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FGF21 responds to PPARalpha & PPARdelta but not PPARgamma, fasting or ketosis in humans
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From: Kofi <k...@anon.un>
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Subject: FGF21 responds to PPARalpha & PPARdelta but not PPARgamma, fasting or ketosis in humans
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J Clin Endocrinol Metab. 2009 Jun 16;
Circulating FGF21 is induced by PPAR agonists but not ketosis in Man.
Christodoulides C, Dyson P, Sprecher D, Tsintzas K, Karpe F.
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.
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 (PPARalpha) activation,
which plays a critical role in regulating metabolism during ketosis.
FGF21 is also a PPARgamma 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 PPARalpha
(20 microg/day GW590735) (n=6), PPARdelta (10 mg/day GW501516) (n=6), or
PPARgamma 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 PPARalpha (39%) and
PPARdelta (32%) but not PPARgamma 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 PPARalpha and PPARdelta and may contribute to the
beneficial metabolic effects observed in response to pharmacotherapy
with these compounds.
PMID: 19531592
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