| Title | Adrenomedullin 2 Improves Early Obesity-Induced Adipose Insulin Resistance by Inhibiting the Class II MHC in Adipocytes |
| Authors | Zhang, Song-Yang Lv, Ying Zhang, Heng Gao, Song Wang, Ting Feng, Juan Wang, Yuhui Liu, George Xu, Ming-Jiang Wang, Xian Jiang, Changtao |
| Affiliation | Peking Univ, Key Lab Mol Cardiovasc, Sch Basic Med Sci, Dept Physiol & Pathophysiol,Minist Educ, Beijing, Peoples R China. Beijing Key Lab Cardiovasc Receptors Res, Beijing, Peoples R China. Capital Med Univ, Beijing Chao Yang Hosp, Dept Endocrinol, Beijing, Peoples R China. Peking Univ, Dept Gen Surg, Hosp 1, Beijing, Peoples R China. Peking Univ, Inst Cardiovasc Sci, Key Lab Mol Cardiovasc Sci, Minist Educ, Beijing, Peoples R China. Peking Univ, Key Lab Mol Cardiovasc, Sch Basic Med Sci, Dept Physiol & Pathophysiol,Minist Educ, Beijing, Peoples R China. Wang, X Jiang, CT (reprint author), Beijing Key Lab Cardiovasc Receptors Res, Beijing, Peoples R China. |
| Keywords | GENE-RELATED PEPTIDE CD4(+) T-CELLS ENDOPLASMIC-RETICULUM STRESS ANTIGEN-PRESENTING CELLS DIET-INDUCED OBESITY DENDRITIC CELLS TISSUE INFLAMMATION TGF-BETA EXPRESSION INTERMEDIN |
| Issue Date | 2016 |
| Publisher | DIABETES |
| Citation | DIABETES.2016,65(8),2342-2355. |
| Abstract | MHC class II (MHCII) antigen presentation in adipocytes was reported to trigger early adipose inflammation and insulin resistance. However, the benefits of MHCII inhibition in adipocytes remain largely unknown. Here, we showed that human plasma polypeptide adrenomedullin 2 (ADM2) levels were negatively correlated with HOMA of insulin resistance in obese human. Adipose-specific human ADM2 transgenic (aADM2-tg) mice were generated. The aADM2-tg mice displayed improvements in high-fat diet-induced early adipose insulin resistance. This was associated with increased insulin signaling and decreased systemic inflammation. ADM2 dose-dependently inhibited CIITA-induced MHCII expression by increasing Blimp1 expression in a CRLR/RAMP1-cAMP-dependent manner in cultured adipocytes. Furthermore, ADM2 treatment restored the high-fat diet-induced early insulin resistance in adipose tissue, mainly via inhibition of adipocyte MHCII antigen presentation and CD4(+) T-cell activation. This study demonstrates that ADM2 is a promising candidate for the treatment of early obesity-induced insulin resistance. |
| URI | http://hdl.handle.net/20.500.11897/433645 |
| ISSN | 0012-1797 |
| DOI | 10.2337/db15-1626 |
| Indexed | SCI(E) PubMed |
| Appears in Collections: | 分子心血管学教育部重点实验室 第一医院 基础医学院 |
