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World J Gastroenterol. Nov 7, 2012; 18(41): 5839-5847
Published online Nov 7, 2012. doi: 10.3748/wjg.v18.i41.5839
Omega-3 fatty acids for the treatment of non-alcoholic fatty liver disease
Matteo Nicola Dario Di Minno, Anna Russolillo, Roberta Lupoli, Pasquale Ambrosino, Alessandro Di Minno, Giovanni Tarantino
Matteo Nicola Dario Di Minno, Anna Russolillo, Pasquale Ambrosino, Alessandro Di Minno, Giovanni Tarantino, Department of Clinical and Experimental Medicine, Regional Reference Centre for Coagulation Disorders, “Federico II” University, 80131 Naples, Italy
Roberta Lupoli, Department of Endocrinology and Oncology, “Federico II” University, 80131 Naples, Italy
Author contributions: Di Minno MND and Russolillo A contributed equally to this paper; Di Minno MND performed the manuscript design, searching strategy and manuscript preparation; Russolillo A performed the clinical studies and manuscript preparation; Lupoli R provided the molecular mechanisms; Ambrosino P provided the animal models; Di Minno A performed the bibliographic search; Tarantino G made critical revisions and manuscript preparation.
Correspondence to: Matteo Nicola Dario Di Minno, MD, Department of Clinical and Experimental Medicine, Regional Reference Centre for Coagulation Disorders, “Federico II” University, Via S. Pansini 5, 80131 Naples, Italy.
Telephone: +39-81-7464323 Fax: +39-81-7464323
Received: March 30, 2012
Revised: June 8, 2012
Accepted: June 28, 2012
Published online: November 7, 2012

Non-alcoholic fatty liver disease (NAFLD) has been recognized as a major health burden. It is the most important cause of chronic liver disease and a major independent cardiovascular risk factor. Lacking a definite treatment for NAFLD, a specific diet and an increase in physical activity represent the most commonly used therapeutic approaches. In this review, major literature data about the use of omega-3 polyunsaturated fatty acids (n-3 PUFAs) as a potential treatment of NAFLD have been described. n-3 PUFAs, besides having a beneficial impact on most of the cardio-metabolic risk factors (hypertension, hyperlipidemia, endothelial dysfunction and atherosclerosis) by regulating gene transcription factors [i.e., peroxisome proliferator-activated receptor (PPAR) α, PPARγ, sterol regulatory element-binding protein-1, carbohydrate responsive element-binding protein], impacts both lipid metabolism and on insulin sensitivity. In addition to an enhancement of hepatic beta oxidation and a decrease of the endogenous lipid production, n-3 PUFAs are able to determine a significant reduction of the expression of pro-inflammatory molecules (tumor necrosis factor-α and interleukin-6) and of oxygen reactive species. Further strengthening the results of the in vitro studies, both animal models and human intervention trials, showed a beneficial effect of n-3 PUFAs on the severity of NAFLD as expressed by laboratory parameters and imaging measurements. Despite available results provided encouraging data about the efficacy of n-3 PUFAs as a treatment of NAFLD in humans, well-designed randomized controlled trials of adequate size and duration, with histological endpoints, are needed to assess the long-term safety and efficacy of PUFA, as well as other therapies, for the treatment of NAFLD and non-alcoholic steatohepatitis patients. It is worthwhile to consider that n-3 PUFAs cannot be synthesized by the human body and must be derived from exogenous sources (fish oil, flaxseeds, olive oil) which are typical foods of the Mediterranean diet, known for its beneficial effects in preventing obesity, diabetes and, in turn, cardiovascular events. According to these data, it is important to consider that most of the beneficial effects of n-3 PUFAs can also be obtained by an equilibrate nutrition program.

Keywords: Hepatic steatosis, Non-alcoholic fatty liver disease, Omega-3 polyunsaturated fatty acids, Animal models