A branched-chain fatty acid is involved in post-embryonic growth control in parallel to the insulin receptor pathway and its biosynthesis is feedback-regulated in C. elegans.
Growth and development of multicellular organisms are controlled by signaling systems that sense nutrition availability and metabolic status. We report a novel and surprising factor in Caenorhabditis elegans development, the monomethyl branched-chain fatty acid C17ISO, a product of leucine catabolism. We show here that C17ISO is an essential constituent in a novel mechanism that acts in parallel with the food-sensing DAF-2 (insulin receptor)/DAF-16 (FOXO) signaling pathway to promote post-embryonic development, and that the two pathways converge on a common target repressing cell cycle. We show that C17ISO homeostasis is regulated by a SREBP-1c-mediated feedback mechanism that is different from the SREBP-1c-mediated regulation of common fatty acid biosynthesis, as well as by peptide uptake and transport. Our data suggest that C17ISO may act as a chemical/nutritional factor in a mechanism that regulates post-embryonic development in response to the metabolic state of the organism.
Kniazeva
Marina
M
Howard Hughes Medical Institute, Department of Molecular, Cellular, and Developmental Biology, University of Colorado, Boulder, Colorado 80309, USA. marinak@colorado.edu
Euler
Tanya
T
Han
Min
M
D000818:Animals; D017173:Caenorhabditis elegans / Q000254:growth & development* / Q000378:metabolism*; D005227:Fatty Acids / Q000096:biosynthesis / Q000502:physiology*; D025461:Feedback, Physiological; D017930:Genes, Reporter; D049452:Green Fluorescent Proteins / Q000378:metabolism; D006706:Homeostasis; D008954:Models, Biological; D034622:RNA Interference; D011972:Receptor, Insulin / Q000235:genetics / Q000378:metabolism*; D051780:Sterol Regulatory Element Binding Protein 1 / Q000378:metabolism; D019076:Transgenes
D005227:Fatty Acids; D051780:Sterol Regulatory Element Binding Protein 1; D049452:Green Fluorescent Proteins; D011972:Receptor, Insulin