help button home button Endocrine Society JCEM
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH
This version published online on June 16, 2009
Journal of Clinical Endocrinology & Metabolism , doi:10.1210/jc.2009-0111
This Article
Right arrow Author Manuscript (PDF)
Right arrow Supplemental Data
Right arrow All Versions of this Article:
94/9/3594    most recent
Author Manuscript (PDF)
Right arrow Submit a related Letter to the Editor
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow Reprints, Permissions and Rights
Citing Articles
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Christodoulides, C.
Right arrow Articles by Karpe, F.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Christodoulides, C.
Right arrow Articles by Karpe, F.
Related Collections
Right arrow Metabolism

Submitted on January 21, 2009
Accepted on June 8, 2009

Circulating FGF21 is induced by PPAR agonists but not ketosis in Man

Constantinos Christodoulides, Pamela Dyson, Dennis Sprecher, Kostas Tsintzas, and Fredrik Karpe*

Oxford Centre for Diabetes, Endocrinology and Metabolism, Churchill Hospital, Oxford, UK; NIHR Oxford Biomedical Research Centre, ORH Trust, Churchill Hospital, Oxford, UK; Cardiovascular and Urogenital Centre for Excellence in Drug Discovery, GlaxoSmithKline, King of Prussia, Pennsylvania; Centre for Integrated Systems Biology and Medicine, School of Biomedical Sciences, Nottingham University, Nottingham, NG7 2UH, United Kingdom

* To whom correspondence should be addressed. E-mail: fredrik.karpe{at}ocdem.ox.ac.uk.

CONTEXT: Murine fibroblast growth factor (FGF) 21 is a nutritionally regulated hormone secreted by the liver principally in response to peroxisome proliferator-activated receptor-{alpha} (PPAR{alpha}) activation, which plays a critical role in regulating metabolism during ketosis. FGF21 is also a PPAR{gamma} target gene in mouse adipose tissue. Little information is available on FGF21 functions in humans.

OBJECTIVE: To measure plasma FGF21 during fasting, ketogenic diet, and PPAR agonist treatment in humans.

DESIGN: Prospective study involving 3 patient groups.

SETTING: Two university hospitals.

PATIENTS: Eight healthy male volunteers undergoing a 48-hour period of starvation followed by 24-hours re-feeding (group 1); Seven obese individuals allocated to a low-carbohydrate diet for 3 months (group 2); Three groups of healthy, overweight or obese male volunteers receiving treatment with a PPAR{alpha} (20 µg/day GW590735) (n=6), PPAR{delta} (10 mg/day GW501516) (n=6), or PPAR{gamma} agonist (rosiglitazone) (n=10) for 2 weeks (group 3).

MAIN OUTCOME MEASURES: Fasting plasma FGF21 and serum 3-hydroxybutyrate.

RESULTS: There was no significant variation in human plasma FGF21 during fasting and re-feeding. A three month ketogenic diet was associated with a 42% decline in plasma FGF21 levels. Circulating FGF21 increased significantly in response to treatment with PPAR{alpha} (39%) and PPAR{delta} (32%) but not PPAR{gamma} agonists.

CONCLUSION: FGF21 does not play a major role in regulating the fasting response or ketosis in man. However, plasma FGF21 is elevated in response to pharmacological activation of PPAR{alpha} and PPAR{delta} and may contribute to the beneficial metabolic effects observed in response to pharmacotherapy with these compounds.
Key words: FGF21 • ketosis • PPAR • human






HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH
Endocrinology Endocrine Reviews J. Clin. End. & Metab.
Molecular Endocrinology Recent Prog. Horm. Res. All Endocrine Journals
Copyright © 2009 by The Endocrine Society