Circulating Fibroblast Growth Factor 21 Is Induced by Peroxisome Proliferator-Activated Receptor Agonists But Not Ketosis in Man
Circulating Fibroblast Growth Factor 21 Is Induced by Peroxisome Proliferator-Activated Receptor Agonists But Not Ketosis in Man
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DOI：
10.1210/jc.2009-0111
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发表时间：
2009-09-01
影响因子：
5.8
通讯作者：
Karpe, Fredrik
中科院分区：
文献类型：
--
作者：
Christodoulides, Constantinos;Dyson, Pamela;Karpe, Fredrik
内容：鼠成纤维细胞生长因子（FGF）21是一种由肝脏分泌的营养调节激素，主要响应过氧化物酶体增殖物激活受体-α（PPAR α）激活，在酮症期间调节代谢中起关键作用。FGF 21也是小鼠脂肪组织中的PPAR γ靶基因。本研究的目的是在禁食、生酮饮食和过氧化物酶体增殖物激活物受体激动剂治疗期间测定血浆FGF 21水平。设计和设置：我们进行了一项前瞻性研究，涉及两所大学医院的三组患者。7名肥胖者被分配到低碳水化合物饮食3个月（组2）;三组健康、超重或肥胖的男性志愿者接受了PPAR α治疗，（20 μ g/d GW590735）（n = 6），PPAR δ（10 mg/d GW 501516）（n = 6）或PPAR γ激动剂结果：空腹和再进食期间血浆FGF 21水平无明显变化，空腹和再进食期间血浆FGF 21水平无明显变化，空腹和再进食期间血浆FGF 21水平无明显变化。3个月生酮饮食与血浆FGF 21水平下降42%相关。循环中的FGF 21在接受PPAR α（39%）和PPAR δ（32%）治疗后显著增加，而在接受PPAR γ激动剂治疗后则没有显著增加。FGF 21在调节人的禁食反应或酮症中不起主要作用。血浆FGF 21响应于PPAR α和PPAR δ的药理学活化而升高，并且可能有助于在以下中观察到的有益代谢作用：对这些化合物的药物治疗的反应。（临床内分泌代谢杂志94：3594-3601，2009）
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: 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 alpha (20 mu g/d GW590735) (n = 6), PPAR delta (10 mg/d GW501516) (n = 6), or PPAR gamma 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 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. (J Clin Endocrinol Metab 94: 3594-3601, 2009)