肌肉 c-Jun NH2-末端激酶 1 在肥胖引起的胰岛素抵抗中的作用。
Role of muscle c-Jun NH2-terminal kinase 1 in obesity-induced insulin resistance.
机构信息
Howard Hughes Medical Institute, University of Massachusetts Medical School, 373 Plantation Street, Worcester, MA 01605, USA.
出版信息
Mol Cell Biol. 2010 Jan;30(1):106-15. doi: 10.1128/MCB.01162-09.
Abstract
Obesity caused by feeding of a high-fat diet (HFD) is associated with an increased activation of c-Jun NH(2)-terminal kinase 1 (JNK1). Activated JNK1 is implicated in the mechanism of obesity-induced insulin resistance and the development of metabolic syndrome and type 2 diabetes. Significantly, Jnk1(-)(/)(-) mice are protected against HFD-induced obesity and insulin resistance. Here we show that an ablation of the Jnk1 gene in skeletal muscle does not influence HFD-induced obesity. However, muscle-specific JNK1-deficient (M(KO)) mice exhibit improved insulin sensitivity compared with control wild-type (M(WT)) mice. Thus, insulin-stimulated AKT activation is suppressed in muscle, liver, and adipose tissue of HFD-fed M(WT) mice but is suppressed only in the liver and adipose tissue of M(KO) mice. These data demonstrate that JNK1 in muscle contributes to peripheral insulin resistance in response to diet-induced obesity.
摘要
高脂肪饮食喂养引起的肥胖与 c-Jun NH(2)-末端激酶 1（JNK1）的激活增加有关。激活的 JNK1 参与了肥胖引起的胰岛素抵抗以及代谢综合征和 2 型糖尿病的发病机制。重要的是，Jnk1(-)(/)(-) 小鼠对高脂肪饮食诱导的肥胖和胰岛素抵抗具有保护作用。在这里，我们发现骨骼肌中 Jnk1 基因的缺失并不影响高脂肪饮食诱导的肥胖。然而，与对照野生型（M(WT)）小鼠相比，肌肉特异性 JNK1 缺陷（M(KO)）小鼠表现出改善的胰岛素敏感性。因此，高脂肪饮食喂养的 M(WT)小鼠的肌肉、肝脏和脂肪组织中胰岛素刺激的 AKT 激活受到抑制，但仅在 M(KO)小鼠的肝脏和脂肪组织中受到抑制。这些数据表明肌肉中的 JNK1 有助于对饮食诱导的肥胖产生的外周胰岛素抵抗。
相似文献
1
Role of muscle c-Jun NH2-terminal kinase 1 in obesity-induced insulin resistance.肌肉 c-Jun NH2-末端激酶 1 在肥胖引起的胰岛素抵抗中的作用。
Mol Cell Biol. 2010 Jan;30(1):106-15. doi: 10.1128/MCB.01162-09.
2
Differential effects of JNK1 and JNK2 inhibition on murine steatohepatitis and insulin resistance.JNK1和JNK2抑制对小鼠脂肪性肝炎和胰岛素抵抗的不同影响。
Hepatology. 2009 Jan;49(1):87-96. doi: 10.1002/hep.22578.
3
4
JNK1 ablation in mice confers long-term metabolic protection from diet-induced obesity at the cost of moderate skin oxidative damage.小鼠体内JNK1基因缺失可使其免受饮食诱导的肥胖带来的长期代谢影响，但代价是皮肤受到中度氧化损伤。
FASEB J. 2016 Sep;30(9):3124-32. doi: 10.1096/fj.201600393R. Epub 2016 May 26.
5
A stress signaling pathway in adipose tissue regulates hepatic insulin resistance.脂肪组织中的应激信号通路调节肝脏胰岛素抵抗。
Science. 2008 Dec 5;322(5907):1539-43. doi: 10.1126/science.1160794.
6
Rac1 muscle knockout exacerbates the detrimental effect of high-fat diet on insulin-stimulated muscle glucose uptake independently of Akt.Rac1 肌肉基因敲除可独立于 Akt 加重高脂肪饮食对胰岛素刺激的肌肉葡萄糖摄取的有害影响。
J Physiol. 2018 Jun;596(12):2283-2299. doi: 10.1113/JP275602. Epub 2018 May 10.
