RRC ID 53371
Author Palikaras K, Mari M, Petanidou B, Pasparaki A, Filippidis G, Tavernarakis N.
Title Ectopic fat deposition contributes to age-associated pathology in Caenorhabditis elegans.
Journal J. Lipid Res.
Abstract Age-dependent collapse of lipid homeostasis results in spillover of lipids and excessive fat deposition in nonadipose tissues. Ectopic fat contributes to lipotoxicity and has been implicated in the development of a metabolic syndrome that increases risk of age-associated diseases. However, the molecular mechanisms coupling ectopic fat accumulation with aging remain obscure. Here, we use nonlinear imaging modalities to visualize and quantify age-dependent ectopic lipid accumulation in Caenorhabditis elegans We find that aging is accompanied by pronounced deposition of lipids in nonadipose tissues, including the nervous system. Importantly, interventions that promote longevity such as low insulin signaling, germ-line loss, and dietary restriction, which effectively delay aging in evolutionary divergent organisms, diminish the rate of ectopic fat accumulation and the size of lipid droplets. Suppression of lipotoxic accumulation of fat in heterologous tissues is dependent on helix-loop-helix (HLH)-30/transcription factor EB (TFEB) and autophagy. Our findings in their totality highlight the pivotal role of HLH-30/TFEB and autophagic processes in the maintenance of lipid homeostasis during aging, in addition to establishing nonlinear imaging as a powerful tool for monitoring ectopic lipid droplet deposition in vivo.
Volume 58(1)
Pages 72-80
Published 2017-1
DOI 10.1194/jlr.M069385
PII jlr.M069385
PMID 27884963
PMC PMC5234711
MeSH Adipose Tissue / metabolism* Adipose Tissue / pathology Aging / genetics Aging / metabolism* Animals Autophagy / genetics Basic Helix-Loop-Helix Leucine Zipper Transcription Factors / genetics* Basic Helix-Loop-Helix Leucine Zipper Transcription Factors / metabolism Caenorhabditis elegans / genetics Caenorhabditis elegans / metabolism Homeostasis Humans Lipid Metabolism / genetics* Longevity / genetics Longevity / physiology Signal Transduction
IF 4.743
C.elegans tm5755 tm4417 tm1954 tm4498 tm1978