MOTS-c peptide regulates adipose homeostasis to prevent ovariectomy-induced metabolic dysfunction

  • Huanyu Lu
  • Ming Wei
  • Yue Zhai
  • Qingyang Li
  • Zichen Ye
  • Li Wang
  • Wenjing Luo
  • Jingyuan ChenEmail author
  • Zifan LuEmail author
Original Article


The postmenopausal state is associated with an increased risk of metabolic disorder including reduced energy expenditure and weight gain, leading to higher cardiovascular and cancer risks among other diseases. Mitochondrial-derived peptide (MOTS-c) is a 16–amino acid peptide encoded by mitochondrial DNA. Here, we showed that MOTS-c treatment in mice prevented ovariectomy-induced obesity and insulin resistance. After ovariectomy, low levels of estrogens increased fat mass overload and disturbed normal adipose function, forcing the development of insulin resistance. MOTS-c treatment increased brown fat activation and reduced OVX-induced fat accumulation and inflammatory invasion in white adipose tissue, which contributes to the lower level of fatty acid in serum and liver. Moreover, MOTS-c activated AMPK pathway to improve energy dissipation and insulin sensitivity. And a blocker of AMPK pathway was found to attenuate the role of MOTS-c in the regulation of adipocyte lipid metabolism. In conclusion, MOTS-c is a high potential candidate for chronic treatment of menopausal induced metabolic dysfunction.

Key messages

• MOTS-c prevents ovariectomy (OVX)-induced body weight gain and insulin resistance.

• MOTS-c reduces fat mass and suppresses inflammatory response under OVX condition.

• MOTS-c sustains the activity of the brown adipose under OVX condition.

• MOTS-c mediates AMPK pathway activation to control adipose metabolic homeostasis.


MOTS-c Ovariectomy Metabolic disorder Adipose AMPK 


Funding information

This research was supported by the National Natural Science Foundation of China (NSF: 31571215; NSF: 31270843, NSF: 81330045; NSF: 81730053) and the Military Logistics Research Project (AWS14L008; AWS16J022).

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Supplementary material

109_2018_1738_MOESM1_ESM.docx (229 kb)
ESM 1 (DOCX 228 kb)


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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  • Huanyu Lu
    • 1
  • Ming Wei
    • 2
  • Yue Zhai
    • 3
  • Qingyang Li
    • 4
  • Zichen Ye
    • 5
  • Li Wang
    • 5
  • Wenjing Luo
    • 1
  • Jingyuan Chen
    • 1
    Email author
  • Zifan Lu
    • 5
    Email author
  1. 1.Department of Occupational and Environmental Health and the Ministry of Education Key Lab of Hazard Assessment and Control in Special Operational Environment, School of Public HealthAir Force Medical UniversityXi’anPeople’s Republic of China
  2. 2.Department of PharmacologyXi’an Medical UniversityXi’anPeople’s Republic of China
  3. 3.Department of Cell BiologyAir Force Medical UniversityXi’anPeople’s Republic of China
  4. 4.Company 22, Brigade 6, School of Basic MedicineAir Force Medical UniversityXi’anPeople’s Republic of China
  5. 5.State Key Laboratory of Cancer Biology, Department of Pharmacogenomics, School of PharmacyAir Force Medical UniversityXi’anPeople’s Republic of China

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