DsbA-L prevents obesity-induced inflammation and insulin resistance by suppressing the mtDNA release-activated cGAS-cGAMP-STING pathway
Chronic inflammation in adipose tissue plays a key role in obesity-induced insulin resistance. However, the mechanisms underlying obesity-induced inflammation remain elusive. Here we show that obesity promotes mtDNA release into the cytosol, where it triggers inflammatory responses by activating the...
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| Published in | Proceedings of the National Academy of Sciences - PNAS Vol. 114; no. 46; pp. 12196 - 12201 |
|---|---|
| Main Authors | , , , , , , , , , , , , , , , , , |
| Format | Journal Article |
| Language | English |
| Published |
United States
National Academy of Sciences
14.11.2017
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| Subjects | |
| Online Access | Get full text |
| ISSN | 0027-8424 1091-6490 1091-6490 |
| DOI | 10.1073/pnas.1708744114 |
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| Abstract | Chronic inflammation in adipose tissue plays a key role in obesity-induced insulin resistance. However, the mechanisms underlying obesity-induced inflammation remain elusive. Here we show that obesity promotes mtDNA release into the cytosol, where it triggers inflammatory responses by activating the DNA-sensing cGAS-cGAMP-STING pathway. Fat-specific knockout of disulfide-bond A oxidoreductase-like protein (DsbA-L), a chaperone-like protein originally identified in the mitochondrial matrix, impaired mitochondrial function and promoted mtDNA release, leading to activation of the cGAS-cGAMP-STING pathway and inflammatory responses. Conversely, fat-specific overexpression of DsbA-L protected mice against high-fat diet-induced activation of the cGAS-cGAMP-STING pathway and inflammation. Taken together, we identify DsbA-L as a key molecule that maintains mitochondrial integrity. DsbA-L deficiency promotes inflammation and insulin resistance by activating the cGAS-cGAMP-STING pathway. Our study also reveals that, in addition to its well-characterized roles in innate immune surveillance, the cGAS-cGAMP-STING pathway plays an important role in mediating obesity-induced metabolic dysfunction. |
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| AbstractList | Chronic inflammation in adipose tissue plays a key role in obesity-induced insulin resistance. However, the mechanisms underlying obesity-induced inflammation remain elusive. Here we show that obesity promotes mtDNA release into the cytosol, where it triggers inflammatory responses by activating the DNA-sensing cGAS-cGAMP-STING pathway. Fat-specific knockout of disulfide-bond A oxidoreductase-like protein (DsbA-L), a chaperone-like protein originally identified in the mitochondrial matrix, impaired mitochondrial function and promoted mtDNA release, leading to activation of the cGAS-cGAMP-STING pathway and inflammatory responses. Conversely, fat-specific overexpression of DsbA-L protected mice against high-fat diet-induced activation of the cGAS-cGAMP-STING pathway and inflammation. Taken together, we identify DsbA-L as a key molecule that maintains mitochondrial integrity. DsbA-L deficiency promotes