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Dynamic Changes in Circulating Endocrine FGF19 Subfamily and Fetuin-A in Response to Intralipid and Insulin Infusions in Healthy and PCOS Women

Ramanjaneya, Manjunath; Bensila, Milin; Bettahi, Ilham; Jerobin, Jayakumar; Samra, Tareq A.; Aye, Myint Myint; Alkasem, Meis; Siveen, Kodappully Sivaraman; Sathyapalan, Thozhukat; Skarulis, Monica; Atkin, Stephen Lawrence; Abou-Samra, Abdul Badi

Authors

Manjunath Ramanjaneya

Milin Bensila

Ilham Bettahi

Jayakumar Jerobin

Tareq A. Samra

Myint Myint Aye

Meis Alkasem

Kodappully Sivaraman Siveen

Thozhukat Sathyapalan

Monica Skarulis

Stephen Lawrence Atkin

Abdul Badi Abou-Samra



Abstract

© Copyright © 2020 Ramanjaneya, Bensila, Bettahi, Jerobin, Samra, Aye, Alkasem, Siveen, Sathyapalan, Skarulis, Atkin and Abou-Samra. Background: The fibroblast growth factors (FGF) 19 subfamily, also referred to as endocrine FGFs, includes FGF19, FGF21, and FGF23 are metabolic hormones involved in the regulation of glucose and lipid metabolism. Fetuin-A is a hepatokine involved in the regulation of beta-cell function and insulin resistance. Endocrine FGFs and fetuin-A are dysregulated in metabolic disorders including obesity, type 2 diabetes, non-alcoholic fatty liver disease and polycystic ovary syndrome (PCOS). Our study was designed to examine the response of endocrine FGFs and fetuin-A to an acute intralipid, insulin infusion and exercise in PCOS and healthy women. Subjects and Measurements: Ten healthy and 11 PCOS subjects underwent 5-h saline infusions with a hyperinsulinemic-euglycemic clamp (HIEC) performed during the final 2 h. One week later, intralipid infusions were undertaken with a HIEC performed during the final 2 h. After an 8 week of exercise intervention the saline, intralipid, and HIEC were repeated. Plasma levels of endocrine FGFs and fetuin-A were measured. Results: Baseline fetuin-A was higher in PCOS women but FGF19, FGF21, and FGF23 did not differ and were unaffected by exercise. Insulin administration elevated FGF21 in control and PCOS, suppressed FGF19 in controls, and had no effects on FGF23 and fetuin-A. Intralipid infusion suppressed FGF19 and increased FGF21. Insulin with intralipid synergistically increased FGF21 and did not have effects on lipid-mediated suppression of FGF19 in both groups. Conclusion: Our study provides evidence for insulin and lipid regulation of endocrine FGFs in healthy and PCOS women, suggesting that FGF family members play a role in lipid and glucose metabolism. Clinical Trial Registration: www.isrctn.org, Identifier: ISRCTN42448814.

Citation

Ramanjaneya, M., Bensila, M., Bettahi, I., Jerobin, J., Samra, T. A., Aye, M. M., …Abou-Samra, A. B. (2020). Dynamic Changes in Circulating Endocrine FGF19 Subfamily and Fetuin-A in Response to Intralipid and Insulin Infusions in Healthy and PCOS Women. Frontiers in endocrinology, 11, https://doi.org/10.3389/fendo.2020.568500

Journal Article Type Article
Acceptance Date Aug 25, 2020
Publication Date Sep 30, 2020
Deposit Date Oct 29, 2020
Publicly Available Date Nov 2, 2020
Journal Frontiers in Endocrinology
Print ISSN 1664-2392
Electronic ISSN 1664-2392
Publisher Frontiers Media
Peer Reviewed Peer Reviewed
Volume 11
Article Number 568500
DOI https://doi.org/10.3389/fendo.2020.568500
Keywords PCOS (polycystic ovarian syndrome); FGF (fibroblast growth factor); Fetuin A; Hyperinsulimic-euglycemic clamp; FGF19; FGF21
Public URL https://hull-repository.worktribe.com/output/3646956
Publisher URL https://www.frontiersin.org/articles/10.3389/fendo.2020.568500/full

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Copyright Statement
Copyright © 2020 Ramanjaneya, Bensila, Bettahi, Jerobin, Samra, Aye, Alkasem, Siveen, Sathyapalan, Skarulis, Atkin and Abou-Samra. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.





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