UMMS Affiliation

Program in Molecular Medicine; Department of Medicine, Division of Endocrinology, Metabolism and Diabetes

Publication Date

2013-08-29

Document Type

Article

Subjects

Animals; Diet, High-Fat; Insulin Resistance; JNK Mitogen-Activated Protein Kinases; MAP Kinase Kinase Kinases; Mice; Mice, Inbred C57BL; Mutation; Obesity; *Stress, Physiological

Disciplines

Biochemistry | Cellular and Molecular Physiology

Abstract

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.

Rights and Permissions

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.

DOI of Published Version

10.1016/j.celrep.2013.07.019

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 site

Journal/Book/Conference Title

Cell reports

Related Resources

Link to Article in PubMed

PubMed ID

23954791

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