inflammation and insulin resistance by activating the cGAS-cGAMP-STING pathway. Our study also reveals that, in addition to its well-characterized roles in innate immune surveillance, the cGAS-cGAMP-STING pathway plays an important role in mediating obesity-induced metabolic dysfunction. Activation of the cGAMP-cGAS-STING pathway has recently been shown to mediate virus- or bacteria-induced activation of the innate immune response. Here we report that this pathway also plays an important role in obesity-induced inflammation and metabolic dysfunction, beyond its well-characterized roles in innate immune surveillance. We have also identified adipose disulfide-bond A oxidoreductase-like protein as a key regulator of mitochondrial integrity and function, which protects mice from obesity-induced inflammation and insulin resistance by suppressing mtDNA release-induced activation of the cGAS-cGAMP-STING pathway. Our study suggests that targeting the cGAS-cGAMP-STING pathway in adipose tissue may be an effective approach to ameliorating obesity-induced chronic inflammation and its associated metabolic diseases. Chronic inflammation in adipose tissue plays a key role in obesity-induced insulin resistance. However, the mechanisms underlying obesity-induced inflammation remain elusive. Here we show that obesity promotes mtDNA release into the cytosol, where it triggers inflammatory responses by activating the DNA-sensing cGAS-cGAMP-STING pathway. Fat-specific knockout of disulfide-bond A oxidoreductase-like protein (DsbA-L), a chaperone-like protein originally identified in the mitochondrial matrix, impaired mitochondrial function and promoted mtDNA release, leading to activation of the cGAS-cGAMP-STING pathway and inflammatory responses. Conversely, fat-specific overexpression of DsbA-L protected mice against high-fat diet-induced activation of the cGAS-cGAMP-STING pathway and inflammation. Taken together, we identify DsbA-L as a key molecule that maintains mitochondrial integrity. DsbA-L deficiency promotes inflammation and insulin resistance by activating the cGAS-cGAMP-STING pathway. Our study also reveals that, in addition to its well-characterized roles in innate immune surveillance, the cGAS-cGAMP-STING pathway plays an important role in mediating obesity-induced metabolic dysfunction. Chronic inflammation in adipose tissue plays a key role in obesity-induced insulin resistance. However, the mechanisms underlying obesity-induced inflammation remain elusive. Here we show that obesity promotes mtDNA release into the cytosol, where it triggers inflammatory responses by activating the DNA-sensing cGAS-cGAMP-STING pathway. Fat-specific knockout of disulfide-bond A oxidoreductase-like protein (DsbA-L), a chaperone-like protein originally identified in the mitochondrial matrix, impaired mitochondrial function and promoted mtDNA release, leading to activation of the cGAS-cGAMP-STING pathway and inflammatory responses. Conversely, fat-specific overexpression of DsbA-L protected mice against high-fat diet-induced activation of the cGAS-cGAMP-STING pathway and inflammation. Taken together, we identify DsbA-L as a key molecule that maintains mitochondrial integrity. DsbA-L deficiency