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Regulation of circulating CTRP-2/CTRP-9 and GDF-8/GDF-15 by intralipids and insulin in healthy control and polycystic ovary syndrome women following chronic exercise training

Jerobin, Jayakumar; Ramanjaneya, Manjunath; Bettahi, Ilham; Parammal, Raihanath; Siveen, Kodappully Sivaraman; Alkasem, Meis; Aye, Myint; Sathyapalan, Thozhukat; Skarulis, Monica; Atkin, Stephen L.; Abou-Samra, Abdul Badi


Jayakumar Jerobin

Manjunath Ramanjaneya

Ilham Bettahi

Raihanath Parammal

Kodappully Sivaraman Siveen

Meis Alkasem

Myint Aye

Thozhukat Sathyapalan

Monica Skarulis

Stephen L. Atkin

Abdul Badi Abou-Samra


Background: Polycystic ovary syndrome (PCOS) is associated with obesity, diabetes, and insulin resistance. The circulating C1Q/TNF-related proteins (CTRP-2, CTRP-9) and growth differentiation factors (GDF-8, GDF-15) contribute to glucose and lipid homeostasis. The effects of intralipids and insulin infusion on CTRP-2, CTRP-9, GDF-8 and GDF-15 in PCOS and control subjects before and after chronic exercise training were examined. Methods: Ten PCOS and nine healthy subjects were studied at baseline status and after moderate-intensity chronic exercise training (1 h exercise, 3 times per week, 8 weeks). All participants were infused with 1.5 mL/min of saline or intralipids (20%) for 5 h, and during the last 2 h of saline or intralipids infusion hyperinsulinemic-euglycemic clamp (HIEC) was performed. CTRP-2, CTRP-9, GDF-8 and GDF-15 levels were measured at 0, 3 and 5 h. Results: Intralipids dramatically increased CTRP-2 levels in PCOS (P = 0.02) and control (P = 0.004) subjects, which was not affected by insulin infusion or by exercise. Intralipids alone had no effects on CTRP-9, GDF-8, or GDF-15. Insulin increased the levels of GDF-15 in control subjects (P = 0.05) during the saline study and in PCOS subjects (P = 0.04) during the intralipid infusion. Insulin suppressed CTRP9 levels during the intralipid study in both PCOS (P = 0.04) and control (P = 0.01) subjects. Exercise significantly reduced fasting GDF-8 levels in PCOS (P = 0.03) and control (P = 0.04) subjects; however, intralipids infusion after chronic exercise training increased GDF-8 levels in both PCOS (P = 0.003) and control (P = 0.05) subjects and insulin infusion during intralipid infusion reduced the rise of GDF-8 levels. Conclusion: This study showed that exogenous lipids modulate CTRP-2, which might have a physiological role in lipid metabolism. Since chronic exercise training reduced fasting GDF-8 levels; GDF-8 might have a role in humoral adaptation to exercise. GDF-15 and CTRP-9 levels are responsive to insulin, and thus they may play a role in insulin responses.


Jerobin, J., Ramanjaneya, M., Bettahi, I., Parammal, R., Siveen, K. S., Alkasem, M., …Abou-Samra, A. B. (2021). Regulation of circulating CTRP-2/CTRP-9 and GDF-8/GDF-15 by intralipids and insulin in healthy control and polycystic ovary syndrome women following chronic exercise training. Lipids in Health and Disease, 20(1), Article 34.

Journal Article Type Article
Acceptance Date Apr 6, 2021
Online Publication Date Apr 19, 2021
Publication Date Dec 1, 2021
Deposit Date May 15, 2021
Publicly Available Date May 18, 2021
Journal Lipids in Health and Disease
Print ISSN 1476-511X
Electronic ISSN 1476-511X
Publisher Springer Verlag
Peer Reviewed Peer Reviewed
Volume 20
Issue 1
Article Number 34
Keywords C1Q/TNF related proteins; Growth differentiation factors; Lipid; Insulin; Insulin resistance; Euglycemic clamp; Exercise and polycystic ovary syndrome
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© The Author(s). 2021. Open Access. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit Creative Commons Public Domain Dedication waiver ( applies to the data made available in this article, unless otherwise stated in a credit line to the data.

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