Role of the mixed-lineage protein kinase pathway in the metabolic stress response to obesity
Name:
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UMass Chan Affiliations
Department of Medicine, Division of Endocrinology, Metabolism and DiabetesProgram in Molecular Medicine
Document Type
Journal ArticlePublication Date
2013-08-29Keywords
AnimalsDiet, High-Fat
Insulin Resistance
JNK Mitogen-Activated Protein Kinases
MAP Kinase Kinase Kinases
Mice
Mice, Inbred C57BL
Mutation
Obesity
*Stress, PhysiologicalBiochemistryCellular and Molecular Physiology
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Saturated free fatty acid (FFA) is implicated in the metabolic response to obesity. In vitro studies indicate that FFA signaling may be mediated by the mixed-lineage protein kinase (MLK) pathway that activates cJun NH2-terminal kinase (JNK). Here, we examined the role of the MLK pathway in vivo using a mouse model of diet-induced obesity. The ubiquitously expressed MLK2 and MLK3 protein kinases have partially redundant functions. We therefore compared wild-type and compound mutant mice that lack expression of MLK2 and MLK3. MLK deficiency protected mice against high-fat-diet-induced insulin resistance and obesity. Reduced JNK activation and increased energy expenditure contribute to the metabolic effects of MLK deficiency. These data confirm that the MLK pathway plays a critical role in the metabolic response to obesity.Source
Kant S, Barrett T, Vertii A, Noh YH, Jung DY, Kim JK, Davis RJ. Role of the mixed-lineage protein kinase pathway in the metabolic stress response to obesity. Cell Rep. 2013 Aug 29;4(4):681-8. doi: 10.1016/j.celrep.2013.07.019. Link to article on publisher's siteDOI
10.1016/j.celrep.2013.07.019Permanent Link to this Item
http://hdl.handle.net/20.500.14038/44395PubMed ID
23954791Related Resources
Link to Article in PubMedRights
This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial-No Derivative Works License, which permits non-commercial use, distribution, and reproduction in any medium, provided the original author and source are credited.
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