promotes inflammation and insulin resistance by activating the cGAS-cGAMP-STING pathway. Our study also reveals that, in addition to its well-characterized roles in innate immune surveillance, the cGAS-cGAMP-STING pathway plays an important role in mediating obesity-induced metabolic dysfunction.Chronic inflammation in adipose tissue plays a key role in obesity-induced insulin resistance. However, the mechanisms underlying obesity-induced inflammation remain elusive. Here we show that obesity promotes mtDNA release into the cytosol, where it triggers inflammatory responses by activating the DNA-sensing cGAS-cGAMP-STING pathway. Fat-specific knockout of disulfide-bond A oxidoreductase-like protein (DsbA-L), a chaperone-like protein originally identified in the mitochondrial matrix, impaired mitochondrial function and promoted mtDNA release, leading to activation of the cGAS-cGAMP-STING pathway and inflammatory responses. Conversely, fat-specific overexpression of DsbA-L protected mice against high-fat diet-induced activation of the cGAS-cGAMP-STING pathway and inflammation. Taken together, we identify DsbA-L as a key molecule that maintains mitochondrial integrity. DsbA-L deficiency promotes inflammation and insulin resistance by activating the cGAS-cGAMP-STING pathway. Our study also reveals that, in addition to its well-characterized roles in innate immune surveillance, the cGAS-cGAMP-STING pathway plays an important role in mediating obesity-induced metabolic dysfunction. |
| Author | Zhou, Haiyan Xu, Yong Cervantes, Christopher Liu, Juan Dong, Lily Q. Bai, Juli Li, Zhi Chen, Hongzhi Wang, Fang Gao, Xiaoli O’Connor, Jason C. Hu, Derong Yin, Dongqing Zhang, Bilin Liu, Meilian Liu, Feng He, Sijia Cai, Huan |
| Author_xml | – sequence: 1 givenname: Juli surname: Bai fullname: Bai, Juli organization: Department of Pharmacology, University of Texas Health at San Antonio, San Antonio, TX 78229 – sequence: 2 givenname: Christopher surname: Cervantes fullname: Cervantes, Christopher organization: Department of Pharmacology, University of Texas Health at San Antonio, San Antonio, TX 78229 – sequence: 3 givenname: Juan surname: Liu fullname: Liu, Juan organization: Department of Pharmacology, University of Texas Health at San Antonio, San Antonio, TX 78229 – sequence: 4 givenname: Sijia surname: He fullname: He, Sijia organization: Department of Pharmacology, University of Texas Health at San Antonio, San Antonio, TX 78229 – sequence: 5 givenname: Haiyan surname: Zhou fullname: Zhou, Haiyan organization: Department of Metabolism and Endocrinology, Metabolic Syndrome Research Center, Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, China – sequence: 6 givenname: Bilin surname: Zhang fullname: Zhang, Bilin organization: Department of Pharmacology, University of Texas Health at San Antonio, San Antonio, TX 78229 – sequence: 7 givenname: Huan surname: Cai fullname: Cai, Huan organization: Department of Pharmacology, University of Texas Health at San Antonio, San Antonio, TX 78229 – sequence: 8 givenname: Dongqing surname: Yin fullname: Yin, Dongqing organization: Department of Pharmacology, University of Texas Health at San Antonio, San Antonio, TX 78229 – sequence: 