详情页 - 聚合机构库演示平台

当前位置：首页 > 详情页

Antisense oligonucleotide and thyroid hormone conjugates for obesity treatment

68| 认领 | 导出 | 链接全文 |

文献详情

资源类型：

WOS体系：

Pubmed体系：

收录情况： ◇ SCIE

作者：

单位： [1]Department of Medicine, Physiology and Biophysics, UC Irvine Diabetes Center, Center for Epigenetics and Metabolism, University of California Irvine, Irvine, California, 92697, USA. [2]Department of Kinesiology & Physiology, East Carolina Diabetes and Obesity Institute, East Carolina University, Greenville, North Carolina 27834, USA. [3]Japan Society for the Promotion of Science, Tokyo, 1020083, Japan. [4]Department of Geriatrics, the Second Affiliated Hospital, Nanjing Medical University, Nanjing, 211166, China. [5]Department of Geriatrics, Sir Run Run Shaw Hospital, Nanjing Medical University, Nanjing, 211166, China. [6]Medical Metabolomics Center, Jiangsu Key Laboratory of Pediatric Respiratory Disease, Nanjing University of Chinese Medicine, Nanjing, 210023, China. [7]Department of Cardiology, the First Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, 210029, China. [8]Department of Comprehensive Surgery, Medical and Health Center, Beijing Friendship Hospital, Capital Medical University, Beijing, China. [9]Department of Chemistry, University of California, Irvine, 92697, California, USA.

出处：

DOI：

ISSN：

摘要：

Using the principle of antibody-drug conjugates that deliver highly potent cytotoxic agents to cancer cells for cancer therapy, we here report the synthesis of antisense-oligonucleotides (ASO) and thyroid hormone T3 conjugates for obesity treatment. ASOs primarily target fat and liver with poor penetrance to other organs. Pharmacological T3 treatment increases energy expenditure and causes weight loss, but is contraindicated for obesity treatment due to systemic effects on multiple organs. We hypothesize that ASO-T3 conjugates may knock down target genes and enrich T3 action in fat and liver. Two established ASOs are tested. Nicotinamide N-methyltransferase (NNMT)-ASO prevents dietinduced obesity in mice. Apolipoprotein B (ApoB)-ASO is an FDA approved drug for treating familial hypercholesterolemia. NNMT-ASO and ApoB-ASO are chemically conjugated with T3 using a noncleavable sulfo-SMCC linker. Both NNMT-ASO-T3 (NAT3) and ApoB-ASO-T3 (AAT3) enhance thyroid hormone receptor activity. Treating obese mice with NAT3 or AAT3 decreases adiposity and increases lean mass. ASO-T3 enhances white fat browning, decreases genes for fatty acid synthesis in liver, and shows limited effects on T3 target genes in heart and muscle. Furthermore, AAT3 augments LDL cholesterol-lowering effects of ApoB-ASO. Therefore, ASO and hormone/drug conjugation may provide a novel strategy for obesity and hyperlipidemia treatment.

基金：

语种：

被引次数：

WOS：

PubmedID：

中科院(CAS)分区：

出版当年[2016]版：

大类 | 2 区综合性期刊

小类 | 2 区综合性期刊

最新[2025]版：

大类 | 3 区综合性期刊

小类 | 3 区综合性期刊

JCR分区：

出版当年[2015]版：

Q1 MULTIDISCIPLINARY SCIENCES

最新[2023]版：

Q1 MULTIDISCIPLINARY SCIENCES

影响因子： 最新[2023版] 3.8 最新五年平均[2021-2025] 4.3 出版当年[2015版] 5.228 出版当年五年平均[2011-2015] 5.525 出版前一年[2014版] 5.578 出版后一年[2016版] 4.259

第一作者：

第一作者单位： [1]Department of Medicine, Physiology and Biophysics, UC Irvine Diabetes Center, Center for Epigenetics and Metabolism, University of California Irvine, Irvine, California, 92697, USA.

共同第一作者：

通讯作者：

推荐引用方式(GB/T 7714)：

APA：

MLA：