7
Chronic blockade of nitric oxide synthesis reduces adiposity and improves insulin resistance in high fat-induced obese mice.长期阻断一氧化氮合成可降低高脂诱导的肥胖小鼠的肥胖程度并改善胰岛素抵抗。
Endocrinology. 2007 Oct;148(10):4548-56. doi: 10.1210/en.2006-1371. Epub 2007 Jun 21.
8
cJun NH2-terminal kinase 1 (JNK1): roles in metabolic regulation of insulin resistance.cJun 氨基末端激酶 1（JNK1）：在胰岛素抵抗的代谢调节中的作用。
Trends Biochem Sci. 2010 Sep;35(9):490-6. doi: 10.1016/j.tibs.2010.04.004. Epub 2010 May 7.
9
Substance P (SP)-neurokinin-1 receptor (NK-1R) alters adipose tissue responses to high-fat diet and insulin action.P 物质（SP）-神经激肽-1 受体（NK-1R）改变脂肪组织对高脂肪饮食和胰岛素作用的反应。
Endocrinology. 2011 Jun;152(6):2197-205. doi: 10.1210/en.2010-1345. Epub 2011 Apr 5.
10
c-Jun NH2-terminal kinase activity in subcutaneous adipose tissue but not nuclear factor-kappaB activity in peripheral blood mononuclear cells is an independent determinant of insulin resistance in healthy individuals.皮下脂肪组织中的c-Jun氨基末端激酶活性而非外周血单核细胞中的核因子-κB活性是健康个体胰岛素抵抗的独立决定因素。
Diabetes. 2009 Jun;58(6):1259-65. doi: 10.2337/db08-1725. Epub 2009 Mar 3.
引用本文的文献
1
p38α MAPK Regulation of Energy Metabolism in Skeletal Muscle Offers a Therapeutic Path for Type 2 Diabetes.p38α丝裂原活化蛋白激酶对骨骼肌能量代谢的调节为2型糖尿病提供了一条治疗途径。
Cells. 2025 Aug 18;14(16):1277. doi: 10.3390/cells14161277.
2
Reactive Oxygen Species as Key Molecules in the Pathogenesis of Alcoholic Fatty Liver Disease and Nonalcoholic Fatty Liver Disease: Future Perspectives.活性氧作为酒精性脂肪性肝病和非酒精性脂肪性肝病发病机制中的关键分子：未来展望
Curr Issues Mol Biol. 2025 Jun 17;47(6):464. doi: 10.3390/cimb47060464.
3
JNK1 in SF1 neurons regulates the central action of thyroid hormones on hepatic lipid metabolism.SF1神经元中的JNK1调节甲状腺激素对肝脏脂质代谢的中枢作用。
Mol Metab. 2025 May 24;98:102170. doi: 10.1016/j.molmet.2025.102170.
4
Cow's Milk Bioactive Molecules in the Regulation of Glucose Homeostasis in Human and Animal Studies.牛奶生物活性分子在人类和动物研究中对葡萄糖稳态的调节作用
Foods. 2024 Sep 6;13(17):2837. doi: 10.3390/foods13172837.
5
Revealing Molecular Mechanisms of the Bioactive Saponins from Edible Root of in Combating Obesity.揭示食用根茎类植物生物活性皂苷对抗肥胖的分子机制。
Plants (Basel). 2024 Apr 17;13(8):1123. doi: 10.3390/plants13081123.
6
Immunometabolism in type 2 diabetes mellitus: tissue-specific interactions.2型糖尿病中的免疫代谢：组织特异性相互作用
Arch Med Sci. 2020 Jan 31;19(4):895-911. doi: 10.5114/aoms.2020.92674. eCollection 2023.
7
Signaling pathways and intervention for therapy of type 2 diabetes mellitus.2型糖尿病治疗的信号通路与干预措施
MedComm (2020). 2023 Jun 7;4(3):e283. doi: 10.1002/mco2.283. eCollection 2023 Jun.