9 givenname: Derong surname: Hu fullname: Hu, Derong organization: Department of Pharmacology, University of Texas Health at San Antonio, San Antonio, TX 78229 – sequence: 10 givenname: Zhi surname: Li fullname: Li, Zhi organization: Department of Pharmacology, University of Texas Health at San Antonio, San Antonio, TX 78229 – sequence: 11 givenname: Hongzhi surname: Chen fullname: Chen, Hongzhi organization: Department of Metabolism and Endocrinology, Metabolic Syndrome Research Center, Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, China – sequence: 12 givenname: Xiaoli surname: Gao fullname: Gao, Xiaoli organization: Department of Biochemistry, University of Texas Health at San Antonio, San Antonio, TX 78229 – sequence: 13 givenname: Fang surname: Wang fullname: Wang, Fang organization: Department of Endocrinology, Third Xiangya Hospital, Central South University, Changsha, Hunan, 410013, China – sequence: 14 givenname: Jason C. surname: O’Connor fullname: O’Connor, Jason C. organization: Department of Pharmacology, University of Texas Health at San Antonio, San Antonio, TX 78229 – sequence: 15 givenname: Yong surname: Xu fullname: Xu, Yong organization: Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030 – sequence: 16 givenname: Meilian surname: Liu fullname: Liu, Meilian organization: Department of Metabolism and Endocrinology, Metabolic Syndrome Research Center, Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, China – sequence: 17 givenname: Lily Q. surname: Dong fullname: Dong, Lily Q. organization: Department of Cell Systems & Anatomy, University of Texas Health at San Antonio, San Antonio, TX 78229 – sequence: 18 givenname: Feng surname: Liu fullname: Liu, Feng organization: Department of Pharmacology, University of Texas Health at San Antonio, San Antonio, TX 78229 |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/29087318$$D View this record in MEDLINE/PubMed |
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| Cites_doi | 10.1016/j.cell.2014.11.036 10.1038/nature05292 10.1159/000358901 10.1038/nrcardio.2016.95 10.1093/jmcb/mjw012 10.1002/eji.201141436 10.1016/j.mito.2013.01.003 10.1038/nri3921 10.1074/jbc.M313357200 10.1038/ni.3558 10.1096/fj.201600985R 10.1016/j.cmet.2014.03.018 10.1016/j.immuni.2013.08.004 10.1073/pnas.1516465112 10.1016/j.immuni.2015.02.002 10.1172/JCI57132 10.1002/ijc.30074 10.1038/nature14156 10.1038/nri2975 10.1016/j.cmet.2014.08.011 10.1073/pnas.94.2.514 10.1126/science.1232458 10.1073/pnas.0806341105 10.1016/j.mito.2009.12.148 10.1042/bj3190749 10.2337/db12-0169 10.1016/j.cell.2015.12.057 10.1172/JCI64125 10.1016/j.immuni.2012.01.009 10.1016/j.molcel.2014.03.040 10.1042/bj2780137 10.1146/annurev.biochem.72.121801.161455 10.1016/j.cell.2014.11.037 10.1007/s13238-015-0222-9 10.1038/nm.3082 10.1186/1479-7364-1-6-460 10.1111/j.1530-0277.2002.tb02621.x 10.1126/scitranslmed.aad1811 10.1073/pnas.1215006109 10.2337/db10-0412 10.4049/jimmunol.1500969 10.1093/jmcb/mjw011 10.1074/jbc.M115.645416 10.1007/978-1-59745-521-3_23 10.1021/bi035832z |
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| Copyright | Volumes 1–89 and 106–114, copyright as a collective work only; author(s) retains copyright to individual articles Copyright National Academy of Sciences Nov 14, 2017 2017 |
