Brain JNK and metabolic disease.

Diabetologia
Rubén Nogueiras, Guadalupe Sabio

Abstract

Obesity, which has long since reached epidemic proportions worldwide, is associated with long-term stress to a variety of organs and results in diseases including type 2 diabetes. In the brain, overnutrition induces hypothalamic stress associated with the activation of several signalling pathways, together with central insulin and leptin resistance. This central action of nutrient overload appears very rapidly, suggesting that nutrition-induced hypothalamic stress is a major upstream initiator of obesity and associated diseases. The cellular response to nutrient overload includes the activation of the stress-activated c-Jun N-terminal kinases (JNKs) JNK1, JNK2 and JNK3, which are widely expressed in the brain. Here, we review recent findings on the regulation and effects of these kinases, with particular focus on the hypothalamus, a key brain region in the control of energy and glucose homeostasis. JNK1 blocks the hypothalamic-pituitary-thyroid axis, reducing energy expenditure and promoting obesity. Recently, opposing roles have been identified for JNK1 and JNK3 in hypothalamic agouti gene-related protein (AgRP) neurons: while JNK1 activation in AgRP neurons induces feeding and weight gain and impairs insulin and leptin signal...Continue Reading

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Citations

Feb 7, 2021·International Journal of Molecular Sciences·Patricia Seoane-CollazoMiguel López
Dec 5, 2020·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Hanbyeol MoonSang Woo Kim
Feb 16, 2021·Molecular Metabolism·Beatriz CicuéndezGuadalupe Sabio
Aug 28, 2021·International Journal of Molecular Sciences·Hiroki NishikawaKazuhide Higuchi

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