Mitophagy-mediated adipose inflammation contributes to type 2 diabetes with hepatic insulin resistance
White adipose tissues (WAT) play crucial roles in maintaining whole-body energy homeostasis, and their dysfunction can contribute to hepatic insulin resistance and type 2 diabetes mellitus (T2DM). However, the mechanisms underlying these alterations remain unknown. By analyzing the transcriptome lan...
Saved in:
| Published in | The Journal of experimental medicine Vol. 218; no. 3 |
|---|---|
| Main Authors | , , , , , , , |
| Format | Journal Article |
| Language | English |
| Published |
United States
Rockefeller University Press
01.03.2021
|
| Subjects | |
| Online Access | Get full text |
Cover
Loading…
| Abstract | White adipose tissues (WAT) play crucial roles in maintaining whole-body energy homeostasis, and their dysfunction can contribute to hepatic insulin resistance and type 2 diabetes mellitus (T2DM). However, the mechanisms underlying these alterations remain unknown. By analyzing the transcriptome landscape in human adipocytes based on available RNA-seq datasets from lean, obese, and T2DM patients, we reveal elevated mitochondrial reactive oxygen species (ROS) pathway and NF-κB signaling with altered fatty acid metabolism in T2DM adipocytes. Mice with adipose-specific deletion of mitochondrial redox Trx2 develop hyperglycemia, hepatic insulin resistance, and hepatic steatosis. Trx2-deficient WAT exhibited excessive mitophagy, increased inflammation, and lipolysis. Mechanistically, mitophagy was induced through increasing ROS generation and NF-κB–dependent accumulation of autophagy receptor p62/SQSTM1, which recruits damaged mitochondria with polyubiquitin chains. Importantly, administration of ROS scavenger or NF-κB inhibitor ameliorates glucose and lipid metabolic disorders and T2DM progression in mice. Taken together, this study reveals a previously unrecognized mechanism linking mitophagy-mediated adipose inflammation to T2DM with hepatic insulin resistance. |
|---|---|
| AbstractList | Adipose-specific deletion of mitochondrial redox
Trx2
induces excessive mitophagy in white adipose tissue with increased inflammation and increased lipolysis, promoting hepatic glucose production and development of T2DM with hepatic steatosis. Administration of NF-κB inhibitor prevents adipose mitophagy and ameliorates T2DM progression.
White adipose tissues (WAT) play crucial roles in maintaining whole-body energy homeostasis, and their dysfunction can contribute to hepatic insulin resistance and type 2 diabetes mellitus (T2DM). However, the mechanisms underlying these alterations remain unknown. By analyzing the transcriptome landscape in human adipocytes based on available RNA-seq datasets from lean, obese, and T2DM patients, we reveal elevated mitochondrial reactive oxygen species (ROS) pathway and NF-κB signaling with altered fatty acid metabolism in T2DM adipocytes. Mice with adipose-specific deletion of mitochondrial redox
Trx2
develop hyperglycemia, hepatic insulin resistance, and hepatic steatosis.
Trx2
-deficient WAT exhibited excessive mitophagy, increased inflammation, and lipolysis. Mechanistically, mitophagy was induced through increasing ROS generation and NF-κB–dependent accumulation of autophagy receptor p62/SQSTM1, which recruits damaged mitochondria with polyubiquitin chains. Importantly, administration of ROS scavenger or NF-κB inhibitor ameliorates glucose and lipid metabolic disorders and T2DM progression in mice. Taken together, this study reveals a previously unrecognized mechanism linking mitophagy-mediated adipose inflammation to T2DM with hepatic insulin resistance. White adipose tissues (WAT) play crucial roles in maintaining whole-body energy homeostasis, and their dysfunction can contribute to hepatic insulin resistance and type 2 diabetes mellitus (T2DM). However, the mechanisms underlying these alterations remain unknown. By analyzing the transcriptome landscape in human adipocytes based on available RNA-seq datasets from lean, obese, and T2DM patients, we reveal elevated mitochondrial reactive oxygen species (ROS) pathway and NF-κB signaling with altered fatty acid metabolism in T2DM adipocytes. Mice with adipose-specific deletion of mitochondrial redox Trx2 develop hyperglycemia, hepatic insulin resistance, and hepatic steatosis. Trx2-deficient WAT exhibited excessive mitophagy, increased inflammation, and lipolysis. Mechanistically, mitophagy was induced through increasing ROS generation and NF-κB-dependent accumulation of autophagy receptor p62/SQSTM1, which recruits damaged mitochondria with polyubiquitin chains. Importantly, administration of ROS scavenger or NF-κB inhibitor ameliorates glucose and lipid metabolic disorders and T2DM progression in mice. Taken together, this study reveals a previously unrecognized mechanism linking mitophagy-mediated adipose inflammation to T2DM with hepatic insulin resistance. White adipose tissues (WAT) play crucial roles in maintaining whole-body energy homeostasis, and their dysfunction can contribute to hepatic insulin resistance and type 2 diabetes mellitus (T2DM). However, the mechanisms underlying these alterations remain unknown. By analyzing the transcriptome landscape in human adipocytes based on available RNA-seq datasets from lean, obese, and T2DM patients, we reveal elevated mitochondrial reactive oxygen species (ROS) pathway and NF-κB signaling with