Intestinal IRE1 Is Required for Increased Triglyceride Metabolism and Longer Lifespan under Dietary Restriction. Academic Article uri icon

abstract

  • Dietary restriction (DR) is one of the most robust lifespan-extending interventions in animals. The beneficial effects of DR involve a metabolic adaptation toward increased triglyceride usage. The regulatory mechanism and the tissue specificity of this metabolic switch remain unclear. Here, we show that theIRE1/XBP1 endoplasmic reticulum (ER) stress signaling module mediates metabolic adaptation upon DR in flies by promoting triglyceride synthesis and accumulation in enterocytes (ECs) of the Drosophila midgut. Consistently, IRE1/XBP1 function in ECs is required for increased longevity upon DR. We further identify sugarbabe, a Gli-like zinc-finger transcription factor, as a key mediator of the IRE1/XBP1-regulated induction of de novo lipogenesis in ECs. Overexpression of sugarbabe rescues metabolic and lifespan phenotypes of IRE1 loss-of-function conditions. Our study highlights the critical role of metabolic adaptation of the intestinal epithelium for DR-induced lifespan extension and explores the IRE1/XBP1 signaling pathway regulating this adaptation and influencing lifespan.

published proceedings

  • Cell Rep

altmetric score

  • 22.108

author list (cited authors)

  • Luis, N. M., Wang, L., Ortega, M., Deng, H., Katewa, S. D., Li, P., ... Kapahi, P.

citation count

  • 47

complete list of authors

  • Luis, Nuno Miguel||Wang, Lifen||Ortega, Mauricio||Deng, Hansong||Katewa, Subhash D||Li, Patrick Wai-Lun||Karpac, Jason||Jasper, Heinrich||Kapahi, Pankaj

publication date

  • January 2016