1. Academic Validation
  2. Human milk derived peptide AOPDM1 attenuates obesity by restricting adipogenic differentiation through MAPK signalling

Human milk derived peptide AOPDM1 attenuates obesity by restricting adipogenic differentiation through MAPK signalling

  • Biochim Biophys Acta Gen Subj. 2021 Mar;1865(3):129836. doi: 10.1016/j.bbagen.2020.129836.
Yun Li 1 Xianwei Cui 2 Xing Wang 2 Dan Shen 3 Anwen Yin 1 Lianghui You 2 Juan Wen 2 Chenbo Ji 4 Xirong Guo 5
Affiliations

Affiliations

  • 1 Nanjing Maternal and Child Health Institute, Women's Hospital of Nanjing Medical University (Nanjing Maternity and Child Health Care Hospital), Nanjing 210004, China; Tongren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200336, China.
  • 2 Nanjing Maternal and Child Health Institute, Women's Hospital of Nanjing Medical University (Nanjing Maternity and Child Health Care Hospital), Nanjing 210004, China.
  • 3 Tongren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200336, China.
  • 4 Nanjing Maternal and Child Health Institute, Women's Hospital of Nanjing Medical University (Nanjing Maternity and Child Health Care Hospital), Nanjing 210004, China. Electronic address: chenboji@njmu.edu.cn.
  • 5 Nanjing Maternal and Child Health Institute, Women's Hospital of Nanjing Medical University (Nanjing Maternity and Child Health Care Hospital), Nanjing 210004, China; Tongren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200336, China. Electronic address: xrguo@shsmu.edu.cn.
Abstract

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 PPARγ 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.

Keywords

Adipocyte differentiation; Breast milk; MAPK pathway; Obesity; Peptide.

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