PERK-dependent regulation of lipogenesis during mouse mammary gland development and adipocyte differentiation

Ekaterina Bobrovnikova-Marjon, Georgia Hatzivassiliou, Christina Grigoriadou, Margarita Romero, Douglas R. Cavener, Craig B. Thompson, J. Alan Diehl

Research output: Contribution to journalArticlepeer-review

149 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)16314-16319
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume105
Issue number42
DOIs
StatePublished - Oct 21 2008

All Science Journal Classification (ASJC) codes

  • General

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