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Overexpression of Human NPY or AgRP in the Paraventricular Nucleus Increases Feeding and Bodyweight in Young Rhesus Macaques

25 Pages Posted: 20 Feb 2019

See all articles by Tao Zhou

Tao Zhou

ShanghaiTech University - School of Life Science and Technology

Ke Tang

Guangzhou University, School of Life Sciences, Precise Genome Engineering Center

Zhengwu Wang

Sichuan Hengshu Bio-Technology Co., Ltd.

Zun-Fu Ke

Sun Yat-sen University (SYSU) - Molecular Diagnosis and Gene Testing Center

Fan Huang

Government of the People's Republic of China, People's Liberation Army (PLA), First People’s Hospital of Yibin

Ruizhi Tan

Southwest Medical University, Affiliated Traditional Medicine Hospital, Research Center of Integrated Chinese and Western Medicine

Liufang Yin

Shanghai University of Traditional Chinese Medicine - Drug Discovery Lab

Hongli Li

Shanghai University of Traditional Chinese Medicine - Drug Discovery Lab

Shengjie Fan

Shanghai University of Traditional Chinese Medicine - Drug Discovery Lab

Xu Luo

Sichuan Hengshu Bio-Technology Co., Ltd.

Xujiao Ling

Sichuan Hengshu Bio-Technology Co., Ltd.

Xuliang Zhang

ShanghaiTech University - School of Life Science and Technology

Li Wang

Southwest Medical University, Affiliated Traditional Medicine Hospital, Research Center of Integrated Chinese and Western Medicine

Xudong Zhao

Chinese Academy of Sciences (CAS), Kunming Institute of Zoology, Kunming Primate Research Center

Shubin Hong

Sun Yat-sen University (SYSU) - Institute of Precision Medicine

Sui Peng

Sun Yat-Sen University (SYSU), First Affiliated Hospital, Clinical Trial Unit; Sun Yat-sen University (SYSU) - Department of Gastroenterology and Hepatology

Qingchun Tong

University of Texas at Houston, McGovern Medical School, Graduate School of Biological Sciences, Brown Foundation Institute of Molecular Medicine and Program in Neuroscience

Xingxu Huang

ShanghaiTech University - School of Life Science and Technology

Junming Fan

ShanghaiTech University - School of Life Science and Technology

Haipeng Xiao

Sun Yat-sen University (SYSU) - Institute of Precision Medicine; Sun Yat-sen University (SYSU) - Department of Endocrinology

Cheng Huang

Shanghai University of Traditional Chinese Medicine - Drug Discovery Lab

More...

Abstract

Background: The roles of neuropeptides agouti-related peptide (AgRP) and neuropeptide Y (NPY) in feeding behavior regulation have been extensively studied in rodents. However, the biological functions of these peptides in primates are not fully addressed.  

Methods: Lenti-virus mediated expression of human NPY (hNPY) or human AgRP (hAgRP) in paraventricular nucleus (PVN) of the hypothalamus to establish obesity model in monkeys.  

Findings: The feeding behavior and bodyweight were significantly increased in transgenic Rhesus Macaques. Whereas, the blood level of glucose and insulin, as well as metabolic parameters, including blood levels of triglyceride (TG), total cholesterol (TC), high-density lipoprotein-cholesterol (HDL-c), low-density lipoprotein-cholesterol (LDL-c), non-esterified free fatty acids (NEFA) and leptin remained unchanged after virus injection.  

Interpretation: These results have recapitulated some parts of previous reports in rodents, and suggest that these non-germline genetically modified monkeys may provide new models for studying feeding behaviors and related disease, such as obesity and diabetes.  

Funding Statement: This study was supported by the National Natural Science Foundation of China (81671516 to X. Huang) and National Key R&D Program of China (2016YFC0905901 to X. Huang). Xingxu Huang is sponsored by Startup Foundation of ShanghaiTech University.  

Declaration of Interests: All authors have no competing interests to declare, financial or otherwise.

Ethics Approval Statement: The use and care of animals complied with the guideline of the biomedical research ethics committee at the Shanghai University of Traditional Chinese Medicine. The experimental procedures were approved by the Sichuan Hengshu Bio-Tech Co., Ltd animal care and use committee.

