NDLI: KLF15 Is a Molecular Link between Endoplasmic Reticulum Stress and Insulin Resistance

Content Provider	PubMed Central
Author	Jung, Dae Young Chalasani, Umadevi Pan, Ning Friedline, Randall H. Prosdocimo, Domenick A. Nam, Minwoo Azuma, Yoshihiro Maganti, Rajanikanth Yu, Kristine Velagapudi, Ashish Bryan, O’sullivan-murphy Sartoretto, Juliano L. Jain, Mukesh K. Cooper, Marcus P. Urano, Fumihiko Kim, Jason K. Gray, Susan
Editor	Folli, Franco
Copyright Year	2013
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.
Related Links	http://dx.doi.org/10.1371/journal.pone.0077851
Starting Page	77851
File Format	PDF
ISSN	19326203
e-ISSN	19326203
Journal	PLoS ONE
Issue Number	10
Volume Number	8
Language	English
Publisher	Public Library of Science
Publisher Date	2013-10-01
Access Restriction	Open
Rights Holder	Public Library of Science
Subject Keyword	Biochemistry, Genetics and Molecular Biology(all) Agricultural and Biological Sciences(all) Medicine(all) Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Multidisciplinary

Sl.	Authority	Responsibilities	Communication Details
1	Ministry of Education (GoI), Department of Higher Education	Sanctioning Authority	https://www.education.gov.in/ict-initiatives
2	Indian Institute of Technology Kharagpur	Host Institute of the Project: The host institute of the project is responsible for providing infrastructure support and hosting the project	https://www.iitkgp.ac.in
3	National Digital Library of India Office, Indian Institute of Technology Kharagpur	The administrative and infrastructural headquarters of the project	Dr. B. Sutradhar bsutra@ndl.gov.in
4	Project PI / Joint PI	Principal Investigator and Joint Principal Investigators of the project	Dr. B. Sutradhar bsutra@ndl.gov.in Prof. Saswat Chakrabarti will be added soon
5	Website/Portal (Helpdesk)	Queries regarding NDLI and its services	support@ndl.gov.in
6	Contents and Copyright Issues	Queries related to content curation and copyright issues	content@ndl.gov.in
7	National Digital Library of India Club (NDLI Club)	Queries related to NDLI Club formation, support, user awareness program, seminar/symposium, collaboration, social media, promotion, and outreach	clubsupport@ndl.gov.in
8	Digital Preservation Centre (DPC)	Assistance with digitizing and archiving copyright-free printed books	dpc@ndl.gov.in
9	IDR Setup or Support	Queries related to establishment and support of Institutional Digital Repository (IDR) and IDR workshops	idr@ndl.gov.in

Differing Endoplasmic Reticulum Stress Response to Excess Lipogenesis versus Lipid Oversupply in Relation to Hepatic Steatosis and Insulin Resistance

Midkine, a Potential Link between Obesity and Insulin Resistance

Endoplasmic Reticulum Redox State Is Not Perturbed by Pharmacological or Pathological Endoplasmic Reticulum Stress in Live Pancreatic β-Cells

Endoplasmic Reticulum Stress–Induced Resistance to Doxorubicin Is Reversed by Paeonol Treatment in Human Hepatocellular Carcinoma Cells

Endoplasmic Reticulum Stress Impairs Insulin Receptor Signaling in the Brains of Obese Rats

Protein Tyrosine Phosphatase 1B and Insulin Resistance: Role of Endoplasmic Reticulum Stress/Reactive Oxygen Species/Nuclear Factor Kappa B Axis

Endoplasmic Reticulum Stress Is Increased in Adipose Tissue of Women with Gestational Diabetes

TBL2 Is a Novel PERK-Binding Protein that Modulates Stress-Signaling and Cell Survival during Endoplasmic Reticulum Stress

Regulation of Sumo mRNA during Endoplasmic Reticulum Stress

KLF15 Is a Molecular Link between Endoplasmic Reticulum Stress and Insulin Resistance

Similar Documents

Differing Endoplasmic Reticulum Stress Response to Excess Lipogenesis versus Lipid Oversupply in Relation to Hepatic Steatosis and Insulin Resistance

Midkine, a Potential Link between Obesity and Insulin Resistance

Endoplasmic Reticulum Redox State Is Not Perturbed by Pharmacological or Pathological Endoplasmic Reticulum Stress in Live Pancreatic β-Cells

Endoplasmic Reticulum Stress–Induced Resistance to Doxorubicin Is Reversed by Paeonol Treatment in Human Hepatocellular Carcinoma Cells

Endoplasmic Reticulum Stress Impairs Insulin Receptor Signaling in the Brains of Obese Rats

Protein Tyrosine Phosphatase 1B and Insulin Resistance: Role of Endoplasmic Reticulum Stress/Reactive Oxygen Species/Nuclear Factor Kappa B Axis

Endoplasmic Reticulum Stress Is Increased in Adipose Tissue of Women with Gestational Diabetes

TBL2 Is a Novel PERK-Binding Protein that Modulates Stress-Signaling and Cell Survival during Endoplasmic Reticulum Stress

Regulation of Sumo mRNA during Endoplasmic Reticulum Stress

KLF15 Is a Molecular Link between Endoplasmic Reticulum Stress and Insulin Resistance