Lipids and insulin regulate mitochondrial-derived peptide (MOTS-c) in PCOS and healthy subjects

Manjunath Ramanjaneya, Jayakumar Jerobin, Ilham Bettahi, Milin Bensila, Myint Aye, Kodappully Sivaraman Siveen, Thozhukat Sathyapalan, Monica Skarulis, Abdul Badi Abou-Samra, Stephen Atkin

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Objective: Polycystic ovarian syndrome (PCOS) is a heterogeneous endocrine disorder associated with mitochondrial dysfunction and insulin resistance (IR). MOTS-c, a mitochondrial peptide, promotes insulin sensitivity (IS) through activating AKT and AMPK-dependent pathways. The current study was designed to examine the response of MOTS-c to lipids (intralipid) followed by insulin in PCOS and healthy subjects. Methods: All subjects underwent 5-hour intralipid/saline infusion with a hyperinsulinemic-euglycaemic clamp in the final 2 hours. Plasma samples were collected to measure circulating MOTS-c using a commercial ELISA kit. Subsequently, this was repeated following an eight-week exercise intervention. Results: Intralipid significantly increased plasma MOTS-c both in controls and PCOS subjects, whilst the insulin infusion blunted the intralipid-induced response seen for both lipids and MOT-c. Intralipid elevated plasma MOTS-c to 232 ± 124% of basal in control (P < 0.01) and to 349 ± 206% of basal in PCOS (P < 0.001) subjects. Administration of insulin suppressed intralipid-induced MOTS-c from 232 ± 124% to 165 ± 97% (NS) in control and from 349 ± 206% to 183 ± 177% (P < 0.05) in PCOS subjects, respectively. Following exercise, intralipid elevated plasma MOTS-c to 305 ± 153% of basal in control (P < 0.01) and to 215 ± 103% of basal in PCOS (P < 0.01) subjects; insulin suppressed intralipid-induced MOTS-c only in controls. Conclusions: In conclusion, this is the first study to show increased lipid enhanced circulating MOTS-c whilst insulin attenuated the MOTS-c response in human. Further, eight weeks of moderate exercise training did not show any changes in circulating MOTS-c levels in healthy controls and in women with PCOS.

Original languageEnglish
JournalClinical Endocrinology
Publication statusPublished - 1 Jan 2019



  • metabolic syndrome
  • mitochondrial dysfunction
  • mitochondrial open reading frame of the 12S rRNA type-c
  • polycystic ovarian syndrome
  • triglycerides and insulin resistance

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Endocrinology

Cite this

Ramanjaneya, M., Jerobin, J., Bettahi, I., Bensila, M., Aye, M., Siveen, K. S., Sathyapalan, T., Skarulis, M., Abou-Samra, A. B., & Atkin, S. (2019). Lipids and insulin regulate mitochondrial-derived peptide (MOTS-c) in PCOS and healthy subjects. Clinical Endocrinology.