Role of the mixed-lineage protein kinase pathway in the metabolic stress response to obesity
Kant, Shashi ; Barrett, Tamera ; Vertii, Anastassiia ; Noh, Yun Hee ; Jung, Dae Young ; Kim, Jason K ; Davis, Roger J.
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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.
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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