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| Keywords | cGAS inflammation insulin resistance DsbA-L obesity |
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| Notes | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 content type line 23 Author contributions: J.B. and F.L. designed research; J.B., C.C., J.L., S.H., H.Z., B.Z., H. Cai, D.Y., D.H., Z.L., H. Chen, X.G., F.W., J.C.O., Y.X., and M.L. performed research; J.B., C.C., J.L., H.Z., H. Cai, X.G., J.C.O., and F.L. analyzed data; and J.B., L.Q.D., and F.L. wrote the paper. Edited by Alan Saltiel, University of California, San Diego, La Jolla, CA, and accepted by Editorial Board Member David J. Mangelsdorf October 4, 2017 (received for review May 26, 2017) |
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| References | e_1_3_3_17_2 e_1_3_3_16_2 e_1_3_3_19_2 e_1_3_3_38_2 e_1_3_3_18_2 e_1_3_3_39_2 e_1_3_3_13_2 e_1_3_3_36_2 e_1_3_3_12_2 e_1_3_3_37_2 e_1_3_3_15_2 e_1_3_3_34_2 e_1_3_3_14_2 e_1_3_3_35_2 e_1_3_3_32_2 e_1_3_3_33_2 e_1_3_3_11_2 e_1_3_3_30_2 e_1_3_3_10_2 e_1_3_3_31_2 e_1_3_3_40_2 e_1_3_3_6_2 e_1_3_3_5_2 e_1_3_3_8_2 e_1_3_3_7_2 e_1_3_3_28_2 e_1_3_3_9_2 e_1_3_3_27_2 e_1_3_3_29_2 e_1_3_3_24_2 e_1_3_3_23_2 e_1_3_3_26_2 e_1_3_3_45_2 e_1_3_3_25_2 e_1_3_3_2_2 e_1_3_3_20_2 e_1_3_3_43_2 e_1_3_3_1_2 e_1_3_3_44_2 e_1_3_3_4_2 e_1_3_3_22_2 e_1_3_3_41_2 e_1_3_3_3_2 e_1_3_3_21_2 e_1_3_3_42_2 27648547 - Nat Immunol. 2016 Sep 20;17 (10 ):1142-9 23258413 - Science. 2013 Feb 15;339(6121):786-91 23993650 - Immunity. 2013 Sep 19;39(3):482-95 25786173 - Immunity. 2015 Mar 17;42(3):406-17 25642965 - Nature. 2015 Apr 23;520(7548):553-7 21633179 - J Clin Invest. 2011 Jun;121(6):2111-7 20034597 - Mitochondrion. 2010 Apr;10(3):253-62 26603901 - Nat Rev Immunol. 2015 Dec;15(12):760-70 24862016 - Interdiscip Top Gerontol. 2014;39:86-107 8920976 - Biochem J. 1996 Nov 1;319 ( Pt 3):749-54 23396211 - Nat Med. 2013 Mar;19(3):313-21 15607001 - Hum Genomics. 2004 Nov;1(6):460-4 23333405 - Mitochondrion. 2013 Mar;13(2):106-18 26939583 - Int J Cancer. 2016 Aug 15;139(4):736-41 25525875 - Cell. 2014 Dec 18;159(7):1563-77 15189144 - Annu Rev Biochem. 2004;73:293-320 20699416 - Diabetes. 2010 Nov;59(11):2809-16 25284742 - Cell Metab. 2014 Nov 4;20(5):827-39 23454757 - J Clin Invest. 2013 Mar;123(3):951-7 26993045 - J Mol Cell Biol. 2016 Apr;8(2):120-8 28232481 - FASEB J. 2017 Jun;31(6):2314-2326 12068261 - Alcohol Clin Exp Res. 2002 Jun;26(6):907-15 23132945 - Proc Natl Acad Sci U S A. 2012 Nov 20;109(47):19386-91 17051205 - Nature. 2006 Oct 19;443(7113):787-95 24746805 - Cell Metab. 2014 Jun 3;19(6):967-80 1883325 - Biochem J. 1991 Aug 15;278 ( Pt 1):137-41 14742434 - J Biol Chem. 2004 Apr 16;279(16):16246-53 26223655 - J Immunol. 2015 Sep 1;195(5):1939-43 19513686 - Methods Mol Biol. 2009;554:383-91 25525874 - Cell. 2014 Dec 18;159(7):1549-62 27303815 - Nat Rev Cardiol. 2016 Jun 15;13(7):386-8 19011089 - Proc Natl Acad Sci U S A. 2008 Nov 25;105(47):18302-7 21597473 - Nat Rev Immunol. 2011 Jun;11(6):389-402 26993047 - J Mol Cell Biol. 2016 Apr;8(2):93-100 26919428 - Cell. 2016 Feb 25;164(5):896-910 22342844 - Immunity. 2012 Mar 23;36(3):401-14 14717589 - Biochemistry. 2004 Jan 20;43(2):352-61 9012815 - Proc Natl Acad Sci U S A. 1997 Jan 21;94(2):514-9 24766893 - Mol Cell. 2014 Apr 24;54(2):289-96 26498951 - Protein Cell. 2016 Jan;7(1):11-6 25739441 - J Biol Chem. 2015 Apr 17;290(16):10143-8 22807031 - Diabetes. 2012 Nov;61(11):2776-86 21469137 - Eur J Immunol. 2011 May;41(5):1196-202 26819198 - Sci Transl Med. 2016 Jan 27;8(323):323rv2 26371324 - Proc Natl Acad Sci U S A. 2015 Oct 20;112(42):E5699-705 |
| References_xml | – ident: e_1_3_3_11_2 doi: 10.1016/j.cell.2014.11.036 – ident: e_1_3_3_39_2 doi: 10.1038/nature05292 – ident: e_1_3_3_36_2 doi: 10.1159/000358901 – ident: e_1_3_3_40_2 doi: 10.1038/nrcardio.2016.95 – ident: e_1_3_3_24_2 doi: 10.1093/jmcb/mjw012 – ident: e_1_3_3_7_2 doi: 10.1002/eji.201141436 – ident: e_1_3_3_6_2 doi: 10.1016/j.mito.2013.01.003 – ident: e_1_3_3_14_2 doi: 10.1038/nri3921 – ident: e_1_3_3_31_2 doi: 10.1074/jbc.M313357200 – ident: e_1_3_3_9_2 doi: 10.1038/ni.3558 – ident: e_1_3_3_16_2 doi: 10.1096/fj.201600985R – ident: e_1_3_3_42_2 doi: 10.1016/j.cmet.2014.03.018 – ident: e_1_3_3_13_2 doi: 10.1016/j.immuni.2013.08.004 – ident: e_1_3_3_27_2 doi: 10.1073/pnas.1516465112 – ident: e_1_3_3_37_2 doi: 10.1016/j.immuni.2015.02.002 – ident: e_1_3_3_2_2 doi: 10.1172/JCI57132 – ident: e_1_3_3_5_2 doi: 10.1002/ijc.30074 – ident: e_1_3_3_4_2 doi: 10.1038/nature14156 – ident: e_1_3_3_41_2 doi: 10.1038/nri2975 – ident: e_1_3_3_44_2 doi: 10.1016/j.cmet.2014.08.011 – ident: e_1_3_3_12_2 doi: 10.1073/pnas.94.2.514 – ident: e_1_3_3_45_2 doi: 10.1126/science.1232458 – ident: e_1_3_3_23_2 doi: 10.1073/pnas.0806341105 – ident: e_1_3_3_43_2 doi: 10.1016/j.mito.2009.12.148 – ident: e_1_3_3_29_2 doi: 10.1042/bj3190749 – ident: e_1_3_3_21_2 doi: 10.2337/db12-0169 – ident: e_1_3_3_22_2 doi: 10.1016/j.cell.2015.12.057 – ident: e_1_3_3_38_2 doi: 10.1172/JCI64125 – ident: e_1_3_3_3_2 doi: 10.1016/j.immuni.2012.01.009 – ident: e_1_3_3_8_2 doi: 10.1016/j.molcel.2014.03.040 – ident: e_1_3_3_15_2 doi: 10.1042/bj2780137 – ident: e_1_3_3_20_2 doi: 10.1146/annurev.biochem.72.121801.161455 – ident: e_1_3_3_10_2 doi: 10.1016/j.cell.2014.11.037 – ident: e_1_3_3_30_2 doi: 10.1007/s13238-015-0222-9 – ident: e_1_3_3_18_2 doi: 10.1038/nm.3082 – ident: e_1_3_3_32_2 doi: 10.1186/1479-7364-1-6-460 – ident: e_1_3_3_35_2 doi: 10.1111/j.1530-0277.2002.tb02621.x – ident: e_1_3_3_1_2 doi: 10.1126/scitranslmed.aad1811 – ident: e_1_3_3_26_2 doi: 10.1073/pnas.1215006109 – ident: e_1_3_3_34_2 doi: 10.2337/db10-0412 – ident: e_1_3_3_28_2 doi: 10.4049/jimmunol.1500969 – ident: e_1_3_3_25_2 doi: 10.1093/jmcb/mjw011 – ident: e_1_3_3_17_2 doi: 10.1074/jbc.M115.645416 – ident: e_1_3_3_19_2 doi: 10.1007/978-1-59745-521-3_23 – ident: e_1_3_3_33_2 doi: 10.1021/bi035832z – reference: 24766893 - Mol Cell. 2014 Apr 24;54(2):289-96 – reference: 21469137 - Eur J Immunol. 2011 May;41(5):1196-202 – reference: 26919428 - Cell. 2016 Feb 25;164(5):896-910 – reference: 19011089 - Proc Natl Acad Sci U S A. 2008 Nov 25;105(47):18302-7 – reference: 25525875 - Cell. 2014 Dec 18;159(7):1563-77 – reference: 14742434 - J Biol Chem. 2004 Apr 16;279(16):16246-53 – reference: 25284742 - Cell Metab. 