Free fatty acids induce mammary epithelial cell death in ketotic dairy cows via endoplasmic reticulum stress
Peer-Reviewed Publication
Updates every hour. Last Updated: 1-Jun-2026 10:16 ET (1-Jun-2026 14:16 GMT/UTC)
High concentrations of free fatty acid (FFA) in ketotic dairy cows activate endoplasmic reticulum (ER) stress pathways, contributing to mammary epithelial cell apoptosis and reduced milk yield. The study sets the stage for in vivo trials to validate ER stress inhibitors like Tauroursodeoxycholate (TUDCA) as practical solutions for managing ketosis and enhancing dairy cows health.
Kyoto, Japan -- A hallmark of Type 2 diabetes is the progressive loss of beta cell mass: cells in the pancreas that produce and release insulin. The endoplasmic reticulum stress response, a cellular pathway that maintains protein homeostasis, plays a critical role in beta cell function and survival, and the protein ATF6α is one of the key regulators of this stress response. However, the significance of ATF6α signaling in the stress-adaptive regulation of beta cell mass has remained unclear, prompting a team of researchers at Kyoto University to investigate.
"Our previous single-cell RNA-sequencing data suggested transient ATF6α upregulation during adaptive beta-cell proliferation, which sparked our interest in its potential role," says first author Daisuke Otani.
The team generated mice lacking ATF6α, specifically in beta cells. They assessed beta cell mass, proliferation and apoptosis, or cell death, of the mice under chronic stress conditions, including high-fat diet and pregnancy. The team also performed complementary in vitro experiments using chronically stressed beta cell lines, and single-cell RNA sequencing using the high-fat diet model.
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