Genetic Regulation of Unsaturated Fatty Acid Composition in C. elegans

Institute of Biological Chemistry, Washington State University, Pullman, Washington, USA.
PLoS Genetics (Impact Factor: 8.17). 08/2006; 2(7):e108. DOI: 10.1371/journal.pgen.0020108
Source: PubMed

The ratio of saturated to unsaturated fatty acids has a profound affect on the fluidity and function of cellular membranes. Animals, plants, and microorganisms regulate the synthesis of unsaturated fatty acids during changing environmental conditions, as well as in response to dietary nutrients. In this paper the authors use a combination of genetic and biochemical approaches to address the regulation of unsaturated fatty acid synthesis in the roundworm Caenorhabditis elegans. They identify a new transcription factor, NHR-80, that activates the expression of genes encoding delta-9 fatty acid desaturases, the enzymes responsible for catalyzing the insertion of double bonds into saturated fatty acid chains. These unsaturated fatty acids are critical components of membranes, as well as fat storage molecules. Experiments presented here demonstrate that the worms require adequate synthesis of unsaturated fatty acids for survival and that they maintain intricate regulation of the three delta-9 desaturase genes in response to different nutrients. Abnormalities in lipid metabolism lead to obesity and diabetes in humans; this study contributes to our understanding of the regulation of this metabolic pathway.

  • [Show abstract] [Hide abstract]
    ABSTRACT: Consumption of Pu-erh has been reported to result in numerous health benefits, but the mechanisms underlying purported weight-loss and lowering of lipid are poorly understood. Here, we used the nematode Caenorhaditis elegans to explore the water extract of Pu-erh tea (PTE) functions to reduce fat storage. We found that PTE down-regulates the expression of the master fat regulator SBP-1, a homologue of sterol regulatory element binding protein (SREBP) and its target stearoyl-CoA desaturase (SCD), a key enzyme in fat biosynthesis, leading to an increased ratio of stearic acid (C18:0) to oleic acid (C18:1n-9), and subsequently decreased fat storage. We also found that both the pharyngeal pumping rate and food uptake of C. elegans decreased with exposure to PTE. Collectively, these results provide an experimental basis for explaining the ability of Pu-erh tea in promoting inhibition of food uptake and the biosynthesis of fat via SBP-1 and SCD, thereby reducing fat storage.
    PLoS ONE 02/2015; 10(2):e0113815. DOI:10.1371/journal.pone.0113815 · 3.53 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Reproduction is an energetically expensive endeavor that has profound influences on many life history traits, including the length of life. Reduced reproduction is associated with increased longevity in many organisms. Similarly, mating has been reported to shorten the lifespan of females in multiple species. Contemporary studies in model organisms have begun to unravel the molecular complexities that govern the relationship between reproduction and longevity. Here, we discuss recent discoveries that examine the genetic mechanisms by which two contrasting reproductive events—germline loss and successful mating—impact the lifespan of Caenorhabditis elegans. We first describe genes necessary for the longevity associated with germline removal in C. elegans, with particular emphasis on microRNAs (miRNAs) that play essential roles in this paradigm. Next, we discuss current efforts toward molecular characterization of procreative interactions between different sexes that affect lifespan. Together, these studies illustrate how the same genetic pathways may be utilized by different sexes to exert behavioral and physiological changes in response to various reproductive events.
    03/2015; 3(1). DOI:10.1007/s40142-014-0060-8
  • [Show abstract] [Hide abstract]
    ABSTRACT: The field of metabolomics continues to catalog new compounds, but their functional analysis remains technically challenging, and roles beyond metabolism are largely unknown. Unbiased genetic/RNAi screens are powerful tools to identify the in vivo functions of protein-encoding genes, but not of nonproteinaceous compounds such as lipids. They can, however, identify the biosynthetic enzymes of these compounds-findings that are usually dismissed, as these typically synthesize multiple products. Here, we provide a method using follow-on biosynthetic pathway screens to identify the endpoint biosynthetic enzyme and thus the compound through which they act. The approach is based on the principle that all subsequently identified downstream biosynthetic enzymes contribute to the synthesis of at least this one end product. We describe how to systematically target lipid biosynthetic pathways; optimize targeting conditions; take advantage of pathway branchpoints; and validate results by genetic assays and biochemical analyses. This approach extends the power of unbiased genetic/RNAi screens to identify in vivo functions of non-nucleic acid-based metabolites beyond their metabolic roles. It will typically require several months to identify a metabolic end product by biosynthetic pathway screens, but this time will vary widely depending, among other factors, on the end product's location in the pathway, which determines the number of screens required for its identification.
    Nature Protocol 05/2015; 10(5):681-700. DOI:10.1038/nprot.2015.031 · 8.36 Impact Factor