altered fatty acid metabolism in T2DM adipocytes. Mice with adipose-specific deletion of mitochondrial redox Trx2 develop hyperglycemia, hepatic insulin resistance, and hepatic steatosis. Trx2-deficient WAT exhibited excessive mitophagy, increased inflammation, and lipolysis. Mechanistically, mitophagy was induced through increasing ROS generation and NF-κB-dependent accumulation of autophagy receptor p62/SQSTM1, which recruits damaged mitochondria with polyubiquitin chains. Importantly, administration of ROS scavenger or NF-κB inhibitor ameliorates glucose and lipid metabolic disorders and T2DM progression in mice. Taken together, this study reveals a previously unrecognized mechanism linking mitophagy-mediated adipose inflammation to T2DM with hepatic insulin resistance.White adipose tissues (WAT) play crucial roles in maintaining whole-body energy homeostasis, and their dysfunction can contribute to hepatic insulin resistance and type 2 diabetes mellitus (T2DM). However, the mechanisms underlying these alterations remain unknown. By analyzing the transcriptome landscape in human adipocytes based on available RNA-seq datasets from lean, obese, and T2DM patients, we reveal elevated mitochondrial reactive oxygen species (ROS) pathway and NF-κB signaling with altered fatty acid metabolism in T2DM adipocytes. Mice with adipose-specific deletion of mitochondrial redox Trx2 develop hyperglycemia, hepatic insulin resistance, and hepatic steatosis. Trx2-deficient WAT exhibited excessive mitophagy, increased inflammation, and lipolysis. Mechanistically, mitophagy was induced through increasing ROS generation and NF-κB-dependent accumulation of autophagy receptor p62/SQSTM1, which recruits damaged mitochondria with polyubiquitin chains. Importantly, administration of ROS scavenger or NF-κB inhibitor ameliorates glucose and lipid metabolic disorders and T2DM progression in mice. Taken together, this study reveals a previously unrecognized mechanism linking mitophagy-mediated adipose inflammation to T2DM with hepatic insulin resistance. |
| Author | Zhang, Haifeng Shulman, Gerald I. Min, Wang Perry, Rachel J. Zhou, Huanjiao Jenny He, Feng Song, Zhi Huang, Yanrui |
| AuthorAffiliation | 3 Department of Internal Medicine, Yale School of Medicine, New Haven, CT 1 Department of Pathology, Yale School of Medicine, New Haven, CT 2 Department of Cellular and Molecular Physiology, Yale School of Medicine, New Haven, CT |
| AuthorAffiliation_xml | – name: 3 Department of Internal Medicine, Yale School of Medicine, New Haven, CT – name: 2 Department of Cellular and Molecular Physiology, Yale School of Medicine, New Haven, CT – name: 1 Department of Pathology, Yale School of Medicine, New Haven, CT |
| Author_xml | – sequence: 1 givenname: Feng orcidid: 0000-0003-3207-1295 surname: He fullname: He, Feng – sequence: 2 givenname: Yanrui orcidid: 0000-0001-5147-1302 surname: Huang fullname: Huang, Yanrui – sequence: 3 givenname: Zhi orcidid: 0000-0003-3742-0570 surname: Song fullname: Song, Zhi – sequence: 4 givenname: Huanjiao Jenny orcidid: 0000-0003-3071-9473 surname: Zhou fullname: Zhou, Huanjiao Jenny – sequence: 5 givenname: Haifeng orcidid: 0000-0001-9141-7458 surname: Zhang fullname: Zhang, Haifeng – sequence: 6 givenname: Rachel J. orcidid: 0000-0003-0748-8064 surname: Perry fullname: Perry, Rachel J. – sequence: 7 givenname: Gerald I. orcidid: 0000-0003-1529-5668 surname: Shulman fullname: Shulman, Gerald I. – sequence: 8 givenname: Wang orcidid: 0000-0002-2479-6096 surname: Min fullname: Min, Wang |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/33315085$$D View this record in MEDLINE/PubMed |
| BookMark | eNptkUtP3DAUha0KVAboruvKyy4a8Dv2BqlCfSCB2MDacjw3jFFih9hpNf--nvJQi1hZsr9zzvW5h2gvpggIfaTkhBItTu9hPGGEESqoeodWVArSGMn1HloRwlhDCWkP0GHO96QyQqr36IBzTiXRcoX6q1DStHF322aEdXAF1titw5Qy4BD7wY2jKyFF7FMsc-iWAhmXhMt2AsxwVXSwu_odygZvYKqwr8K8DCHiGXLIxUUPx2i_d0OGD0_nEbr9_u3m_Gdzef3j4vzrZeO5FqXR2jAnSQ-94J2k3BmlveIKuO7atfS-d4ZrMG2rlZKSE2iJ6QQYpzrqwfAjdPboOy1d_Y-HOrQb7DSH0c1bm1yw_7_EsLF36ZdtDWsFZ9Xg85PBnB4WyMWOIXsYBhchLdky0dZWlRK7rE__Zr2EPJdbgS-PgJ9TzjP0Lwgldrc7W3dnn3dXcfYK96H8Lb9OGoa3RX8AKAufJg |
| CitedBy_id | crossref_primary_10_1016_j_phrs_2022_106072 crossref_primary_10_3389_fnut_2022_1087826 crossref_primary_10_1016_j_ecoenv_2024_116954 crossref_primary_10_1038_s41598_025_92716_z crossref_primary_10_1080_13813455_2024_2387693 crossref_primary_10_18632_aging_205192 crossref_primary_10_3390_ijms25031504 crossref_primary_10_3390_ijms22136733 crossref_primary_10_31083_j_fbl2812365 crossref_primary_10_3390_plants11131715 crossref_primary_10_1016_j_jhazmat_2023_131750 crossref_primary_10_1016_j_lfs_2022_121162 crossref_primary_10_3390_ijms241210409 crossref_primary_10_3389_fcell_2021_682947 crossref_primary_10_3390_cells12091223 crossref_primary_10_1016_j_biopha_2024_116807 crossref_primary_10_1111_jch_14650 crossref_primary_10_1016_j_mam_2021_100966 crossref_primary_10_3389_fmed_2025_1555077 crossref_primary_10_3390_toxins15030179 crossref_primary_10_3389_fcell_2025_1465092 crossref_primary_10_1111_bph_16103 crossref_primary_10_4049_jimmunol_2200601 crossref_primary_10_12677_ACM_2023_131123 crossref_primary_10_3390_ijms241813762 crossref_primary_10_18632_aging_205075 crossref_primary_10_1016_j_jgg_2022_01_006 crossref_primary_10_1152_ajpendo_00218_2022 crossref_primary_10_32604_biocell_2024_056272 crossref_primary_10_3389_fcvm_2022_917135 