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

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

Abstract

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.

Citation

Ramanjaneya, M., Jerobin, J., Bettahi, I., Bensila, M., Aye, M., Siveen, K. S., Sathyapalan, T., Skarulis, M., Abou‐Samra, A., & Atkin, S. L. (2019). Lipids and insulin regulate mitochondrial-derived peptide (MOTS-c) in PCOS and healthy subjects. Clinical Endocrinology, 91(2), 278-287. https://doi.org/10.1111/cen.14007

• Journal Article Type: Article
• Acceptance Date: May 1, 2019
• Online Publication Date: May 7, 2019
• Publication Date: Aug 1, 2019
• Deposit Date: May 10, 2019
• Publicly Available Date: May 8, 2020
• Journal: Clinical Endocrinology
• Print ISSN: 0300-0664
• Publisher: Wiley
• Peer Reviewed: Peer Reviewed
• Volume: 91
• Issue: 2
• Pages: 278-287
• DOI: https://doi.org/10.1111/cen.14007
• Keywords: Metabolic syndrome; Mitochondrial dysfunction; Mitochondrial open reading frame of the 12S rRNA type-c; Polycystic ovarian syndrome; Triglycerides and insulin resistance
• Public URL: https://hull-repository.worktribe.com/output/1762091
• Publisher URL: https://onlinelibrary.wiley.com/doi/abs/10.1111/cen.14007
• Contract Date: May 10, 2019