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Journal of Biochemistry Advance Access originally published online on April 19, 2008
Journal of Biochemistry 2008 144(2):149-158; doi:10.1093/jb/mvn055
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© 2008 The Japanese Biochemical Society

Elongation and Desaturation of Fatty Acids are Critical in Growth, Lipid Metabolism and Ontogeny of Caenorhabditis elegans

Makoto Horikawa, Toshihisa Nomura, Teppei Hashimoto and Kazuichi Sakamoto*

Graduate School of Life and Environmental Sciences, University of Tsukuba, Tsukuba, Ibaraki 305-8572, Japan

*To whom correspondence should be addressed. Tel: and Fax: 81-29-853-4875, E-mail: sakamoto{at}biol.tsukuba.ac.jp

Received November 9, 2007; Accepted April 2, 2008


   Abstract

Recently, it was reported that a deficit in the mouse stearoyl-CoA desaturase 1 gene decreases biosynthesis and accumulation of fatty acid and revitalizes the β-oxidation of fatty acid. To examine the physiological role of fatty acid desaturase (FAT) and elongase (ELO)-gene transduction in ontogeny, fatty acid accumulation and individual lifespan, we performed bacteria-mediated RNA interference (RNAi) in the nematode Caenorhabditis elegans. Suppression of the expression of FAT-2 gene mRNA caused a drastic decrease in the amount of body fat and defects in egg-hatching. The amount of body fat was markedly decreased, and body size reduced, by down regulation of FAT-6 and FAT-7, whereas lifespan was drastically reduced. RNAi of the FAT-2 gene caused a remarkable increase of the β-oxidation-related gene expression and the DAF-16 transcriptional activity, whereas, ELO-2 RNAi caused a remarkable decrease in fatty acid biosynthesis-related gene expression. Additionally, RNAi of FAT-6 decreased the mRNA levels of the genes involved in fatty acid synthesis, and FAT-7 RNAi increased the mRNA levels of β-oxidation system genes. These results indicated that the elongation and desaturation of fatty acids are integral to various phenomena such as ontogeny and lifespan and play important roles in fatty acid accumulation and consumption.

Key Words: fatty acid desaturase, fatty acid elongase, lipid metabolism, lifespan, ontogeny, RNA interference

Abbreviations: ACC, Acetyl-CoA Carboxylase; ACS, Acyl-CoA Synthetase; DAF, Dauer Form Defective; DGAT, Diacylglycerol Acyltransferase; ECH, Enoyl-CoA Hydratase; ELO, Fatty Acid Elongase; FAS, Fatty Acid Synthase; FASN, Fatty Acid Synthase; FAT, Fatty Acid Desaturase; GPAT, Glycerol 3-Phosphate Acyl Transferase; HNF, Hepatocyte Nuclear Factor; NGM, Nematode Growth Medium; NHR, Nuclear Hormone Receptor; PGC, PPAR gamma Coactivator; PPAR, Peroxisome Proliferator-Activated Receptor; SCD, Stearoyl-CoA Desaturase; SREBP, Sterol Regulated Element Binding Protein


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