crossref_primary_10_1016_j_sjbs_2022_103434 crossref_primary_10_3389_fphar_2023_1149809 crossref_primary_10_1016_j_mtbio_2025_101685 crossref_primary_10_1016_j_phrs_2023_106820 crossref_primary_10_1515_biol_2022_0648 crossref_primary_10_1155_2024_2298306 crossref_primary_10_3164_jcbn_23_1 crossref_primary_10_1084_jem_20210252 crossref_primary_10_1142_S0192415X23500581 crossref_primary_10_1186_s12951_024_02478_5 crossref_primary_10_1016_j_phymed_2023_154943 crossref_primary_10_3389_fimmu_2025_1506500 crossref_primary_10_1016_j_biomaterials_2021_121183 crossref_primary_10_1016_j_ijbiomac_2024_134448 crossref_primary_10_3389_fendo_2022_869951 crossref_primary_10_3390_cells12060947 crossref_primary_10_2174_1871530323666230627121700 crossref_primary_10_1016_j_biopha_2024_116428 crossref_primary_10_3390_ijms232415753 crossref_primary_10_1016_j_csbj_2023_03_017 crossref_primary_10_3390_nu16223878 crossref_primary_10_1016_j_joca_2024_09_013 crossref_primary_10_1038_s41467_022_35262_w crossref_primary_10_3390_biology12091166 crossref_primary_10_12677_ACM_2023_13102265 crossref_primary_10_3389_fphar_2023_1188829 crossref_primary_10_1016_j_foodres_2025_115940 crossref_primary_10_1002_fsn3_4266 crossref_primary_10_1111_obr_13724 crossref_primary_10_1016_j_heliyon_2024_e26791 crossref_primary_10_3389_fphar_2022_864088 crossref_primary_10_1002_oby_23805 crossref_primary_10_1016_j_cellsig_2024_111229 crossref_primary_10_1016_j_mcpro_2023_100508 crossref_primary_10_1002_1873_3468_14877 crossref_primary_10_1016_j_prmcm_2024_100471 crossref_primary_10_3390_nu13093015 crossref_primary_10_1016_j_ecoenv_2022_114075 crossref_primary_10_1016_j_jff_2022_105348 crossref_primary_10_1038_s41574_023_00898_1 crossref_primary_10_3390_diagnostics14111119 crossref_primary_10_3389_fonc_2021_638701 crossref_primary_10_3389_fphar_2023_1253572 crossref_primary_10_1111_1753_0407_13510 crossref_primary_10_1016_j_biopha_2024_116755 crossref_primary_10_1016_j_bioactmat_2024_11_023 crossref_primary_10_1089_ars_2022_0016 crossref_primary_10_1021_acs_jafc_4c05431 crossref_primary_10_1172_JCI148852 crossref_primary_10_3390_ijms24065999 crossref_primary_10_3390_nu14142782 crossref_primary_10_1007_s11010_023_04736_w crossref_primary_10_1016_j_ecoenv_2021_113018 crossref_primary_10_3389_fcell_2021_699621 crossref_primary_10_1016_j_ijbiomac_2025_140776 crossref_primary_10_3168_jds_2023_23465 crossref_primary_10_1016_j_isci_2024_111519 crossref_primary_10_1080_14728222_2022_2049756 crossref_primary_10_1007_s10557_023_07477_6 crossref_primary_10_1016_j_jhepr_2022_100555 crossref_primary_10_4093_dmj_2023_0213 |
| Cites_doi | 10.1038/nm.3084 10.1161/CIRCULATIONAHA.114.012725 10.1016/j.cmet.2016.06.006 10.1038/emboj.2011.25 10.1074/jbc.M304854200 10.1126/science.1184003 10.1038/nri3423 10.1073/pnas.1032913100 10.1172/JCI25102 10.1128/MCB.24.21.9414-9423.2004 10.1128/MCB.25.5.1980-1988.2005 10.1016/j.cell.2015.01.012 10.1074/jbc.275.12.8456 10.1016/j.cmet.2010.03.012 10.1152/physrev.00063.2017 10.1096/fj.14-253971 10.1093/emboj/21.7.1695 10.1128/MCB.23.3.916-922.2003 10.1172/JCI44927 10.1016/j.cmet.2010.12.008 10.1016/j.cell.2015.12.057 10.1038/nm.3615 10.1016/j.tips.2012.03.010 10.1016/j.cmet.2014.12.009 10.1073/pnas.2536828100 10.1038/nature21363 10.1016/j.tem.2012.06.004 10.1038/ncomms9917 10.1016/j.cmet.2017.06.006 10.1210/er.2012-1053 10.1002/hep.26672 10.2337/diabetes.54.5.1392 10.1073/pnas.1423952112 10.4161/auto.6.8.13426 10.1038/ng.3714 10.1016/j.cmet.2017.08.002 10.1172/JCI30400 10.1242/jcs.098475 10.2337/db14-1937 10.1161/CIRCRESAHA.112.268946 10.1016/j.cmet.2015.05.021 10.1056/NEJMra1011035 10.1016/j.molcel.2012.01.008 10.1074/jbc.M111.284612 10.1038/nm1323 10.1038/nm1166 10.1152/ajprenal.00643.2013 10.1038/nrm2391 10.1038/nm.4169 10.1093/nar/20.15.3821 10.1038/cr.2010.178 10.1093/eurheartj/ehn387 10.1172/JCI21752 10.1083/jcb.201409063 10.1038/nature03711 10.1089/ars.2011.4322 10.1089/ars.2007.1586 10.1016/j.cmet.2012.10.016 10.1073/pnas.0906048106 10.1038/ncomms11365 10.1146/annurev.nutr.012809.104747 10.1074/jbc.M115.693523 10.1016/j.molcel.2011.07.039 10.1016/S0891-5849(00)00218-5 10.1210/er.2009-0027 10.1016/j.celrep.2018.10.040 10.1016/j.cell.2018.01.007 10.1038/nri2925 |
| ContentType | Journal Article |
| Copyright | 2020 He et al. 2020 He et al. 2020 |
| Copyright_xml | – notice: 2020 He et al. – notice: 2020 He et al. 2020 |
| DBID | AAYXX CITATION CGR CUY CVF ECM EIF NPM 7X8 5PM |
| DOI | 10.1084/jem.20201416 |
| DatabaseName | CrossRef Medline MEDLINE MEDLINE (Ovid) MEDLINE MEDLINE PubMed MEDLINE - Academic PubMed Central (Full Participant titles) |
| DatabaseTitle | CrossRef MEDLINE Medline Complete MEDLINE with Full Text PubMed MEDLINE (Ovid) MEDLINE - Academic |
| DatabaseTitleList | MEDLINE CrossRef MEDLINE - Academic |
| Database_xml | – sequence: 1 dbid: NPM name: PubMed url: https://proxy.k.utb.cz/login?url=http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed sourceTypes: Index Database – sequence: 2 dbid: EIF name: MEDLINE url: https://proxy.k.utb.cz/login?url=https://www.webofscience.com/wos/medline/basic-search sourceTypes: Index Database |
| DeliveryMethod | fulltext_linktorsrc |
| Discipline | Medicine |
| DocumentTitleAlternate | Adipose mitophagy contributes to T2DM |
| EISSN | 1540-9538 |
| ExternalDocumentID | PMC7927432 33315085 10_1084_jem_20201416 |
| Genre | Research Support, Non-U.S. Gov't Journal Article Research Support, N.I.H., Extramural |
