Using Caenorhabditis elegans to Uncover Conserved Functions of Omega-3 and Omega-6 Fatty Acids

Jennifer Watts

doi:10.3390/jcm5020019

Abstract

The nematode Caenorhabditis elegans is a powerful model organism to study functions of polyunsaturated fatty acids. The ability to alter fatty acid composition with genetic manipulation and dietary supplementation permits the dissection of the roles of omega-3 and omega-6 fatty acids in many biological process including reproduction, aging and neurobiology. Studies in C. elegans to date have mostly identified overlapping functions of 20-carbon omega-6 and omega-3 fatty acids in reproduction and in neurons, however, specific roles for either omega-3 or omega-6 fatty acids are beginning to emerge. Recent findings with importance to human health include the identification of a conserved Cox-independent prostaglandin synthesis pathway, critical functions for cytochrome P450 derivatives of polyunsaturated fatty acids, the requirements for omega-6 and omega-3 fatty acids in sensory neurons, and the importance of fatty acid desaturation for long lifespan. Furthermore, the ability of C. elegans to interconvert omega-6 to omega-3 fatty acids using the FAT-1 omega-3 desaturase has been exploited in mammalian studies and biotechnology approaches to generate mammals capable of exogenous generation of omega-3 fatty acids.

Highlights

The adage “you are what you eat” is especially true regarding fat
C. elegans research has been crucial for the elucidation of genetic pathways underlying programmed cell death, longevity, and signal transduction pathways that occur during development as well as during carcinogenesis
Studies in C. elegans regarding non-inflammatory functions of polyunsaturated fatty acids (PUFAs) clearly demonstrate that 20-carbon PUFAs play key roles in reproduction and in the nervous system

Summary

Introduction

The adage “you are what you eat” is especially true regarding fat. Specific types of fat in the human diet have important biological consequences on health and wellness. C. elegans lacks the specific elongase activity to produce 22-carbon PUFAs. Strains containing mutations in genes of the fatty acid desaturation pathway facilitate functional studies of PUFAs, because fatty acid composition can be manipulated both genetically and through the diet [20,21,22]. 4. Functions of Omega-6 and Omega-3 Fatty Acids in C. elegans Reproduction: Sperm Guidance and Germ Cell Maintenance. The fat-1 mutant strain, which cannot convert omega-6 fatty acids to omega-3 fatty acids, was more sensitive to dietary DGLA than wild type [32]. A recent study from the Watts lab showed that the negative effects of DGLA in the C. elegans germ line are likely due to the production of specific epoxide derivatives of DGLA, the synthesis of which depend on the cytochrome P450 (CYP) enzyme. May be producing beneficial epoxides from other PUFAs, such as EPA, that could be required for optimal reproduction

Functions of Omega-6 and Omega-3 Fatty Acids in Longevity

Conclusions and Future Studies