Role of brain c‐Jun N‐terminal kinase 2 in the control of the insulin receptor and its relationship with cognitive performance in a high‐fat diet pre‐clinical model
Authors: Blanca M López
Rubén D Castro-Torres
Miren Ettcheto
Patricia R Manzine
Àuria Eritja
Carme Auladell
Antoni Camins
Ester Verdaguer
Manuel Vázquez-Carrera
Jordi Olloquequi
Oriol Busquets
Jaume Folch
Journal: Journal of Neurochemistry (2019)
Discipline: NEUROSCIENCE & BEHAVIOR
Keywords: JNK; ER stress; PTP1B; high-fat diet; metabolism
Affiliations: Departament de Farmacologia Toxicologia i Química Terapèutica Facultat de Farmàcia i Ciències de l'Alimentació Universitat de Barcelona Barcelona Spain, Departament de Bioquímica i Biotecnologia Facultat de Medicina i Ciències de la Salut Universitat Rovira i Virgili Reus Spain, Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas (CIBERNED) Instituto de Salud Carlos III Madrid Spain, Institut de Neurociències Universitat de Barcelona Barcelona Spain, Department of Gerontology Federal University of São Carlos (UFSCar) São Carlos SP Brazil, Departament de Biologia Cel·lular Fisiologia i Immunologia Facultat de Biologia Universitat de Barcelona Barcelona Spain, Departamento de Biología Celular y Molecular C.U.C.B.A. Universidad de Guadalajara y División de Neurociencias Guadalajara Jalisco Mexico, Instituto de Ciencias Biomédicas Facultad de Ciencias de la Salud Universidad Autónoma de Chile Talca Chile, Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM) Instituto de Salud Carlos III Barcelona Spain, Institut de Recerca Sant Joan de Déu (IR‐SJD) Barcelona Spain

Abstract:  Insulin resistance has negative consequences on the physiological functioning of the nervous system. The appearance of type 3 diabetes in the brain leads to the development of the sporadic form of Alzheimer's disease. The c-Jun N-terminal kinases (JNK), a subfamily of the Mitogen Activated Protein Kinases, are enzymes composed by three different isoforms with differential modulatory activity against the insulin receptor (IR) and its substrate. This research focused on understanding the regulatory role of JNK2 on the IR, as well as study the effect of a high-fat diet (HFD) in the brain. Our observations determined how JNK2 ablation did not induce compensatory responses in the expression of the other isoforms but led to an increase in JNKs total activity. HFD-fed animals also showed an increased activity profile of the JNKs. These animals also displayed endoplasmic reticulum stress and up-regulation of the protein tyrosine phosphatase 1B (PTP1B) and the suppressor of cytokine signalling 3 protein. Consequently, a reduction in insulin sensitivity was detected and it is correlated with a decrease on the signalling of the IR. Moreover, cognitive impairment was observed in all groups but only wild-type genotype animals fed with HFD showed neuroinflammatory responses. In conclusion, HFD and JNK2 absence cause alterations in normal cognitive activity by altering the signalling of the IR. These affectations are related to the appearance of endoplasmic reticulum stress and an increase in the levels of inhibitory proteins like PTP1B and suppressor of cytokine signalling 3 protein. Cover Image for this issue: doi: 10.1111/jnc.14502. 

Retracted: No

PubPeer comments:
 Supplemental figure 2B appears to have a repeated band suggesting that the image has been spliced together. Could the authors please provide the uncropped original scans? I did not look elsewhere. *** ![file] , 
 Illustrating this concern using false color. Lanes 2 and 5 for the P-GSK38 band appear unexpectedly similar. It is difficult to understand how this type of issue can occur by error. Could the authors please provide the original uncropped scans? *** ![file] ,