| GrantInformation_xml | – fundername: NHLBI NIH HHS grantid: R01 HL109420 – fundername: NIDDK NIH HHS grantid: R01 DK114793 – fundername: NIDDK NIH HHS grantid: P30 DK034989 – fundername: NHLBI NIH HHS grantid: R01 HL115148 – fundername: NIDDK NIH HHS grantid: R01 DK113984 – fundername: NIDDK NIH HHS grantid: R01 DK116774 – fundername: NCATS NIH HHS grantid: UL1 TR001863 – fundername: NIDDK NIH HHS grantid: RC2 DK120534 – fundername: NIDDK NIH HHS grantid: P30 DK045735 – fundername: ; grantid: R01 HL109420; HL115148; R01 DK113984; R01 DK114793; R01 DK116774; P30 DK045735 – fundername: ; grantid: 19CDA34760284 |
| GroupedDBID | --- -~X 18M 29K 2WC 36B 4.4 53G 5GY 5RE 5VS AAYXX ABOCM ABZEH ACGFO ACNCT ACPRK ADBBV AENEX AFOSN AFRAH ALMA_UNASSIGNED_HOLDINGS AOIJS BAWUL BTFSW C45 CITATION CS3 D-I DIK DU5 E3Z EBS EMB F5P F9R GX1 H13 HYE IH2 KQ8 L7B N9A O5R O5S OK1 P2P P6G R.V RHI SJN TR2 TRP UHB W8F WOQ CGR CUY CVF ECM EIF NPM 7X8 5PM |
| ID | FETCH-LOGICAL-c384t-8892a50fef43b513a968c636e38b7d5ccfa938e9778665530e709b4e9a6b1ce93 |
| ISSN | 0022-1007 1540-9538 |
| IngestDate | Thu Aug 21 18:20:29 EDT 2025 Thu Jul 10 23:35:29 EDT 2025 Sun Jun 15 01:31:06 EDT 2025 Thu Apr 24 22:58:23 EDT 2025 Thu Jul 03 08:35:14 EDT 2025 |
| IsDoiOpenAccess | true |
| IsOpenAccess | true |
| IsPeerReviewed | true |
| IsScholarly | true |
| Issue | 3 |
| Language | English |
| License | 2020 He et al. This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms/). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 International license, as described at https://creativecommons.org/licenses/by-nc-sa/4.0/). |
| LinkModel | OpenURL |
| MergedId | FETCHMERGED-LOGICAL-c384t-8892a50fef43b513a968c636e38b7d5ccfa938e9778665530e709b4e9a6b1ce93 |
| Notes | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 F. He, Y. Huang, Z. Song, and H.J. Zhou contributed equally to this paper. Disclosures: G. Shulman reported grants from NIH (R01 DK119668, R01 DK116774, R01 DK113984, R01 DK114793, RC2 DK120534, and P30 DK045735), Gilead Sciences, Inc., AstraZeneca, and Merck & Co., Inc.; non-financial support from Gilead Sciences, Inc., AstraZeneca, Merck & Co., Inc., Janssen Research & Development, and Novo Nordisk; and personal fees from Gilead Sciences, Inc., AstraZeneca, Merck & Co., Inc., Janssen Research & Development, Novo Nordisk, iMetabolic Biopharma Corp., Maze Therapeutics, Inc., Generian Pharmaceuticals, Ionis Pharmaceuticals, Inc., BridgeBio, Esperion, 89Bio, Inc., Nimbus Discovery, Inc., Staten Biotechnology, Longitude Capital, Celgene Corp., and Aegerion Pharmaceuticals during the conduct of the study. No other disclosures were reported. |
| ORCID | 0000-0001-9141-7458 0000-0003-1529-5668 0000-0003-0748-8064 0000-0002-2479-6096 0000-0003-3742-0570 0000-0001-5147-1302 0000-0003-3207-1295 0000-0003-3071-9473 |
| OpenAccessLink | https://pubmed.ncbi.nlm.nih.gov/PMC7927432 |
| PMID | 33315085 |
| PQID | 2470026649 |
| PQPubID | 23479 |
| ParticipantIDs | pubmedcentral_primary_oai_pubmedcentral_nih_gov_7927432 proquest_miscellaneous_2470026649 pubmed_primary_33315085 crossref_primary_10_1084_jem_20201416 crossref_citationtrail_10_1084_jem_20201416 |
| PublicationCentury | 2000 |
| PublicationDate | 2021-03-01 |
| PublicationDateYYYYMMDD | 2021-03-01 |
| PublicationDate_xml | – month: 03 year: 2021 text: 2021-03-01 day: 01 |
| PublicationDecade | 2020 |
| PublicationPlace | United States |
| PublicationPlace_xml | – name: United States |
| PublicationTitle | The Journal of experimental medicine |
| PublicationTitleAlternate | J Exp Med |
| PublicationYear | 2021 |
| Publisher | Rockefeller University Press |
| Publisher_xml | – name: Rockefeller University Press |
| References | Zhou (2025060211562821100_bib68) 2016; 22 Nonn (2025060211562821100_bib39) 2003; 23 Petersen (2025060211562821100_bib45) 2018; 98 Cai (2025060211562821100_bib7) 2018; 25 Perry (2025060211562821100_bib44) 2015; 160 Vatner (2025060211562821100_bib56) 2015; 112 Jakupoglu (2025060211562821100_bib23) 2005; 25 Shao (2025060211562821100_bib50) 2015; 6 Oral (2025060211562821100_bib40) 2017; 26 Yoshioka (2025060211562821100_bib63) 2012; 122 Narendra (2025060211562821100_bib37) 2010; 6 Huang (2025060211562821100_bib22) 2015; 131 Mottillo (2025060211562821100_bib36) 2016; 24 Lotta (2025060211562821100_bib31) 2017; 49 Shulman (2025060211562821100_bib51) 2014; 371 Janssen-Heininger (2025060211562821100_bib24) 2000; 28 Moon (2025060211562821100_bib34) 2013; 34 Patti (2025060211562821100_bib42) 2010; 31 Heinonen (2025060211562821100_bib19) 2015; 64 Patil (2025060211562821100_bib41) 2014; 306 Kiechl (2025060211562821100_bib26) 2013; 19 He (2025060211562821100_bib18) 2003; 100 Formentini (2025060211562821100_bib14) 2012; 45 Zhong (2025060211562821100_bib67) 2016; 164 Donath (2025060211562821100_bib13) 2011; 11 Kim (2025060211562821100_bib27) 2000; 275 Smith (2025060211562821100_bib52) 2012; 33 Schroder (2025060211562821100_bib49) 2010; 327 Kondegowda (2025060211562821100_bib28) 2015; 22 Tanaka (2025060211562821100_bib54) 2002; 21 Zhao (2025060211562821100_bib66) 2018; 172 Keller (2025060211562821100_bib25) 2010; 30 Patti (2025060211562821100_bib43) 2003; 100 Rutkowski (2025060211562821100_bib46) 2015; 208 Matsumoto (2025060211562821100_bib32) 2011; 44 Chen (2025060211562821100_bib8) 2003; 278 Stanley (2025060211562821100_bib53) 2011; 286 Zhang (2025060211562821100_bib64) 2009; 106 Vernochet (2025060211562821100_bib58) 