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

Research output: Contribution to journalArticle

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.

Original languageEnglish
JournalClinical Endocrinology
DOIs
Publication statusPublished - 1 Jan 2019

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Polycystic Ovary Syndrome
Healthy Volunteers
Insulin
Lipids
Peptides
Exercise
Insulin Resistance
AMP-Activated Protein Kinases
Glucose Clamp Technique
phospholipid emulsion soybean oil
Enzyme-Linked Immunosorbent Assay

Keywords

  • 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

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.

In: Clinical Endocrinology, 01.01.2019.

Research output: Contribution to journalArticle

Ramanjaneya, M, Jerobin, J, Bettahi, I, Bensila, M, Aye, M, Siveen, KS, Sathyapalan, T, Skarulis, M, Abou-Samra, AB & Atkin, S 2019, 'Lipids and insulin regulate mitochondrial-derived peptide (MOTS-c) in PCOS and healthy subjects', Clinical Endocrinology. https://doi.org/10.1111/cen.14007
Ramanjaneya, Manjunath ; Jerobin, Jayakumar ; Bettahi, Ilham ; Bensila, Milin ; Aye, Myint ; Siveen, Kodappully Sivaraman ; Sathyapalan, Thozhukat ; Skarulis, Monica ; Abou-Samra, Abdul Badi ; Atkin, Stephen. / Lipids and insulin regulate mitochondrial-derived peptide (MOTS-c) in PCOS and healthy subjects. In: Clinical Endocrinology. 2019.
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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.",
keywords = "metabolic syndrome, mitochondrial dysfunction, mitochondrial open reading frame of the 12S rRNA type-c, polycystic ovarian syndrome, triglycerides and insulin resistance",
author = "Manjunath Ramanjaneya and Jayakumar Jerobin and Ilham Bettahi and Milin Bensila and Myint Aye and Siveen, {Kodappully Sivaraman} and Thozhukat Sathyapalan and Monica Skarulis and Abou-Samra, {Abdul Badi} and Stephen Atkin",
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AU - Ramanjaneya, Manjunath

AU - Jerobin, Jayakumar

AU - Bettahi, Ilham

AU - Bensila, Milin

AU - Aye, Myint

AU - Siveen, Kodappully Sivaraman

AU - Sathyapalan, Thozhukat

AU - Skarulis, Monica

AU - Abou-Samra, Abdul Badi

AU - Atkin, Stephen

PY - 2019/1/1

Y1 - 2019/1/1

N2 - 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.

AB - 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.

KW - metabolic syndrome

KW - mitochondrial dysfunction

KW - mitochondrial open reading frame of the 12S rRNA type-c

KW - polycystic ovarian syndrome

KW - triglycerides and insulin resistance

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