<p>The Role of JNk Signaling Pathway in Obesity-Driven Insulin Resistance</p>

Abstract

Obesity is not only closely related to insulin resistance but is one of the main factors leading to the formation of Type 2 Diabetes (T2D) too. The c-Jun N-terminal kinase (JNK) family is a member of the mitogen-activated protein kinase (MAPK) superfamily. JNK is also one of the most investigated signal transducers in obesity and insulin resistance. JNK-centric JNK signaling pathway can be activated by growth factors, cytokines, stress responses, and other factors. Many researches have identified that the activated phosphorylation JNK negatively regulates insulin signaling pathway in insulin resistance which can be simultaneously regulated by multiple signaling pathways related to the JNK signaling pathway. In this review, we provide an overview of the composition of the JNK signaling pathway, its regulation of insulin signaling pathway, and the relationship between the JNK signaling pathway and other pathways in insulin resistance.

Phytosterols: Nutritional Health Players in the Management of Obesity and Its Related Disorders

“…Interestingly, many researchers have demonstrated that obese subjects show an activated phosphorylation of JNK that negatively regulates the insulin signalling pathway. Indeed, upon activation, JNK is translocated from the cytoplasm into the nucleus, thus promoting the expression of several pro-inflammatory genes and protein synthesis (e.g., IL-1β, TNFα, IL-8, and IL-6), impairing glucose tolerance by obesity-induced insulin resistance [ 72 ]. Similarly, inappropriately increased activation of p38 MAPK has been suggested to contribute to insulin resistance by downregulating the expression of the insulin-responsive glucose transporter (GLUT4) and, in turn, reducing insulin-stimulated glucose uptake [ 73 ].…”

Hyperoxia induces endoplasmic reticulum stress‑associated apoptosis via the IRE1&alpha; pathway in rats with bronchopulmonary dysplasia

“…When ERS was overactivated, in addition to downstream XBP1 inhibition and IRE1α/JNK pathway activation, the induction of apoptosis was observed. Previous studies have demonstrated that JNK-induced apoptosis is an important cause of several diseases, including cancer, liver dysfunction, metabolic disorders and neurodegenerative diseases (38)(39)(40)(41). The apoptosis of lung epithelial cells is an important mechanism of BPD (1).…”

The potential role of sesquiterpene lactones isolated from medicinal plants in the treatment of the metabolic syndrome – A review

“…In the context of obesity, JNK pathways can be activated by proinflammatory cytokines, FFA and reactive oxygen species (ROS), and regulate several nuclear and extra-nuclear substrates, specially the transcription factor activator protein 1 (AP1) which controls the expression of proinflammatory genes and protein synthesis ( e.g. TNF-α, IL-1β, IL-6 and IL-8) ( Pal et al., 2016 ; Feng et al., 2020 ). Deregulated activation of NF-κB and JNK pathways results in increased transcription of IL-6 and TNF-α, which reduce the sensitivity of insulin target cells towards insulin.…”