2014; 28 Matthews (2025060211562821100_bib33) 1992; 20 Wilson-Fritch (2025060211562821100_bib60) 2004; 114 Cypess (2025060211562821100_bib12) 2015; 21 Cai (2025060211562821100_bib6) 2005; 11 Lee (2025060211562821100_bib30) 2013; 18 Birkenfeld (2025060211562821100_bib4) 2014; 59 Galluzzi (2025060211562821100_bib15) 2012; 111 Yang (2025060211562821100_bib62) 2005; 436 Collins (2025060211562821100_bib10) 2016; 291 Yamamoto (2025060211562821100_bib61) 2008; 10 Samuel (2025060211562821100_bib48) 2007; 117 Baker (2025060211562821100_bib2) 2011; 13 Wellen (2025060211562821100_bib59) 2005; 115 Baixauli (2025060211562821100_bib1) 2011; 30 Kusminski (2025060211562821100_bib29) 2012; 23 Morgan (2025060211562821100_bib35) 2011; 21 Herrmann (2025060211562821100_bib20) 2005; 11 Vernochet (2025060211562821100_bib57) 2012; 16 Bi (2025060211562821100_bib3) 2014; 20 Hajer (2025060211562821100_bib17) 2008; 29 Hotamisligil (2025060211562821100_bib21) 2017; 542 Nathan (2025060211562821100_bib38) 2013; 13 Collins (2025060211562821100_bib9) 2012; 125 Tang (2025060211562821100_bib55) 2016; 7 Bogacka (2025060211562821100_bib5) 2005; 54 Conrad (2025060211562821100_bib11) 2004; 24 Guilherme (2025060211562821100_bib16) 2008; 9 Samuel (2025060211562821100_bib47) 2018; 27 Zhang (2025060211562821100_bib65) 2010; 11 40513072 - J Exp Med. 2025 Jul 7;222(7):e2020141606022025c. doi: 10.1084/jem.2020141606022025c. |
| References_xml | – volume: 19 start-page: 358 year: 2013 ident: 2025060211562821100_bib26 article-title: Blockade of receptor activator of nuclear factor-kappaB (RANKL) signaling improves hepatic insulin resistance and prevents development of diabetes mellitus publication-title: Nat. Med. doi: 10.1038/nm.3084 – volume: 131 start-page: 1082 year: 2015 ident: 2025060211562821100_bib22 article-title: Thioredoxin-2 inhibits mitochondrial reactive oxygen species generation and apoptosis stress kinase-1 activity to maintain cardiac function publication-title: Circulation. doi: 10.1161/CIRCULATIONAHA.114.012725 – volume: 24 start-page: 118 year: 2016 ident: 2025060211562821100_bib36 article-title: Lack of Adipocyte AMPK Exacerbates Insulin Resistance and Hepatic Steatosis through Brown and Beige Adipose Tissue Function publication-title: Cell Metab. doi: 10.1016/j.cmet.2016.06.006 – volume: 30 start-page: 1238 year: 2011 ident: 2025060211562821100_bib1 article-title: The mitochondrial fission factor dynamin-related protein 1 modulates T-cell receptor signalling at the immune synapse publication-title: EMBO J. doi: 10.1038/emboj.2011.25 – volume: 278 start-page: 36027 year: 2003 ident: 2025060211562821100_bib8 article-title: Production of reactive oxygen species by mitochondria: central role of complex III publication-title: J. Biol. Chem. doi: 10.1074/jbc.M304854200 – volume: 327 start-page: 296 year: 2010 ident: 2025060211562821100_bib49 article-title: The NLRP3 inflammasome: a sensor for metabolic danger? publication-title: Science. doi: 10.1126/science.1184003 – volume: 13 start-page: 349 year: 2013 ident: 2025060211562821100_bib38 article-title: Beyond oxidative stress: an immunologist’s guide to reactive oxygen species publication-title: Nat. Rev. Immunol. doi: 10.1038/nri3423 – volume: 100 start-page: 8466 year: 2003 ident: 2025060211562821100_bib43 article-title: Coordinated reduction of genes of oxidative metabolism in humans with insulin resistance and diabetes: Potential role of PGC1 and NRF1 publication-title: Proc. Natl. Acad. Sci. USA. doi: 10.1073/pnas.1032913100 – volume: 115 start-page: 1111 year: 2005 ident: 2025060211562821100_bib59 article-title: Inflammation, stress, and diabetes publication-title: J. Clin. Invest. doi: 10.1172/JCI25102 – volume: 24 start-page: 9414 year: 2004 ident: 2025060211562821100_bib11 article-title: Essential role for mitochondrial thioredoxin reductase in hematopoiesis, heart development, and heart function publication-title: Mol. Cell. Biol. doi: 10.1128/MCB.24.21.9414-9423.2004 – volume: 25 start-page: 1980 year: 2005 ident: 2025060211562821100_bib23 article-title: Cytoplasmic thioredoxin reductase is essential for embryogenesis but dispensable for cardiac development publication-title: Mol. Cell. Biol. doi: 10.1128/MCB.25.5.1980-1988.2005 – volume: 160 start-page: 745 year: 2015 ident: 2025060211562821100_bib44 article-title: Hepatic acetyl CoA links adipose tissue inflammation to hepatic insulin resistance and type 2 diabetes publication-title: Cell. doi: 10.1016/j.cell.2015.01.012 – volume: 275 start-page: 8456 year: 2000 ident: 2025060211562821100_bib27 article-title: Mechanism of insulin resistance in A-ZIP/F-1 fatless mice publication-title: J. Biol. Chem. doi: 10.1074/jbc.275.12.8456 – volume: 11 start-page: 402 year: 2010 ident: 2025060211562821100_bib65 article-title: Resistance to high-fat diet-induced obesity and insulin resistance in mice with very long-chain acyl-CoA dehydrogenase deficiency publication-title: Cell Metab. doi: 10.1016/j.cmet.2010.03.012 – volume: 98 start-page: 2133 year: 2018 ident: 2025060211562821100_bib45 article-title: Mechanism of insulin action and insulin resistance publication-title: Physiol. Rev. doi: 10.1152/physrev.00063.2017 – volume: 28 start-page: 4408 year: 2014 ident: 2025060211562821100_bib58 article-title: Adipose tissue mitochondrial dysfunction triggers a lipodystrophic syndrome with insulin resistance, hepatosteatosis, and cardiovascular complications publication-title: