Targeting phospholipid remodeling pathway improves insulin resistance in diabetic mouse models

Author:

Tian Ye1,Lu Wei1,Shi Ruicheng1,McGuffee Reagan2,Lee Richard3,Ford David A.2,Wang Bo145ORCID

Affiliation:

1. Department of Comparative Biosciences, College of Veterinary Medicine University of Illinois at Urbana‐Champaign Urbana Illinois USA

2. Department of Biochemistry and Molecular Biology, and Center for Cardiovascular Research Saint Louis University St. Louis Missouri USA

3. Ionis Pharmaceuticals Carlsbad California USA

4. Division of Nutritional Sciences, College of Agricultural, Consumer and Environmental Sciences University of Illinois at Urbana‐Champaign Urbana Illinois USA

5. Cancer Center at Illinois University of Illinois at Urbana‐Champaign Urbana Illinois USA

Abstract

AbstractPrevious studies have revealed that membrane phospholipid composition controlled by lysophosphatidylcholine acyltransferase 3 (LPCAT3) is involved in the development of insulin resistance in type 2 diabetes. In this study, we aimed to investigate the therapeutic potential of targeting Lpcat3 in the treatment of insulin resistance in diabetic mouse models. Lpcat3 expression was suppressed in the whole body by antisense oligonucleotides (ASO) injection or in the liver by adeno‐associated virus (AAV)‐encoded Cre in high‐fat diet (HFD)‐induced and genetic ob/ob type 2 diabetic mouse models. Glucose tolerance test (GTT), insulin tolerance test (ITT), fasting blood glucose, and insulin levels were used to assess insulin sensitivity. Lipid levels in the liver and serum were measured. The expression of genes involved in de novo lipogenesis was analyzed by real‐time RT‐PCR. Metabolic rates were measured by indirect calorimetry using the Comprehensive Lab Animal Monitoring System (CLAMS). Our data demonstrate that acute knockout of hepatic Lpcat3 by AAV‐Cre improves both hyperglycemia and hypertriglyceridemia in HFD‐fed mice. Similarly, whole‐body ablation of Lpcat3 by ASO administration improves obesity and insulin resistance in both HFD‐fed and ob/ob mice. These findings demonstrate that targeting LPCAT3 could be a novel therapy for insulin resistance.

Funder

National Institute of Diabetes and Digestive and Kidney Diseases

Publisher

Wiley

Subject

Genetics,Molecular Biology,Biochemistry,Biotechnology

Cited by 2 articles. 订阅此论文施引文献 订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献

同舟云学术

1.学者识别学者识别

2.学术分析学术分析

3.人才评估人才评估

"同舟云学术"是以全球学者为主线,采集、加工和组织学术论文而形成的新型学术文献查询和分析系统,可以对全球学者进行文献检索和人才价值评估。用户可以通过关注某些学科领域的顶尖人物而持续追踪该领域的学科进展和研究前沿。经过近期的数据扩容,当前同舟云学术共收录了国内外主流学术期刊6万余种,收集的期刊论文及会议论文总量共计约1.5亿篇,并以每天添加12000余篇中外论文的速度递增。我们也可以为用户提供个性化、定制化的学者数据。欢迎来电咨询!咨询电话:010-8811{复制后删除}0370

www.globalauthorid.com

TOP

Copyright © 2019-2024 北京同舟云网络信息技术有限公司
京公网安备11010802033243号  京ICP备18003416号-3