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., …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
• Electronic ISSN: 1365-2265
• 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