PERK-dependent regulation of lipogenesis during mouse mammary gland development and adipocyte differentiation
Open Access
- 21 October 2008
- journal article
- research article
- Published by Proceedings of the National Academy of Sciences in Proceedings of the National Academy of Sciences of the United States of America
- Vol. 105 (42), 16314-16319
- https://doi.org/10.1073/pnas.0808517105
Abstract
The role of the endoplasmic reticulum stress-regulated kinase, PERK, in mammary gland function was assessed through generation of a targeted deletion in mammary epithelium. Characterization revealed that PERK is required for functional maturation of milk-secreting mammary epithelial cells. PERK-dependent signaling contributes to lipogenic differentiation in mammary epithelium, and perk deletion inhibits the sustained expression of lipogenic enzymes FAS, ACL, and SCD1. As a result, mammary tissue has reduced lipid content and the milk produced has altered lipid composition, resulting in attenuated pup growth. Consistent with PERK-dependent regulation of the lipogenic pathway, loss of PERK inhibits expression of FAS, ACL, and SCD1 in immortalized murine embryonic fibroblasts when cultured under conditions favoring adipocyte differentiation. These findings implicate PERK as a physiologically relevant regulator of the lipogenic pathway.Keywords
This publication has 46 references indexed in Scilit:
- PERK is essential for neonatal skeletal development to regulate osteoblast proliferation and differentiationJournal of Cellular Physiology, 2008
- Regulation of Hepatic Lipogenesis by the Transcription Factor XBP1Science, 2008
- Dephosphorylation of Translation Initiation Factor 2α Enhances Glucose Tolerance and Attenuates Hepatosteatosis in MiceCell Metabolism, 2008
- Regulation of Sterol Synthesis in EukaryotesAnnual Review of Genetics, 2007
- PERK eIF2 alpha kinase is required to regulate the viability of the exocrine pancreas in miceBMC Cell Biology, 2007
- The GCN2 eIF2α Kinase Regulates Fatty-Acid Homeostasis in the Liver during Deprivation of an Essential Amino AcidCell Metabolism, 2007
- Involvement of Akt in ER-to-Golgi Transport of SCAP/SREBP: A Link between a Key Cell Proliferative Pathway and Membrane SynthesisMolecular Biology of the Cell, 2006
- Cytoprotection by pre-emptive conditional phosphorylation of translation initiation factor 2The EMBO Journal, 2004
- Diabetes Mellitus and Exocrine Pancreatic Dysfunction in Perk−/− Mice Reveals a Role for Translational Control in Secretory Cell SurvivalMolecular Cell, 2001
- A RAPID METHOD OF TOTAL LIPID EXTRACTION AND PURIFICATIONCanadian Journal of Biochemistry and Physiology, 1959