FASEB J. doi: 10.1096/fj.14-253971 – volume: 21 start-page: 1695 year: 2002 ident: 2025060211562821100_bib54 article-title: Thioredoxin-2 (TRX-2) is an essential gene regulating mitochondria-dependent apoptosis publication-title: EMBO J. doi: 10.1093/emboj/21.7.1695 – volume: 23 start-page: 916 year: 2003 ident: 2025060211562821100_bib39 article-title: The absence of mitochondrial thioredoxin 2 causes massive apoptosis, exencephaly, and early embryonic lethality in homozygous mice publication-title: Mol. Cell. Biol. doi: 10.1128/MCB.23.3.916-922.2003 – volume: 122 start-page: 267 year: 2012 ident: 2025060211562821100_bib63 article-title: Deletion of thioredoxin-interacting protein in mice impairs mitochondrial function but protects the myocardium from ischemia-reperfusion injury publication-title: J. Clin. Invest. doi: 10.1172/JCI44927 – volume: 13 start-page: 11 year: 2011 ident: 2025060211562821100_bib2 article-title: NF-kappaB, inflammation, and metabolic disease publication-title: Cell Metab. doi: 10.1016/j.cmet.2010.12.008 – volume: 164 start-page: 896 year: 2016 ident: 2025060211562821100_bib67 article-title: NF-kappaB Restricts Inflammasome Activation via Elimination of Damaged Mitochondria publication-title: Cell. doi: 10.1016/j.cell.2015.12.057 – volume: 20 start-page: 911 year: 2014 ident: 2025060211562821100_bib3 article-title: Inhibition of Notch signaling promotes browning of white adipose tissue and ameliorates obesity publication-title: Nat. Med. doi: 10.1038/nm.3615 – volume: 33 start-page: 341 year: 2012 ident: 2025060211562821100_bib52 article-title: Mitochondrial pharmacology publication-title: Trends Pharmacol. Sci. doi: 10.1016/j.tips.2012.03.010 – volume: 21 start-page: 33 year: 2015 ident: 2025060211562821100_bib12 article-title: Activation of human brown adipose tissue by a beta3-adrenergic receptor agonist publication-title: Cell Metab. doi: 10.1016/j.cmet.2014.12.009 – volume: 100 start-page: 15712 year: 2003 ident: 2025060211562821100_bib18 article-title: Adipose-specific peroxisome proliferator-activated receptor gamma knockout causes insulin resistance in fat and liver but not in muscle publication-title: Proc. Natl. Acad. Sci. USA. doi: 10.1073/pnas.2536828100 – volume: 542 start-page: 177 year: 2017 ident: 2025060211562821100_bib21 article-title: Inflammation, metaflammation and immunometabolic disorders publication-title: Nature. doi: 10.1038/nature21363 – volume: 23 start-page: 435 year: 2012 ident: 2025060211562821100_bib29 article-title: Mitochondrial dysfunction in white adipose tissue publication-title: Trends Endocrinol. Metab. doi: 10.1016/j.tem.2012.06.004 – volume: 6 start-page: 8917 year: 2015 ident: 2025060211562821100_bib50 article-title: SENP1-mediated NEMO deSUMOylation in adipocytes limits inflammatory responses and type-1 diabetes progression publication-title: Nat. Commun. doi: 10.1038/ncomms9917 – volume: 26 start-page: 157 year: 2017 ident: 2025060211562821100_bib40 article-title: Inhibition of IKKε and TBK1 Improves Glucose Control in a Subset of Patients with Type 2 Diabetes publication-title: Cell Metab. doi: 10.1016/j.cmet.2017.06.006 – volume: 34 start-page: 377 year: 2013 ident: 2025060211562821100_bib34 article-title: Leptin’s role in lipodystrophic and nonlipodystrophic insulin-resistant and diabetic individuals publication-title: Endocr. Rev. doi: 10.1210/er.2012-1053 – volume: 59 start-page: 713 year: 2014 ident: 2025060211562821100_bib4 article-title: Nonalcoholic fatty liver disease, hepatic insulin resistance, and type 2 diabetes publication-title: Hepatology. doi: 10.1002/hep.26672 – volume: 54 start-page: 1392 year: 2005 ident: 2025060211562821100_bib5 article-title: Pioglitazone induces mitochondrial biogenesis in human subcutaneous adipose tissue in vivo publication-title: Diabetes. doi: 10.2337/diabetes.54.5.1392 – volume: 112 start-page: 1143 year: 2015 ident: 2025060211562821100_bib56 article-title: Insulin-independent regulation of hepatic triglyceride synthesis by fatty acids publication-title: Proc. Natl. Acad. Sci. USA. doi: 10.1073/pnas.1423952112 – volume: 6 start-page: 1090 year: 2010 ident: 2025060211562821100_bib37 article-title: p62/SQSTM1 is required for Parkin-induced mitochondrial clustering but not mitophagy; VDAC1 is dispensable for both publication-title: Autophagy. doi: 10.4161/auto.6.8.13426 – volume: 49 start-page: 17 year: 2017 ident: 2025060211562821100_bib31 article-title: Integrative genomic analysis implicates limited peripheral adipose storage capacity in the pathogenesis of human insulin resistance publication-title: Nat. Genet. doi: 10.1038/ng.3714 – volume: 27 start-page: 22 year: 2018 ident: 2025060211562821100_bib47 article-title: Nonalcoholic Fatty Liver Disease as a Nexus of Metabolic and Hepatic Diseases publication-title: Cell Metab. doi: 10.1016/j.cmet.2017.08.002 – volume: 117 start-page: 739 year: 2007 ident: 2025060211562821100_bib48 article-title: Inhibition of protein kinase Cepsilon prevents hepatic insulin resistance in nonalcoholic fatty liver disease publication-title: J. Clin. Invest. doi: 10.1172/JCI30400 – volume: 125 start-page: 801 year: 2012 ident: 2025060211562821100_bib9 article-title: Mitochondrial redox signalling at a glance publication-title: J. Cell Sci. doi: 10.1242/jcs.098475 – volume: 64 start-page: 3135 year: 2015 ident: 2025060211562821100_bib19 article-title: Impaired Mitochondrial Biogenesis