title: Role of the mixed-lineage protein kinase pathway in the metabolic stress response to obesity.
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.
authors: Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA 01605, USA.
authors: Shashi
authors: S
authors: Kant
authors: Tamera
authors: T
authors: Barrett
authors: Anastassiia
authors: A
authors: Vertii
authors: Yun Hee
authors: YH
authors: Noh
authors: Dae Young
authors: DY
authors: Jung
authors: Jason K
authors: JK
authors: Kim
authors: Roger J
authors: RJ
authors: Davis
mesh_terms: D000818:Animals; D059305:Diet, High-Fat / Q000009:adverse effects; D007333:Insulin Resistance; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D020930:MAP Kinase Kinase Kinases / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D009154:Mutation; D009765:Obesity / Q000209:etiology / Q000378:metabolism*; D013312:Stress, Physiological; D000097767:Mitogen-Activated Protein Kinase Kinase Kinase 11
chemical_list: D048031:JNK Mitogen-Activated Protein Kinases; D020930:MAP Kinase Kinase Kinases; D000097767:Mitogen-Activated Protein Kinase Kinase Kinase 11; C490541:Map3k10 protein, mouse
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