JNK at the crossroad of obesity, insulin resistance, and cell stress response

Solinas, Giovanni; Becattini, Barbara

doi:10.1016/j.molmet.2016.12.001

Cited by 306 publications

(230 citation statements)

References 124 publications

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“…A). In contrast, TNF‐α, another classical activator of JNK signaling, robustly induces JNK phosphorylation in both Ulk1/2 LDKO and Ctrl hepatocytes (Fig. B).…”

Section: Resultsmentioning

confidence: 94%

Liver‐specific deficiency of unc‐51 like kinase 1 and 2 protects mice from acetaminophen‐induced liver injury

Sun

Song

et al. 2018

Hepatology

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“…A). In contrast, TNF‐α, another classical activator of JNK signaling, robustly induces JNK phosphorylation in both Ulk1/2 LDKO and Ctrl hepatocytes (Fig. B).…”

Section: Resultsmentioning

confidence: 94%

Liver‐specific deficiency of unc‐51 like kinase 1 and 2 protects mice from acetaminophen‐induced liver injury

Sun

Song

et al. 2018

Hepatology

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“…Different subunits of G α proteins can modulate intracellular signaling cascades. An activation of protein kinase C-θ or c-Jun N-terminal kinases and thereby a negative phosphorylation of IRS could be considered as a possible mechanism involved in LPA signaling [31-33]. Furthermore the activation of GSK-3ß and S6K can also impair intracellular insulin signaling via phosphorylation of IRS [34].…”

Section: Discussionmentioning

confidence: 99%

Lysophosphatidic Acid Inhibits Insulin Signaling in Primary Rat Hepatocytes via the LPA3 Receptor Subtype and is Increased in Obesity

Fayyaz

Japtok

Schumacher

et al. 2017

Cell Physiol Biochem

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Background/Aims: Obesity is a main risk factor for the development of hepatic insulin resistance and it is accompanied by adipocyte hypertrophy and an elevated expression of different adipokines such as autotaxin (ATX). ATX converts lysophosphatidylcholine to lysophosphatidic acid (LPA) and acts as the main producer of extracellular LPA. This bioactive lipid regulates a broad range of physiological and pathological responses by activation of LPA receptors (LPA_1-6). Methods: The activation of phosphatidylinositide 3-kinases (PI₃K) signaling (Akt and GSK-3ß) was analyzed via western blotting in primary rat hepatocytes. Incorporation of glucose into glycogen was measured by using radio labeled glucose. Real-time PCR analysis and pharmacological modulation of LPA receptors were performed. Human plasma LPA levels of obese (BMI > 30, n = 18) and normal weight individuals (BMI 18.5-25, n = 14) were analyzed by liquid chromatography tandem-mass spectrometry (LC-MS/MS). Results: Pretreatment of primary hepatocytes with LPA resulted in an inhibition of insulin-mediated Gck expression, PI₃K activation and glycogen synthesis. Pharmacological approaches revealed that the LPA₃-receptor subtype is responsible for the inhibitory effect of LPA on insulin signaling. Moreover, human plasma LPA concentrations (16: 0 LPA) of obese participants (BMI > 30) are significantly elevated in comparison to normal weight individuals (BMI 18.5-25). Conclusion: LPA is able to interrupt insulin signaling in primary rat hepatocytes via the LPA₃ receptor subtype. Moreover, the bioactive lipid LPA (16: 0) is increased in obesity.

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“…The c‐Jun N‐terminal kinase (JNK) pathway is one of three well‐characterized MAPK pathways involved in the regulation of cellular activities . Recent data link JNK signaling to a range of pathological conditions including neurodegenerative diseases, inflammation, and cancer progression . The JNK kinase family consists of three members, JNK1–3 5 , and JNK1 and JNK2 are the more widely expressed JNK isoforms .…”

Section: Introductionmentioning

confidence: 99%

JNK signaling in cancer cell survival

et al. 2019

Medicinal Research Reviews

203

138

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c‐Jun N‐terminal kinase (JNK) is involved in cancer cell apoptosis; however, emerging evidence indicates that this Janus signaling promotes cancer cell survival. JNK acts synergistically with NF‐κB, JAK/STAT, and other signaling molecules to exert a survival function. JNK positively regulates autophagy to counteract apoptosis, and its effect on autophagy is related to the development of chemotherapeutic resistance. The prosurvival effect of JNK may involve an immune evasion mechanism mediated by transforming growth factor‐β, toll‐like receptors, interferon‐γ, and autophagy, as well as compensatory JNK‐dependent cell proliferation. The present review focuses on recent advances in understanding the prosurvival function of JNK and its role in tumor development and chemoresistance, including a comprehensive analysis of the molecular mechanisms underlying JNK‐mediated cancer cell survival. There is a focus on the specific “Yin and Yang” functions of JNK1 and JNK2 in the regulation of cancer cell survival. We highlight recent advances in our knowledge of the roles of JNK in cancer cell survival, which may provide insight into the distinct functions of JNK in cancer and its potential for cancer therapy.

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JNK at the crossroad of obesity, insulin resistance, and cell stress response

Cited by 306 publications

References 124 publications

Liver‐specific deficiency of unc‐51 like kinase 1 and 2 protects mice from acetaminophen‐induced liver injury

Liver‐specific deficiency of unc‐51 like kinase 1 and 2 protects mice from acetaminophen‐induced liver injury

Lysophosphatidic Acid Inhibits Insulin Signaling in Primary Rat Hepatocytes via the LPA3 Receptor Subtype and is Increased in Obesity

JNK signaling in cancer cell survival

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