in Adipose Tissue in Acquired Obesity publication-title: Diabetes. doi: 10.2337/db14-1937 – volume: 111 start-page: 1198 year: 2012 ident: 2025060211562821100_bib15 article-title: Mitochondrial control of cellular life, stress, and death publication-title: Circ. Res. doi: 10.1161/CIRCRESAHA.112.268946 – volume: 22 start-page: 77 year: 2015 ident: 2025060211562821100_bib28 article-title: Osteoprotegerin and Denosumab Stimulate Human Beta Cell Proliferation through Inhibition of the Receptor Activator of NF-kappaB Ligand Pathway publication-title: Cell Metab. doi: 10.1016/j.cmet.2015.05.021 – volume: 371 start-page: 1131 year: 2014 ident: 2025060211562821100_bib51 article-title: Ectopic fat in insulin resistance, dyslipidemia, and cardiometabolic disease publication-title: N. Engl. J. Med. doi: 10.1056/NEJMra1011035 – volume: 45 start-page: 731 year: 2012 ident: 2025060211562821100_bib14 article-title: The mitochondrial ATPase inhibitory factor 1 triggers a ROS-mediated retrograde prosurvival and proliferative response publication-title: Mol. Cell. doi: 10.1016/j.molcel.2012.01.008 – volume: 286 start-page: 33669 year: 2011 ident: 2025060211562821100_bib53 article-title: Thioredoxin reductase-2 is essential for keeping low levels of H(2)O(2) emission from isolated heart mitochondria publication-title: J. Biol. Chem. doi: 10.1074/jbc.M111.284612 – volume: 11 start-page: 1322 year: 2005 ident: 2025060211562821100_bib20 article-title: IKK mediates ischemia-induced neuronal death publication-title: Nat. Med. doi: 10.1038/nm1323 – volume: 11 start-page: 183 year: 2005 ident: 2025060211562821100_bib6 article-title: Local and systemic insulin resistance resulting from hepatic activation of IKK-beta and NF-kappaB publication-title: Nat. Med. doi: 10.1038/nm1166 – volume: 306 start-page: F734 year: 2014 ident: 2025060211562821100_bib41 article-title: Inactivation of renal mitochondrial respiratory complexes and manganese superoxide dismutase during sepsis: mitochondria-targeted antioxidant mitigates injury publication-title: Am. J. Physiol. Renal Physiol. doi: 10.1152/ajprenal.00643.2013 – volume: 9 start-page: 367 year: 2008 ident: 2025060211562821100_bib16 article-title: Adipocyte dysfunctions linking obesity to insulin resistance and type 2 diabetes publication-title: Nat. Rev. Mol. Cell Biol. doi: 10.1038/nrm2391 – volume: 22 start-page: 1033 year: 2016 ident: 2025060211562821100_bib68 article-title: Endothelial exocytosis of angiopoietin-2 resulting from CCM3 deficiency contributes to cerebral cavernous malformation publication-title: Nat. Med. doi: 10.1038/nm.4169 – volume: 20 start-page: 3821 year: 1992 ident: 2025060211562821100_bib33 article-title: Thioredoxin regulates the DNA binding activity of NF-χB by reduction of a disulphid bond involving cysteine 62 publication-title: Nucleic Acids Res. doi: 10.1093/nar/20.15.3821 – volume: 21 start-page: 103 year: 2011 ident: 2025060211562821100_bib35 article-title: Crosstalk of reactive oxygen species and NF-kappaB signaling publication-title: Cell Res. doi: 10.1038/cr.2010.178 – volume: 29 start-page: 2959 year: 2008 ident: 2025060211562821100_bib17 article-title: Adipose tissue dysfunction in obesity, diabetes, and vascular diseases publication-title: Eur. Heart J. doi: 10.1093/eurheartj/ehn387 – volume: 114 start-page: 1281 year: 2004 ident: 2025060211562821100_bib60 article-title: Mitochondrial remodeling in adipose tissue associated with obesity and treatment with rosiglitazone publication-title: J. Clin. Invest. doi: 10.1172/JCI21752 – volume: 208 start-page: 501 year: 2015 ident: 2025060211562821100_bib46 article-title: The cell biology of fat expansion publication-title: J. Cell Biol. doi: 10.1083/jcb.201409063 – volume: 436 start-page: 356 year: 2005 ident: 2025060211562821100_bib62 article-title: Serum retinol binding protein 4 contributes to insulin resistance in obesity and type 2 diabetes publication-title: Nature. doi: 10.1038/nature03711 – volume: 18 start-page: 1165 year: 2013 ident: 2025060211562821100_bib30 article-title: Thioredoxin and Thioredoxin Target Proteins: From Molecular Mechanisms to Functional Significance publication-title: Antioxid. Redox Signal. doi: 10.1089/ars.2011.4322 – volume: 10 start-page: 43 year: 2008 ident: 2025060211562821100_bib61 article-title: Transgenic expression of antioxidant protein thioredoxin in pancreatic beta cells prevents progression of type 2 diabetes mellitus publication-title: Antioxid. Redox Signal. doi: 10.1089/ars.2007.1586 – volume: 16 start-page: 765 year: 2012 ident: 2025060211562821100_bib57 article-title: Adipose-specific deletion of TFAM increases mitochondrial oxidation and protects mice against obesity and insulin resistance publication-title: Cell Metab. doi: 10.1016/j.cmet.2012.10.016 – volume: 106 start-page: 19860 year: 2009 ident: 2025060211562821100_bib64 article-title: Adipose-specific deletion of autophagy-related gene 7 (atg7) in mice reveals a role in adipogenesis publication-title: Proc. Natl. Acad. Sci. USA. doi: 10.1073/pnas.0906048106 – volume: 7 start-page: 11365 year: 2016 ident: 2025060211562821100_bib55 article-title: Adipose tissue mTORC2 regulates ChREBP-driven de novo lipogenesis and hepatic glucose metabolism publication-title: Nat. Commun. doi: 10.1038/ncomms11365 – volume: 30 start-page: 341 year: 2010 ident: 2025060211562821100_bib25 article-title: Physiological insights gained from gene expression