Keywords: monkey; agouti-related peptide; neuropeptide Y; feeding behavior; obesity; hypothalamus

Suggested Citation

Zhou, Tao and Tang, Ke and Wang, Zhengwu and Ke, Zun-Fu and Huang, Fan and Tan, Ruizhi and Yin, Liufang and Li, Hongli and Fan, Shengjie and Luo, Xu and Ling, Xujiao and Zhang, Xuliang and Wang, Li and Zhao, Xudong and Hong, Shubin and Peng, Sui and Tong, Qingchun and Huang, Xingxu and Fan, Junming and Xiao, Haipeng and Xiao, Haipeng and Huang, Cheng, Overexpression of Human NPY or AgRP in the Paraventricular Nucleus Increases Feeding and Bodyweight in Young Rhesus Macaques (02/14/2019 00:40:55). Available at SSRN: https://ssrn.com/abstract=3335855 or http://dx.doi.org/10.2139/ssrn.3335855

Tao Zhou

ShanghaiTech University - School of Life Science and Technology

100 Haike Road, Zhangjiang Hi-Tech Park, Pudong
Research Building
Shanghai, 201210
China

Ke Tang

Guangzhou University, School of Life Sciences, Precise Genome Engineering Center

Waihuanxi Road 230
Guangzhou
China

Zhengwu Wang

Sichuan Hengshu Bio-Technology Co., Ltd.

Yibin 644000
Sichuan
China

Zun-Fu Ke

Sun Yat-sen University (SYSU) - Molecular Diagnosis and Gene Testing Center ( email )

Guangzhou, Guangdong
China

Fan Huang

Government of the People's Republic of China, People's Liberation Army (PLA), First People’s Hospital of Yibin

Yibin 64400
Sichuan
China

Ruizhi Tan

Southwest Medical University, Affiliated Traditional Medicine Hospital, Research Center of Integrated Chinese and Western Medicine

Luzhou 646000
Sichuan
China

Liufang Yin

Shanghai University of Traditional Chinese Medicine - Drug Discovery Lab

Shanghai, 201210
China

Hongli Li

Shanghai University of Traditional Chinese Medicine - Drug Discovery Lab

Shanghai, 201210
China

Shengjie Fan

Shanghai University of Traditional Chinese Medicine - Drug Discovery Lab

Shanghai, 201210
China

Xu Luo

Sichuan Hengshu Bio-Technology Co., Ltd.

Yibin 644000
Sichuan
China

Xujiao Ling

Sichuan Hengshu Bio-Technology Co., Ltd.

Yibin 644000
Sichuan
China

Xuliang Zhang

ShanghaiTech University - School of Life Science and Technology

100 Haike Road, Zhangjiang Hi-Tech Park, Pudong
Research Building
Shanghai, 201210
China

Li Wang

Southwest Medical University, Affiliated Traditional Medicine Hospital, Research Center of Integrated Chinese and Western Medicine

Luzhou 646000
Sichuan
China

Xudong Zhao

Chinese Academy of Sciences (CAS), Kunming Institute of Zoology, Kunming Primate Research Center

No.32 Jiaochang Donglu
Kunming, Yunnan 650223
China

Shubin Hong

Sun Yat-sen University (SYSU) - Institute of Precision Medicine

Guangzhou, Guangdong
China

Sui Peng

Sun Yat-Sen University (SYSU), First Affiliated Hospital, Clinical Trial Unit ( email )

China

Sun Yat-sen University (SYSU) - Department of Gastroenterology and Hepatology

135, Xingang Xi Road
Guangdong, Guangdong 510275
China

Qingchun Tong

University of Texas at Houston, McGovern Medical School, Graduate School of Biological Sciences, Brown Foundation Institute of Molecular Medicine and Program in Neuroscience

Houston, TX
United States

Xingxu Huang

ShanghaiTech University - School of Life Science and Technology

100 Haike Road, Zhangjiang Hi-Tech Park, Pudong
Research Building
Shanghai, 201210
China

Junming Fan

ShanghaiTech University - School of Life Science and Technology ( email )

100 Haike Road, Zhangjiang Hi-Tech Park, Pudong
Research Building
Shanghai, 201210
China

Haipeng Xiao

Sun Yat-sen University (SYSU) - Institute of Precision Medicine ( email )

Guangzhou, Guangdong
China

Sun Yat-sen University (SYSU) - Department of Endocrinology ( email )

Guangzhou
China

Cheng Huang (Contact Author)

Shanghai University of Traditional Chinese Medicine - Drug Discovery Lab ( email )

Shanghai, 201210
China