Fibroblast activation protein is a GH target: A prospective study of patients with acromegaly before and after treatment

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Fibroblast activation protein is a GH target: A prospective study of patients with acromegaly before and after treatment. / Arlien-Søborg, Mai C; Grøndahl, Camilla; Bæk, Amanda; Dal, Jakob; Alle Madsen, Michael; Høgild, Morten Lyng; Pedersen, Steen B; Bjerre, Mette; Jørgensen, Jens O L.

I: Journal of Clinical Endocrinology and Metabolism, 23.09.2019.

Publikation: Bidrag til tidsskrift/Konferencebidrag i tidsskrift /Bidrag til avisTidsskriftartikelForskningpeer review

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@article{0b1e2b5f26704e6c991873a7eaef3989,
title = "Fibroblast activation protein is a GH target: A prospective study of patients with acromegaly before and after treatment",
abstract = "BACKGROUND: Fibroblast growth factor 21 (FGF21) is a circulating hormone with pleiotropic metabolic effects, which is inactivated by fibroblast activation protein (FAP). Data regarding interaction between FGF21, FAP and growth hormone (GH) are limited, but it is noteworthy that collagens are also FAP substrates since GH potently stimulates collagen turnover.AIM: To measure circulating FGF21 components including FAP in patients with acromegaly before and after disease control.METHODS: Eighteen patients with active acromegaly were studied at time of diagnosis and ≥ 6 months after disease control by either surgery or medical treatment. Serum levels of total and active FGF21, β-klotho, FAP and collagen turnover markers were measured by immunoassays. Expression of putative FGF21-dependent genes were measured in adipose tissue by RT-PCR, body composition assessed by DXA scan, and insulin sensitivity estimated with HOMA-IR.RESULTS: Total FGF21, active FGF21 and β-klotho remained unchanged. Insulin sensitivity and body fat mass increased after disease control but neither correlated with active FGF21. Expression of FGF21-dependent genes did not change after treatment. FAP levels (µg/l) were markedly reduced after treatment [105.6 ± 29.4 vs. 62.2 ± 32.4, p<0.000]. Collagen turnover markers also declined significantly after treatment and ΔFAP correlated positively with ΔProcollagen Type I (p<0.000) and Type III (p<0.000).CONCLUSION: 1)Circulating FGF21 and β-klotho do not change in response to acromegaly treatment, 2) FAP concentrations in serum decrease after disease control and correlate positively with collagen turnover markers, 3)FAP is a hitherto unrecognized GH target linked to collagen turnover.",
author = "Arlien-S{\o}borg, {Mai C} and Camilla Gr{\o}ndahl and Amanda B{\ae}k and Jakob Dal and {Alle Madsen}, Michael and H{\o}gild, {Morten Lyng} and Pedersen, {Steen B} and Mette Bjerre and J{\o}rgensen, {Jens O L}",
note = "{\circledC} Endocrine Society 2019. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.",
year = "2019",
month = "9",
day = "23",
doi = "10.1210/clinem/dgz033",
language = "English",
journal = "Journal of Clinical Endocrinology and Metabolism",
issn = "0021-972X",
publisher = "Oxford University Press",

}

RIS

TY - JOUR

T1 - Fibroblast activation protein is a GH target: A prospective study of patients with acromegaly before and after treatment

AU - Arlien-Søborg, Mai C

AU - Grøndahl, Camilla

AU - Bæk, Amanda

AU - Dal, Jakob

AU - Alle Madsen, Michael

AU - Høgild, Morten Lyng

AU - Pedersen, Steen B

AU - Bjerre, Mette

AU - Jørgensen, Jens O L

N1 - © Endocrine Society 2019. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

PY - 2019/9/23

Y1 - 2019/9/23

N2 - BACKGROUND: Fibroblast growth factor 21 (FGF21) is a circulating hormone with pleiotropic metabolic effects, which is inactivated by fibroblast activation protein (FAP). Data regarding interaction between FGF21, FAP and growth hormone (GH) are limited, but it is noteworthy that collagens are also FAP substrates since GH potently stimulates collagen turnover.AIM: To measure circulating FGF21 components including FAP in patients with acromegaly before and after disease control.METHODS: Eighteen patients with active acromegaly were studied at time of diagnosis and ≥ 6 months after disease control by either surgery or medical treatment. Serum levels of total and active FGF21, β-klotho, FAP and collagen turnover markers were measured by immunoassays. Expression of putative FGF21-dependent genes were measured in adipose tissue by RT-PCR, body composition assessed by DXA scan, and insulin sensitivity estimated with HOMA-IR.RESULTS: Total FGF21, active FGF21 and β-klotho remained unchanged. Insulin sensitivity and body fat mass increased after disease control but neither correlated with active FGF21. Expression of FGF21-dependent genes did not change after treatment. FAP levels (µg/l) were markedly reduced after treatment [105.6 ± 29.4 vs. 62.2 ± 32.4, p<0.000]. Collagen turnover markers also declined significantly after treatment and ΔFAP correlated positively with ΔProcollagen Type I (p<0.000) and Type III (p<0.000).CONCLUSION: 1)Circulating FGF21 and β-klotho do not change in response to acromegaly treatment, 2) FAP concentrations in serum decrease after disease control and correlate positively with collagen turnover markers, 3)FAP is a hitherto unrecognized GH target linked to collagen turnover.

AB - BACKGROUND: Fibroblast growth factor 21 (FGF21) is a circulating hormone with pleiotropic metabolic effects, which is inactivated by fibroblast activation protein (FAP). Data regarding interaction between FGF21, FAP and growth hormone (GH) are limited, but it is noteworthy that collagens are also FAP substrates since GH potently stimulates collagen turnover.AIM: To measure circulating FGF21 components including FAP in patients with acromegaly before and after disease control.METHODS: Eighteen patients with active acromegaly were studied at time of diagnosis and ≥ 6 months after disease control by either surgery or medical treatment. Serum levels of total and active FGF21, β-klotho, FAP and collagen turnover markers were measured by immunoassays. Expression of putative FGF21-dependent genes were measured in adipose tissue by RT-PCR, body composition assessed by DXA scan, and insulin sensitivity estimated with HOMA-IR.RESULTS: Total FGF21, active FGF21 and β-klotho remained unchanged. Insulin sensitivity and body fat mass increased after disease control but neither correlated with active FGF21. Expression of FGF21-dependent genes did not change after treatment. FAP levels (µg/l) were markedly reduced after treatment [105.6 ± 29.4 vs. 62.2 ± 32.4, p<0.000]. Collagen turnover markers also declined significantly after treatment and ΔFAP correlated positively with ΔProcollagen Type I (p<0.000) and Type III (p<0.000).CONCLUSION: 1)Circulating FGF21 and β-klotho do not change in response to acromegaly treatment, 2) FAP concentrations in serum decrease after disease control and correlate positively with collagen turnover markers, 3)FAP is a hitherto unrecognized GH target linked to collagen turnover.

U2 - 10.1210/clinem/dgz033

DO - 10.1210/clinem/dgz033

M3 - Journal article

JO - Journal of Clinical Endocrinology and Metabolism

JF - Journal of Clinical Endocrinology and Metabolism

SN - 0021-972X

ER -