Editorial
Copyright ©2011 Baishideng Publishing Group Co., Limited. All rights reserved.
World J Diabetes. Nov 15, 2011; 2(11): 176-188
Published online Nov 15, 2011. doi: 10.4239/wjd.v2.i11.176
A defect in the activities of Δ6 and Δ5 desaturases and pro-resolution bioactive lipids in the pathobiology of non-alcoholic fatty liver disease
Undurti N Das
Undurti N Das, UND Life Sciences, 13800 Fairhill Road, 321, Shaker Heights, OH 44120, United States
Undurti N Das, School of Biotechnology, Jawaharlal Nehru Technological University, Kakinada-533 003, India
Undurti N Das, Bio-Science Research Centre, Gayatri Vidya Parishad College of Engineering Visakhapatnam-530 048, India
Author contributions: Das UN solely contributed to this paper.
Supported by Ramalingaswami Fellowship of the Department of Biotechnology, India; a grant from the Defense Research and Development Organisation, New Delhi, India
Correspondence to: Undurti N Das, MD, FAMS, UND Life Sciences, 13800 Fairhill Road, 321, Shaker Heights, OH 44120, United States. undurti@hotmail.com
Telephone: +1-216-2315548 Fax: +1-928-8330316
Received: July 4, 2011
Revised: September 28, 2011
Accepted: October 31, 2011
Published online: November 15, 2011
Abstract

Non-alcoholic fatty liver disease (NAFLD) is a low-grade systemic inflammatory condition, since liver and adipose tissue tumor necrosis factor-α (TNF-α) and TNF receptor 1 transcripts and serum TNF-α levels are increased and IL-6-/- mice are less prone to NAFLD. Fatty liver damage caused by high-fat diets is associated with the generation of pro-inflammatory prostaglandin E2 (PGE2). A decrease in the levels of arachidonic acid (AA), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) and the usefulness of EPA and DHA both in the prevention and management of NAFLD has been reported. AA, EPA and DHA and their anti-inflammatory products lipoxins (LXs), resolvins and protectins suppress IL-6 and TNF-α and PGE2 production. These results suggest that the activities of Δ6 and Δ5 desaturases are reduced in NAFLD and hence, the dietary essential fatty acids, linoleic acid (LA) and α-linolenic acid (ALA) are not metabolized to their long-chain products AA, EPA and DHA, the precursors of anti-inflammatory molecules, LXs, resolvins and protectins that could pre vent NAFLD. This suggests that an imbalance between pro- and anti-inflammatory bioactive lipids contribute to NAFLD. Hence, it is proposed that plasma and tissue levels of AA, EPA, DHA and LXs, resolvins and protectins could be used as predictors and prognostic biomarkers of NAFLD. It is suggested that the synthesis and use of more stable analogues of LXs, resolvins and protectins need to be explored in the prevention and management of NAFLD.

Keywords: Prostaglandins, Lipids, Arachidonic acid, Eicosapentaenoic acid, Non-alcoholic fatty liver disease, Docosahexaenoic acid, Lipoxins, Resolvins, Protectins, Cytokines, Free radicals, Hyperlipidemia