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

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.