机构:[1]Nanjing Maternal and Child Health Institute, Women’s Hospital of Nanjing Medical University (Nanjing Maternity and Child Health Care Hospital), Nanjing 210004, China[2]Tongren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200336, China
Background: Emerging evidence revealed peptides within breast milk may be an abundant source of potential candidates for metabolism regulation. Our previous work identified numerous peptides existed in breast milk, but its function has not been validated. Thus, our study aims to screen for novel peptides that have the potential to antagonize obesity and diabetes. Methods: A function screen was designed to identify the candidate peptide and then the peptide effect was validated by assessing lipid storage. Afterwards, the in vivo study was performed in two obese models: high-fat diet (HFD)-induced obese mice and obese ob/ob mice. For mechanism study, a RNA-seq analysis was conducted to explore the pathway that account for the biological function of peptide. Results: By performing a small scale screening, a peptide (AVPVQALLLNQ) termed AOPDM1 (anti-obesity peptide derived from breast milk 1) was identified to reduce lipid storage in adipocytes. Further study showed AOPDM1 suppressed adipocyte differentiation by sustaining ERK activity at later stage of differentiation which down-regulated PPAR gamma expression. In vivo, AOPDM1 effectively reduced fat mass and improved glucose metabolism in high-fat diet (HFD)-induced obese mice and obese ob/ob mice. Conclusions: We identified a novel peptide AOPDM1 derived from breast milk could restrict adipocyte differentiation and ameliorate obesity through regulating MAPK pathway. General significance: Our findings may provide a potential candidate for the discovery of therapeutic drugs for obesity and type 2 diabetes.
基金:
National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81700744, 81670773, 81770866, 81770837, 81601333, 81701491]; Jiangsu Provincial Key Research and Development Program [BE2016619, BE2018614, BE2018616]; Nanjing Technological Development Program [201715054, 201803012]; 333 High Level Talents Training Project of Jiangsu Province; Jiangsu Provincial Medical Youth Talent [QNRC2016109, QNRC2016108]; Science and Technology Development Foundation of Nanjing Medical University [2016NJMUZD062, 2016NJMUZD060]; Nanjing Medical Science and Technique Development Foundation [YKK16199, YKK17180]
第一作者机构:[1]Nanjing Maternal and Child Health Institute, Women’s Hospital of Nanjing Medical University (Nanjing Maternity and Child Health Care Hospital), Nanjing 210004, China[2]Tongren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200336, China
共同第一作者:
通讯作者:
通讯机构:[1]Nanjing Maternal and Child Health Institute, Women’s Hospital of Nanjing Medical University (Nanjing Maternity and Child Health Care Hospital), Nanjing 210004, China[2]Tongren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200336, China[*1]Tongren Hospital, Shanghai Jiao Tong University School of Medicine, 1111 XianXia Road, Shanghai 200336, China.
推荐引用方式(GB/T 7714):
Li Yun,Cui Xianwei,Wang Xing,et al.Human milk derived peptide AOPDM1 attenuates obesity by restricting adipogenic differentiation through MAPK signalling[J].BIOCHIMICA ET BIOPHYSICA ACTA-GENERAL SUBJECTS.2021,1865(3):doi:10.1016/j.bbagen.2020.129836.
APA:
Li, Yun,Cui, Xianwei,Wang, Xing,Shen, Dan,Yin, Anwen...&Guo, Xirong.(2021).Human milk derived peptide AOPDM1 attenuates obesity by restricting adipogenic differentiation through MAPK signalling.BIOCHIMICA ET BIOPHYSICA ACTA-GENERAL SUBJECTS,1865,(3)
MLA:
Li, Yun,et al."Human milk derived peptide AOPDM1 attenuates obesity by restricting adipogenic differentiation through MAPK signalling".BIOCHIMICA ET BIOPHYSICA ACTA-GENERAL SUBJECTS 1865..3(2021)