analysis in obesity and diabetes publication-title: Annu. Rev. Nutr. doi: 10.1146/annurev.nutr.012809.104747 – volume: 291 start-page: 6641 year: 2016 ident: 2025060211562821100_bib10 article-title: Oxidative Stress Promotes Peroxiredoxin Hyperoxidation and Attenuates Pro-survival Signaling in Aging Chondrocytes publication-title: J. Biol. Chem. doi: 10.1074/jbc.M115.693523 – volume: 44 start-page: 279 year: 2011 ident: 2025060211562821100_bib32 article-title: Serine 403 phosphorylation of p62/SQSTM1 regulates selective autophagic clearance of ubiquitinated proteins publication-title: Mol. Cell. doi: 10.1016/j.molcel.2011.07.039 – volume: 28 start-page: 1317 year: 2000 ident: 2025060211562821100_bib24 article-title: Recent advances towards understanding redox mechanisms in the activation of nuclear factor kappaB publication-title: Free Radic. Biol. Med. doi: 10.1016/S0891-5849(00)00218-5 – volume: 31 start-page: 364 year: 2010 ident: 2025060211562821100_bib42 article-title: The role of mitochondria in the pathogenesis of type 2 diabetes publication-title: Endocr. Rev. doi: 10.1210/er.2009-0027 – volume: 25 start-page: 1708 year: 2018 ident: 2025060211562821100_bib7 article-title: Autophagy Ablation in Adipocytes Induces Insulin Resistance and Reveals Roles for Lipid Peroxide and Nrf2 Signaling in Adipose-Liver Crosstalk publication-title: Cell Rep. doi: 10.1016/j.celrep.2018.10.040 – volume: 172 start-page: 731 year: 2018 ident: 2025060211562821100_bib66 article-title: TBK1 at the Crossroads of Inflammation and Energy Homeostasis in Adipose Tissue publication-title: Cell. doi: 10.1016/j.cell.2018.01.007 – volume: 11 start-page: 98 year: 2011 ident: 2025060211562821100_bib13 article-title: Type 2 diabetes as an inflammatory disease publication-title: Nat. Rev. Immunol. doi: 10.1038/nri2925 – reference: 40513072 - J Exp Med. 2025 Jul 7;222(7):e2020141606022025c. doi: 10.1084/jem.2020141606022025c. |
| SSID | ssj0014456 |
| Score | 2.617183 |
| Snippet | White adipose tissues (WAT) play crucial roles in maintaining whole-body energy homeostasis, and their dysfunction can contribute to hepatic insulin resistance... Adipose-specific deletion of mitochondrial redox Trx2 induces excessive mitophagy in white adipose tissue with increased inflammation and increased lipolysis,... |
| SourceID | pubmedcentral proquest pubmed crossref |
| SourceType | Open Access Repository Aggregation Database Index Database Enrichment Source |
| SubjectTerms | Adipocytes - metabolism Adipocytes - ultrastructure Adipose Tissue - pathology Animals Diabetes Mellitus, Type 2 - pathology Diet, High-Fat Energy Metabolism Fatty Liver - pathology Gene Deletion Gene Targeting Gluconeogenesis Homeostasis Humans Hyperglycemia - complications Hyperglycemia - pathology Inflammation - pathology Insulin Resistance Lipogenesis Liver - pathology Male Metabolism Mice Mice, Inbred C57BL Mice, Knockout Mitochondria - metabolism Mitochondria - ultrastructure Mitophagy NF-kappa B - metabolism Oxidative Stress Phenotype Reactive Oxygen Species - metabolism Sequestosome-1 Protein Signal Transduction Thioredoxins - metabolism |
| Title | Mitophagy-mediated adipose inflammation contributes to type 2 diabetes with hepatic insulin resistance |
| URI | https://www.ncbi.nlm.nih.gov/pubmed/33315085 https://www.proquest.com/docview/2470026649 https://pubmed.ncbi.nlm.nih.gov/PMC7927432 |
| Volume | 218 |
| hasFullText | 1 |
| inHoldings | 1 |
| isFullTextHit | |
| isPrint | |
| link | http://utb.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwnV1Nj9MwELWqRVrtBfFN-ZKR4IQCre269hGtgAqpiMOuVPYSOY5Ds4K0Ks1h-S38WGYcJ3FbkGAvVZU6TtX3OuOx38wQ8iLPMmms04nURici5yYxJrOJnWoGDk1yU2Du8PyTnJ2Lj4vJYjD4FamW6m322v78Y17JdVCFa4ArZsn-B7LdpHAB3gO-8AoIw-s_YTwvsSyA-XqV-AQQXDyavFyjBB2mB6ybvMRGj46NrZp6Dvvbrn4vdunWvnhrK06HMByXli0nLntWRWvYnf4A-8f0s0Y57IJv9NwJu9NfTLWpy253J8iCL5bdpYvlqvZeEe64LM3Kq3Cu4i0KFmm0grYJDFKB5xCbg_zH2DZDWIyajcYzBXMsRnjArGJ7zXqD3cbzB35gpAT6AYe1BhhqWWU8DFBcf_ec4JxjQfxJ7w07jeLn-SnyVXBw8DcYBCHYH-PDohMQQSTqewN33zukVcCj38QPPiHH7VN21z4HAc2-Ljda6JzdIjcDuvRtQ7fbZOCqO-R4HsC9S4pD1tHAOhqzjkaso9sVRdZRRlvWUWQdDayjgXW0Z909cv7-3dnpLAndOhLLldgmSmlmJqPCFYJnkzE3WioruXRcZdN8Ym1hNFdOY8FCic2q3HSkM-G0kdkYrAW_T46qVeUeEmrHOUQlrpBKcWFgqkLl2mWaFYJZ8M5D8qr9HVMbStljR5VvqZdUKJECAGkLwJC87EavmxIufxn3vIUkBRuLB2emcqv6R8rEFPcqpNBD8qCBqJupxXZIpjvgdQOwfvvuJ1W59HXcA70eXfvOx-Sk_7s9IUfbTe2ewhp5mz3zVP0NGlrE7Q |
| linkProvider | Geneva Foundation for Medical Education and Research |
| openUrl | ctx_ver=Z39.88-2004&ctx_enc=info%3Aofi%2Fenc%3AUTF-8&rfr_id=info%3Asid%2Fsummon.serialssolutions.com&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Mitophagy-mediated+adipose+inflammation+contributes+to+type+2+diabetes+with+hepatic+insulin+resistance&rft.jtitle=The+Journal+of+experimental+medicine&rft.au=He%2C+Feng&rft.au=Huang%2C+Yanrui&rft.au=Song%2C+Zhi&rft.au=Zhou%2C+Huanjiao+Jenny&rft.date=2021-03-01&rft.pub=Rockefeller+University+Press&rft.issn=0022-1007&rft.eissn=1540-9538&rft.volume=218&rft.issue=3&rft_id=info:doi/10.1084%2Fjem.20201416&rft_id=info%3Apmid%2F33315085&rft.externalDocID=PMC7927432 |
| thumbnail_l | http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/lc.gif&issn=0022-1007&client=summon |
| thumbnail_m | http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/mc.gif&issn=0022-1007&client=summon |
| thumbnail_s | http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/sc.gif&issn=0022-1007&client=summon |