysine + 1% DHA reduced body weight. Moreover, serum triglyceride levels were reduced by 1% DHA and 1% lysine, whereas serum alanine transaminase activity was reduced by 1% DHA and 1% DHA + 0.5% lysine. Switching to RC reduced hepatic lipid droplet accumulation, which was further reduced by the addition of DHA or lysine. Furthermore, the mRNA expressions of hepatic proinlammatory cytokines were suppressed by DHA and combinations of DHA + lysine, whereas the mRNA for the lipogenic gene, acetyl-CoA carboxylase 1 (ACC1), was suppressed by DHA. In the gonadal adipose tissues, combinations of DHA and lysine inhibited mRNA expression of lipid metabolism-associated genes, including ACC1, fatty acid synthase, lipoprotein lipase, and perilipin. In conclusion, the present study demonstrated that, in conjunction with RC-induced beneits, supplementation with DHA or lysine further ameliorated the high-fat diet-induced NAFLD and provided an alternative strategy to treat, and potentially prevent, NAFLD. 1. Introduction Obesity, in response to excessive nutrients and energy intake, and inadequate energy expenditure, is recognized as a low- grade and chronic inlammatory state, which leads to the metabolic syndrome, including insulin resistance, type II diabetes, atherosclerosis, hypertension, and fatty liver disease (FLD) [1, 2]. hese pathologies are seriously threatening the health of the world populations and knowledge of the underlying mechanisms will provide insights into the future development of preventive and therapeutic strategies. FLD, also known as hepatosteatosis, is a reversible con- dition characterized by massive accumulation of triglyceride in the liver cells, due to energy overload and impaired hep- atic lipid metabolism [3]. Obesity-associated low-grade and chronic inlammatory response arises from free fatty acid- induced production of proinlammatory cytokines, including TNF-, IL-1, and IL-6, by metabolic tissues, such as the liver, muscle, and adipose tissue, and by iniltrated immune cells [4]. his impairs insulin sensitivity and metabolic home- ostasis, leading to increased hepatic gluconeogenesis and lipogenesis, reduced lipolysis, and reduced muscle glucose uptake and adipose lipolysis [5, 6]. When not properly controlled, FLD may progress toward steatohepatitis or liver cell death, ultimately leading to cirrhosis, liver failure, and hepatocellular carcinoma [3]. he increasing insulin sensitivity is the major approach to treat nonalcoholic FLD (NAFLD) in humans by means of weight loss, exercise, and use of various drugs [7, 8]. Addi- tionally, nutrients such as docosahexaenoic acid (DHA), a n-3 polyunsaturated fatty acid, have beneicial efects in reducing obesity and the metabolic syndrome [9] and reducing the occurrence of NAFLD induced by trans-10, cis-12-conjugated linoleic acid [10, 11]. In terms of liver-associated conditions, Hindawi Publishing Corporation BioMed Research International Volume 2014, Article ID 310981, 11 pages http://dx.doi.org/10.1155/2014/310981