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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


Manjunath Ramanjaneya

Jayakumar Jerobin

Ilham Bettahi

Milin Bensila

Myint Aye

Kodappully Sivaraman Siveen

Monica Skarulis

Abdul?Badi Abou?Samra

Stephen Lawrence Atkin


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.
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.


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.

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
Keywords Metabolic syndrome; Mitochondrial dysfunction; Mitochondrial open reading frame of the 12S rRNA type-c; Polycystic ovarian syndrome; Triglycerides and insulin resistance
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