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Immunotherapy against angiotensin II receptor ameliorated insulin resistance in a leptin receptor-dependent manner.
Zheng, Jiayu; Ding, Jiaxing; Liao, Mengyang; Qiu, Zhihua; Yuan, Qingchen; Mai, Wuqian; Dai, Yong; Zhang, Hongrong; Wu, Hailang; Wang, Yingxuan; Liao, Yuhua; Chen, Xiao; Cheng, Xiang.
Afiliação
  • Zheng J; Department of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
  • Ding J; Key Lab of Molecular Biological Targeted Therapies of the Ministry of Education, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
  • Liao M; Department of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
  • Qiu Z; Key Lab of Molecular Biological Targeted Therapies of the Ministry of Education, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
  • Yuan Q; Department of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
  • Mai W; Key Lab of Molecular Biological Targeted Therapies of the Ministry of Education, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
  • Dai Y; Department of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
  • Zhang H; Key Lab of Molecular Biological Targeted Therapies of the Ministry of Education, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
  • Wu H; Department of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
  • Wang Y; Key Lab of Molecular Biological Targeted Therapies of the Ministry of Education, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
  • Liao Y; Department of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
  • Chen X; Key Lab of Molecular Biological Targeted Therapies of the Ministry of Education, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
  • Cheng X; Department of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
FASEB J ; 35(1): e21157, 2021 01.
Article em En | MEDLINE | ID: mdl-33155736
ABSTRACT
The angiotensin II type 1 receptor (AT1R) signaling pathway is reported to modulate glucose metabolism. Targeting AT1R, our group invented ATRQß-001 vaccine, a novel immunotherapeutic strategy to block the activation of AT1R. Here, we evaluated the therapeutic efficacy of ATRQß-001 vaccine in insulin resistance, and investigated the mechanism. Our results showed that ATRQß-001 vaccine and specific monoclonal antibody against epitope ATR-001 (McAb-ATR) decreased fasting serum insulin concentration and improved glucose and insulin tolerance in ob/ob mice. These beneficial effects were verified in high-fat diet-induced obese mice. McAb-ATR activated insulin signaling in skeletal muscle and insulin-resistant C2C12 myotubes without affecting liver or white adipose tissue of ob/ob mice. Mechanistically, the favorable impact of McAb-ATR on insulin resistance was abolished in db/db mice and in C2C12 myotubes with leptin receptor knockdown. AT1R knockdown also eradicated the effects of McAb-ATR in C2C12 myotubes. Furthermore, McAb-ATR treatment was able to activate the leptin receptor-mediated JAK2/STAT3 signaling in skeletal muscle of ob/ob mice and C2C12 myotubes. Additionally, angiotensin II downregulated the leptin signaling in skeletal muscle of ob/ob and diet-induced obese mice. We demonstrated that ATRQß-001 vaccine and McAb-ATR improved whole-body insulin resistance and regulated glucose metabolism in skeletal muscle in a leptin receptor-dependent manner. Our data suggest that immunotherapy targeting AT1R is a novel strategy for treating insulin resistance.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Resistência à Insulina / Receptores de Angiotensina / Receptores para Leptina / Vacinas de Partículas Semelhantes a Vírus / Imunoterapia Limite: Animals Idioma: En Revista: FASEB J Ano de publicação: 2021 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Resistência à Insulina / Receptores de Angiotensina / Receptores para Leptina / Vacinas de Partículas Semelhantes a Vírus / Imunoterapia Limite: Animals Idioma: En Revista: FASEB J Ano de publicação: 2021 Tipo de documento: Article