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LXR-dependent enhancer activation regulates the temporal organization of the liver's response to refeeding leading to lipogenic gene overshoot.
Korenfeld, Noga; Gorbonos, Tali; Romero Florian, Maria C; Rotaro, Dan; Goldberg, Dana; Radushkevitz-Frishman, Talia; Charni-Natan, Meital; Bar-Shimon, Meirav; Cummins, Carolyn L; Goldstein, Ido.
Afiliación
  • Korenfeld N; Institute of Biochemistry, Food Science and Nutrition, The Robert H. Smith Faculty of Agriculture, Food and Environment, The Hebrew University of Jerusalem, Rehovot, Israel.
  • Gorbonos T; Institute of Biochemistry, Food Science and Nutrition, The Robert H. Smith Faculty of Agriculture, Food and Environment, The Hebrew University of Jerusalem, Rehovot, Israel.
  • Romero Florian MC; Department of Pharmaceutical Sciences, Leslie Dan Faculty of Pharmacy, University of Toronto, Toronto, ON, Canada.
  • Rotaro D; Institute of Biochemistry, Food Science and Nutrition, The Robert H. Smith Faculty of Agriculture, Food and Environment, The Hebrew University of Jerusalem, Rehovot, Israel.
  • Goldberg D; Institute of Biochemistry, Food Science and Nutrition, The Robert H. Smith Faculty of Agriculture, Food and Environment, The Hebrew University of Jerusalem, Rehovot, Israel.
  • Radushkevitz-Frishman T; Institute of Biochemistry, Food Science and Nutrition, The Robert H. Smith Faculty of Agriculture, Food and Environment, The Hebrew University of Jerusalem, Rehovot, Israel.
  • Charni-Natan M; Institute of Biochemistry, Food Science and Nutrition, The Robert H. Smith Faculty of Agriculture, Food and Environment, The Hebrew University of Jerusalem, Rehovot, Israel.
  • Bar-Shimon M; Institute of Biochemistry, Food Science and Nutrition, The Robert H. Smith Faculty of Agriculture, Food and Environment, The Hebrew University of Jerusalem, Rehovot, Israel.
  • Cummins CL; Department of Pharmaceutical Sciences, Leslie Dan Faculty of Pharmacy, University of Toronto, Toronto, ON, Canada.
  • Goldstein I; Institute of Biochemistry, Food Science and Nutrition, The Robert H. Smith Faculty of Agriculture, Food and Environment, The Hebrew University of Jerusalem, Rehovot, Israel.
PLoS Biol ; 22(9): e3002735, 2024 Sep.
Article en En | MEDLINE | ID: mdl-39241209
ABSTRACT
Transitions between the fed and fasted state are common in mammals. The liver orchestrates adaptive responses to feeding/fasting by transcriptionally regulating metabolic pathways of energy usage and storage. Transcriptional and enhancer dynamics following cessation of fasting (refeeding) have not been explored. We examined the transcriptional and chromatin events occurring upon refeeding in mice, including kinetic behavior and molecular drivers. We found that the refeeding response is temporally organized with the early response focused on ramping up protein translation while the later stages of refeeding drive a bifurcated lipid synthesis program. While both the cholesterol biosynthesis and lipogenesis pathways were inhibited during fasting, most cholesterol biosynthesis genes returned to their basal levels upon refeeding while most lipogenesis genes markedly overshoot above pre-fasting levels. Gene knockout, enhancer dynamics, and ChIP-seq analyses revealed that lipogenic gene overshoot is dictated by LXRα. These findings from unbiased analyses unravel the mechanism behind the long-known phenomenon of refeeding fat overshoot.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Ayuno / Elementos de Facilitación Genéticos / Receptores X del Hígado / Hígado Límite: Animals Idioma: En Revista: PLoS Biol Asunto de la revista: BIOLOGIA Año: 2024 Tipo del documento: Article País de afiliación: Israel Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Ayuno / Elementos de Facilitación Genéticos / Receptores X del Hígado / Hígado Límite: Animals Idioma: En Revista: PLoS Biol Asunto de la revista: BIOLOGIA Año: 2024 Tipo del documento: Article País de afiliación: Israel Pais de publicación: Estados Unidos