A Stress Signaling Pathway in Adipose Tissue Regulates Hepatic Insulin Resistance

By G. Sabio, Madhumita Das, A. Mora, Zhiyou Zhang, J. Jun, H. Ko, T. Barrett, Jason K. Kim, R. Davis. Science, 2008

614 citations recorded by the source corpus.

A high-fat diet causes activation of the regulatory protein c-Jun NH2-terminal kinase 1 (JNK1) and triggers development of insulin resistance. JNK1 is therefore a potential target for therapeutic treatment of metabolic syndrome. We explored the mechanism of JNK1 signaling by engineering mice in which the Jnk1 gene was ablated selectively in adipose tissue. JNK1 deficiency in adipose tissue suppressed high-fat diet–induced insulin resistance in the liver. JNK1-dependent secretion of the inflammatory cytokine interleukin-6 by adipose tissue caused increased expression of liver SOCS3, a protein that induces hepatic insulin resistance. Thus, JNK1 activation in adipose tissue can cause insulin resistance in the liver.

Subfields: Cancer Research, Epidemiology, Oncology

View Paper: https://www.semanticscholar.org/paper/6ca532eaa51bde92208fd67cc1a7d5c8ce5bb737

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Cancer Research

1. Jerrold M. Olefsky
2. Herbert Tilg
3. A. Moschen
4. K. Walsh
5. J. Avruch
6. S. Shoelson
7. J. Kyriakis
8. M. Donath

In Epidemiology

1. Jerrold M. Olefsky
2. Herbert Tilg
3. A. Moschen
4. M. Pinzani
5. O. Osborn
6. K. Walsh
7. Joanne C. McNelis
8. M. Donath

In Oncology

1. Jerrold M. Olefsky
2. J. Avruch
3. A. Chait
4. J. Kyriakis
5. M. Donath
6. Laura J. den Hartigh

Citations in the corpus

• The cellular and signaling networks linking the immune system and metabolism in disease (2012, background): “, and many reports have suggested that IL-6 has proinflammatory effect”
• Integrating Mechanisms for Insulin Resistance: Common Threads and Missing Links (2012, neutral): “Adipose JNK1 knockout mice are protected from hepatic steatosis and specifically hepatic insulin resistance, though they exhibit similar weight gain and adiposity on a high-fat diet (Sabio et al., 2008).”
• Adipocytokines in Obesity and Metabolic Disease (2014, neutral): “In a mouse model with adipose-specific ablation of JNK1, increased secretion of IL6 was proposed to be the primary reason for systemic insulin resistance (Sabio et al. 2008).”
• Type 2 diabetes as an inflammatory disease (2011, background): “In the liver, this activation occurs in both hepatocytes and myeloid cells such as macrophages, and upregulates the production of pro-inflammatory cytokines, including TNF, IL-6 and IL-1”
• Cellular and Molecular Players in Adipose Tissue Inflammation in the Development of Obesity-induced Insulin Resistance (2013, neutral): “Furthermore, the myeloid cell-specific deletion of Jnk1 did not induce any changes in metabolic phenotypes either, whereas adipocyte-specific deletion of Jnk1 improved obesity-induced insulin resistance [125].”
• Interleukin-6 enhances insulin secretion by increasing glucagon-like peptide-1 secretion from L cells and alpha cells (2011, neutral): “(p M p er 3 0 is le ts ) * e Ctrl Ctrl Ctrl ex (9-39) Ctrl ex (9-39) 30 1.”
• Macrophages, immunity, and metabolic disease. (2014, background): “Finally, ablation of JNK (Han et al., 2013; Sabio et al., 2008; Solinas et al., 2007; Vallerie et al., 2008; Zhang et al., 2011) or IKKb (Arkan et al.”
• The multiple-hit pathogenesis of non-alcoholic fatty liver disease (NAFLD). (2016, background): “[37] Sabio G, Das M, Mora A, et al.”