RT info:eu-repo/semantics/article
T1 Control of Metabolic Homeostasis by Stress Signaling Is Mediated by the Lipocalin NLaz
A1 Hull-Thompson, Julie
A1 Muffat, Julien
A1 Sánchez Romero, Diego
A1 Walker, David W.
A1 Benzer, Seymour
A1 Ganfornina Álvarez, María Dolores
A1 Jasper, Heinrich
K1 Homeostasis
K1 Lipocainas
AB Metabolic homeostasis in metazoans is regulated by endocrine control of insulin/IGF signaling (IIS) activity. Stress andinflammatory signaling pathways—such as Jun-N-terminal Kinase (JNK) signaling—repress IIS, curtailing anabolic processesto promote stress tolerance and extend lifespan. While this interaction constitutes an adaptive response that allowsmanaging energy resources under stress conditions, excessive JNK activity in adipose tissue of vertebrates has been foundto cause insulin resistance, promoting type II diabetes. Thus, the interaction between JNK and IIS has to be tightly regulatedto ensure proper metabolic adaptation to environmental challenges. Here, we identify a new regulatory mechanism bywhich JNK influences metabolism systemically. We show that JNK signaling is required for metabolic homeostasis in fliesand that this function is mediated by the Drosophila Lipocalin family member Neural Lazarillo (NLaz), a homologue ofvertebrate Apolipoprotein D (ApoD) and Retinol Binding Protein 4 (RBP4). Lipocalins are emerging as central regulators ofperipheral insulin sensitivity and have been implicated in metabolic diseases. NLaz is transcriptionally regulated by JNKsignaling and is required for JNK-mediated stress and starvation tolerance. Loss of NLaz function reduces stress resistanceand lifespan, while its over-expression represses growth, promotes stress tolerance and extends lifespan—phenotypes thatare consistent with reduced IIS activity. Accordingly, we find that NLaz represses IIS activity in larvae and adult flies. Ourresults show that JNK-NLaz signaling antagonizes IIS and is critical for metabolic adaptation of the organism toenvironmental challenges. The JNK pathway and Lipocalins are structurally and functionally conserved, suggesting thatsimilar interactions represent an evolutionarily conserved system for the control of metabolic homeostasis.
PB Public Library of Science
SN 1553-7390
YR 2009
FD 2009
LK http://uvadoc.uva.es/handle/10324/6127
UL http://uvadoc.uva.es/handle/10324/6127
LA eng
NO PLoS Genetics, 2009, vol. 5, n. 4, p. 1-19
NO Producción Científica
DS UVaDOC
RD 27-dic-2024