Toll-Like Receptor 4 Knockout Mice Are Protected against Endoplasmic Reticulum Stress Induced by a High-Fat Diet

Autor: Damien Naslain, Patrice D. Cani, Nicolas Pierre, Louise Deldicque, Caroline Barbé, Marc Francaux
Přispěvatelé: UCL - SSS/IONS/CEMO - Pôle Cellulaire et moléculaire, UCL - SSS/IREC/EDIN - Pôle d'endocrinologie, diabète et nutrition, UCL - SSS/LDRI - Louvain Drug Research Institute
Jazyk: angličtina
Rok vydání: 2013
Předmět:
Male
Anatomy and Physiology
Adipose tissue
Biochemistry
Mice
Molecular Cell Biology
Membrane Receptor Signaling
Cellular Stress Responses
Mice
Knockout
Glucose tolerance test
Multidisciplinary
medicine.diagnostic_test
Fatty Acids
Endoplasmic Reticulum Stress
Lipids
medicine.anatomical_structure
Knockout mouse
Medicine
lipids (amino acids
peptides
and proteins)
Cellular Types
Research Article
Signal Transduction
medicine.medical_specialty
XBP1
Science
Biology
Diet
High-Fat
Insulin resistance
Internal medicine
Glucose Intolerance
medicine
Animals
Obesity
Nutrition
Muscle Cells
Endoplasmic reticulum
Skeletal muscle
Glucose Tolerance Test
Lipid Metabolism
medicine.disease
Toll-Like Receptor 4
Metabolism
Endocrinology
Metabolic Disorders
Unfolded protein response
Physiological Processes
Energy Metabolism
Zdroj: PLoS One, Vol. 8, no. 5, p. e65061 (2013)
PLoS ONE, Vol 8, Iss 5, p e65061 (2013)
PLoS ONE
Popis: The purpose of this study was to investigate whether toll-like receptor 4 (TLR4) is implicated in the development of endoplasmic reticulum stress (ER stress) observed after a high-fat diet (HFD) in liver, skeletal muscle and adipose tissue. TLR4(-/-) and C57BL/6J wild-type mice (WT) were fed with chow or HFD (45% calories from fat) during 18 weeks. An oral glucose tolerance-test was performed. The animals were sacrificed in a fasted state and the tissues were removed. TLR4 deletion protected from body weight gain and glucose intolerance induced by HFD whereas energy intake was higher in transgenic mice suggesting larger energy expenditure. HFD induced an ER stress in skeletal muscle, liver and adipose tissue of WT mice as assessed by BiP, CHOP, spliced and unspliced XBP1 and phospho-eIF2α. TLR4(-/-) mice were protected against HFD-induced ER stress. Then, we investigated the main signaling downstream of TLR4 namely the NF-κB pathway, expecting to identify the mechanism by which TLR4 is able to activate ER stress. The mRNA levels of cytokines regulated by NF-κB namely TNFα, IL-1β and IL-6, were not changed after HFD and phospho-IκB-α (ser 32) was not changed. Our results indicate that TLR4 is essential for the development of ER stress related to HFD. Nevertheless, the NFκ-B pathway does not seem to be directly implicated. The reduced fat storage in TLR4(-/-) mice could explain the absence of an ER stress after HFD.
Databáze: OpenAIRE
Externí odkaz: