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• W2097295599 abstract "Obesity places major demands on the protein folding capacity of the endoplasmic reticulum (ER), resulting in ER stress, a condition that promotes hepatic insulin resistance and steatosis. Here we identify the transcription factor, Kruppel-like factor 15 (KLF15), as an essential mediator of ER stress-induced insulin resistance in the liver. Mice with a targeted deletion of KLF15 exhibit increased hepatic ER stress, inflammation, and JNK activation compared to WT mice; however, KLF15 (-/-) mice are protected against hepatic insulin resistance and fatty liver under high-fat feeding conditions and in response to pharmacological induction of ER stress. The mammalian target of rapamycin complex 1 (mTORC1), a key regulator of cellular energy homeostasis, has been shown to cooperate with ER stress signaling pathways to promote hepatic insulin resistance and lipid accumulation. We find that the uncoupling of ER stress and insulin resistance in KLF15 (-/-) liver is associated with the maintenance of a low energy state characterized by decreased mTORC1 activity, increased AMPK phosphorylation and PGC-1α expression and activation of autophagy, an intracellular degradation process that enhances hepatic insulin sensitivity. Furthermore, in primary hepatocytes, KLF15 deficiency markedly inhibits activation of mTORC1 by amino acids and insulin, suggesting a mechanism by which KLF15 controls mTORC1-mediated insulin resistance. This study establishes KLF15 as an important molecular link between ER stress and insulin action." @default.
• W2097295599 created "2016-06-24" @default.
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• W2097295599 date "2013-10-22" @default.
• W2097295599 modified "2023-10-17" @default.
• W2097295599 title "KLF15 Is a Molecular Link between Endoplasmic Reticulum Stress and Insulin Resistance" @default.
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• W2097295599 doi "https://doi.org/10.1371/journal.pone.0077851" @default.
• W2097295599 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/3805598" @default.
• W2097295599 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/24167585" @default.
• W2097295599 hasPublicationYear "2013" @default.
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