8
Metabolic Impact of MKP-2 Upregulation in Obesity Promotes Insulin Resistance and Fatty Liver Disease.MKP-2 上调对肥胖的代谢影响促进胰岛素抵抗和脂肪肝疾病。
Nutrients. 2022 Jun 15;14(12):2475. doi: 10.3390/nu14122475.
9
JNK1 and JNK3: divergent functions in hippocampal metabolic-cognitive function.JNK1 和 JNK3：在海马体代谢认知功能中的不同作用。
Mol Med. 2022 May 4;28(1):48. doi: 10.1186/s10020-022-00471-y.
10
FGF21/adiponectin ratio predicts deterioration in glycemia: a 4.6-year prospective study in China.FGF21/脂联素比值可预测血糖恶化：中国的一项 4.6 年前瞻性研究。
Cardiovasc Diabetol. 2021 Jul 28;20(1):157. doi: 10.1186/s12933-021-01351-1.
本文引用的文献
1
Prevention of steatosis by hepatic JNK1.通过肝 JNK1 预防脂肪变性。
Cell Metab. 2009 Dec;10(6):491-8. doi: 10.1016/j.cmet.2009.09.007.
2
Lipoprotein lipase: from gene to obesity.脂蛋白脂肪酶：从基因到肥胖
Am J Physiol Endocrinol Metab. 2009 Aug;297(2):E271-88. doi: 10.1152/ajpendo.90920.2008. Epub 2009 Mar 24.
3
A stress signaling pathway in adipose tissue regulates hepatic insulin resistance.脂肪组织中的应激信号通路调节肝脏胰岛素抵抗。
Science. 2008 Dec 5;322(5907):1539-43. doi: 10.1126/science.1160794.
4
Skeletal muscle-specific deletion of lipoprotein lipase enhances insulin signaling in skeletal muscle but causes insulin resistance in liver and other tissues.骨骼肌特异性缺失脂蛋白脂肪酶可增强骨骼肌中的胰岛素信号传导，但会导致肝脏和其他组织出现胰岛素抵抗。
Diabetes. 2009 Jan;58(1):116-24. doi: 10.2337/db07-1839. Epub 2008 Oct 24.
5
Identification of a new JNK inhibitor targeting the JNK-JIP interaction site.一种靶向JNK-JIP相互作用位点的新型JNK抑制剂的鉴定。
Proc Natl Acad Sci U S A. 2008 Oct 28;105(43):16809-13. doi: 10.1073/pnas.0805677105. Epub 2008 Oct 15.
6
c-Jun N-terminal kinase pathways in diabetes.糖尿病中的c-Jun氨基末端激酶通路
Int J Biochem Cell Biol. 2008;40(12):2702-6. doi: 10.1016/j.biocel.2008.06.012. Epub 2008 Jul 17.
7
Muscle-specific IRS-1 Ser->Ala transgenic mice are protected from fat-induced insulin resistance in skeletal muscle.肌肉特异性IRS-1丝氨酸突变为丙氨酸的转基因小鼠可免受脂肪诱导的骨骼肌胰岛素抵抗。
Diabetes. 2008 Oct;57(10):2644-51. doi: 10.2337/db06-0454. Epub 2008 Jul 15.
8
PPARdelta/beta: the lobbyist switching macrophage allegiance in favor of metabolism.过氧化物酶体增殖物激活受体δ/β：促使巨噬细胞转而支持新陈代谢的游说者。
Cell Metab. 2008 Jun;7(6):467-9. doi: 10.1016/j.cmet.2008.05.002.
9
Suppression of p53-dependent senescence by the JNK signal transduction pathway.JNK信号转导通路对p53依赖的衰老的抑制作用。
Proc Natl Acad Sci U S A. 2007 Oct 2;104(40):15759-64. doi: 10.1073/pnas.0707782104. Epub 2007 Sep 24.
10
Disordered lipid metabolism and the pathogenesis of insulin resistance.脂质代谢紊乱与胰岛素抵抗的发病机制。
Physiol Rev. 2007 Apr;87(2):507-20. doi: 10.1152/physrev.00024.2006.
Zotero 插件