title: Autophagy genes are required for normal lipid levels in C. elegans.
abstract: Autophagy is a cellular catabolic process in which various cytosolic components are degraded. For example, autophagy can mediate lipolysis of neutral lipid droplets. In contrast, we here report that autophagy is required to facilitate normal levels of neutral lipids in C. elegans. Specifically, by using multiple methods to detect lipid droplets including CARS microscopy, we observed that mutants in the gene bec- 1 (VPS30/ATG6/BECN1), a key regulator of autophagy, failed to store substantial neutral lipids in their intestines during development. Moreover, loss of bec-1 resulted in a decline in lipid levels in daf-2 [insulin/IGF-1 receptor (IIR) ortholog] mutants and in germline-less glp-1/Notch animals, both previously recognized to accumulate neutral lipids and have increased autophagy levels. Similarly, inhibition of additional autophagy genes, including unc-51/ULK1/ATG1 and lgg-1/ATG8/MAP1LC3A/LC3 during development, led to a reduction in lipid content. Importantly, the decrease in fat accumulation observed in animals with reduced autophagy did not appear to be due to a change in food uptake or defecation. Taken together, these observations suggest a broader role for autophagy in lipid remodeling in C. elegans.
authors: Sanford-Burnham Medical Research Institute; Del E. Webb Neuroscience, Aging and Stem Cell Research Center, Program of Development and Aging, La Jolla, CA USA.
authors: Louis R
authors: LR
authors: Lapierre
authors: Melissa J
authors: MJ
authors: Silvestrini
authors: Lizbeth
authors: L
authors: Nuñez
authors: Kristina
authors: K
authors: Ames
authors: Sara
authors: S
authors: Wong
authors: Thuc T
authors: TT
authors: Le
authors: Malene
authors: M
authors: Hansen
authors: Alicia
authors: A
authors: Meléndez
mesh_terms: D000818:Animals; D001343:Autophagy; D017173:Caenorhabditis elegans / Q000196:embryology / Q000235:genetics* / Q000502:physiology; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000502:physiology*; D018507:Gene Expression Regulation, Developmental; D007422:Intestines / Q000196:embryology / Q000502:physiology; D008055:Lipids / Q000502:physiology*; D009154:Mutation; D010641:Phenotype; D034622:RNA Interference; D011972:Receptor, Insulin / Q000235:genetics; D051880:Receptors, Notch / Q000235:genetics; D033921:Vesicular Transport Proteins / Q000235:genetics / Q000502:physiology*
chemical_list: D029742:Caenorhabditis elegans Proteins; C060620:Glp-1 protein, C elegans; D008055:Lipids; D051880:Receptors, Notch; D033921:Vesicular Transport Proteins; C477268:bec-1 protein, C elegans; C107483:DAF-2 protein, C elegans; D011972:Receptor, Insulin
keywords: C. elegans; CARS microscopy; Oil-Red-O staining; autophagy; fat storage; intestine; lipid metabolism