2014 Nov 4;20(5):827-39 – reference: 9012815 - Proc Natl Acad Sci U S A. 1997 Jan 21;94(2):514-9 – reference: 26939583 - Int J Cancer. 2016 Aug 15;139(4):736-41 – reference: 21597473 - Nat Rev Immunol. 2011 Jun;11(6):389-402 – reference: 12068261 - Alcohol Clin Exp Res. 2002 Jun;26(6):907-15 – reference: 23993650 - Immunity. 2013 Sep 19;39(3):482-95 – reference: 24862016 - Interdiscip Top Gerontol. 2014;39:86-107 – reference: 23132945 - Proc Natl Acad Sci U S A. 2012 Nov 20;109(47):19386-91 – reference: 26603901 - Nat Rev Immunol. 2015 Dec;15(12):760-70 – reference: 25642965 - Nature. 2015 Apr 23;520(7548):553-7 – reference: 19513686 - Methods Mol Biol. 2009;554:383-91 – reference: 28232481 - FASEB J. 2017 Jun;31(6):2314-2326 – reference: 27648547 - Nat Immunol. 2016 Sep 20;17 (10 ):1142-9 – reference: 23396211 - Nat Med. 2013 Mar;19(3):313-21 – reference: 26819198 - Sci Transl Med. 2016 Jan 27;8(323):323rv2 – reference: 22807031 - Diabetes. 2012 Nov;61(11):2776-86 – reference: 17051205 - Nature. 2006 Oct 19;443(7113):787-95 – reference: 20699416 - Diabetes. 2010 Nov;59(11):2809-16 – reference: 23258413 - Science. 2013 Feb 15;339(6121):786-91 – reference: 20034597 - Mitochondrion. 2010 Apr;10(3):253-62 – reference: 24746805 - Cell Metab. 2014 Jun 3;19(6):967-80 – reference: 25739441 - J Biol Chem. 2015 Apr 17;290(16):10143-8 – reference: 14717589 - Biochemistry. 2004 Jan 20;43(2):352-61 – reference: 15607001 - Hum Genomics. 2004 Nov;1(6):460-4 – reference: 25786173 - Immunity. 2015 Mar 17;42(3):406-17 – reference: 25525874 - Cell. 2014 Dec 18;159(7):1549-62 – reference: 26498951 - Protein Cell. 2016 Jan;7(1):11-6 – reference: 26223655 - J Immunol. 2015 Sep 1;195(5):1939-43 – reference: 26993045 - J Mol Cell Biol. 2016 Apr;8(2):120-8 – reference: 21633179 - J Clin Invest. 2011 Jun;121(6):2111-7 – reference: 23454757 - J Clin Invest. 2013 Mar;123(3):951-7 – reference: 22342844 - Immunity. 2012 Mar 23;36(3):401-14 – reference: 26993047 - J Mol Cell Biol. 2016 Apr;8(2):93-100 – reference: 23333405 - Mitochondrion. 2013 Mar;13(2):106-18 – reference: 8920976 - Biochem J. 1996 Nov 1;319 ( Pt 3):749-54 – reference: 27303815 - Nat Rev Cardiol. 2016 Jun 15;13(7):386-8 – reference: 1883325 - Biochem J. 1991 Aug 15;278 ( Pt 1):137-41 – reference: 15189144 - Annu Rev Biochem. 2004;73:293-320 – reference: 26371324 - Proc Natl Acad Sci U S A. 2015 Oct 20;112(42):E5699-705 |
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| Snippet | Chronic inflammation in adipose tissue plays a key role in obesity-induced insulin resistance. However, the mechanisms underlying obesity-induced inflammation... Activation of the cGAMP-cGAS-STING pathway has recently been shown to mediate virus- or bacteria-induced activation of the innate immune response. Here we... |
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| SubjectTerms | Activation Adipose tissue Biological Sciences Cytosol Deoxyribonucleic acid DNA High fat diet Immunosurveillance Inflammation Insulin Insulin resistance Mitochondria Mitochondrial DNA Obesity Oxidoreductase Proteins |
| Title | DsbA-L prevents obesity-induced inflammation and insulin resistance by suppressing the mtDNA release-activated cGAS-cGAMP-STING pathway |
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