This Article Full Text Full Text (PDF) Supplemental Data Submit a related Letter to the Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Google Scholar Articles by Christodoulides, C. Articles by Karpe, F. PubMed PubMed Citation Articles by Christodoulides, C. Articles by Karpe, F. Related Collections Metabolism

Circulating Fibroblast Growth Factor 21 Is Induced by Peroxisome Proliferator-Activated Receptor Agonists But Not Ketosis in Man

Oxford Centre for Diabetes, Endocrinology, and Metabolism (C.C., P.D., F.K.), Churchill Hospital, Oxford OX3 7LJ, United Kingdom; National Institute for Health Research, Oxford Biomedical Research Centre (C.C., F.K.), Oxford Radcliffe Hospitals Trust, Churchill Hospital, Oxford OX3 7LJ, United Kingdom; Cardiovascular and Urogenital Centre for Excellence in Drug Discovery (D.S.), GlaxoSmithKline, King of Prussia, Pennsylvania 19406; and Centre for Integrated Systems Biology and Medicine (K.T.), School of Biomedical Sciences, Nottingham University, Nottingham NG7 2UH, United Kingdom

Address all correspondence and requests for reprints to: Dr. F. Karpe, OCDEM, Churchill Hospital, Oxford OX3 7LJ, United Kingdom. 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- (PPAR) activation, which plays a critical role in regulating metabolism during ketosis. FGF21 is also a PPAR target gene in mouse adipose tissue. Little information is available on FGF21 functions in humans.

Objective: The aim of the study was to measure plasma FGF21 during fasting, ketogenic diet, and PPAR agonist treatment in humans.

Design and Setting: We conducted a prospective study involving three patient groups at two university hospitals.

Patients: Eight healthy male volunteers underwent a 48-h period of starvation followed by 24-h refeeding (group 1); seven obese individuals were allocated to a low-carbohydrate diet for 3 months (group 2); and three groups of healthy, overweight or obese male volunteers received treatment with a PPAR (20 µg/d GW590735) (n=6), PPAR (10 mg/d GW501516) (n=6), or PPAR agonist (rosiglitazone) (n=10) for 2 wk (group 3).

Main Outcome Measures: Fasting plasma FGF21 and serum 3-hydroxybutyrate were measured.

Results: There was no significant variation in human plasma FGF21 during fasting and refeeding. A 3-month ketogenic diet was associated with a 42% decline in plasma FGF21 levels. Circulating FGF21 increased significantly in response to treatment with PPAR (39%) and PPAR (32%), but not PPAR 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 and PPAR and may contribute to the beneficial metabolic effects observed in response to pharmacotherapy with these compounds.