Lauritzen Esben Stistrup, Svart Mads Vandsted, Voss Thomas, Møller Niels, Bjerre Mette
Medical Research Laboratory, Aarhus University , Aarhus N, Denmark.
Steno Diabetes Center Aarhus, Aarhus University Hospital , Aarhus N, Denmark.
Endocr Res. 2021 Feb;46(1):20-27. doi: 10.1080/07435800.2020.1831015. Epub 2020 Oct 19.
Fibroblast growth factor (FGF) 21 is a circulating hormone with metabolic regulatory importance. In mice, FGF21 increases in response to a ketogenic diet and fasting. In humans, a similar increase is only observed after prolonged starvation. We aim to study the acute effects of ketone bodies on circulating FGF21 levels in humans.
Participants from three randomized, placebo-controlled crossover studies, with increased endogenous or exogenous ketone bodies, were included. Study 1: patients with type 1 diabetes (T1D) (n = 9) were investigated after a) insulin deprivation and lipopolysaccharide (LPS) injection and b) insulin-controlled euglycemia. Study 2: patients with T1D (n = 9) were investigated after a) total insulin deprivation for 9 hours and b) insulin-controlled euglycemia. Study 3: Healthy adults (n = 9) were examined during a) 3-hydroxybutyrate (OHB) infusion and b) saline infusion. Plasma FGF21 was measured with immunoassay in serial samples.
Circulating OHB levels were significantly increased to 1.3, 1.5, and 5.5 mmol/l in the three studies, but no correlations with FGF21 levels were found. Also, no correlations between FGF21, insulin, or glucagon were found. Insulin deprivation and LPS injection resulted in increased plasma FGF21 levels at t = 120 min ( = .005) which normalized at t = 240 min.
We found no correlation between circulating FGF21 levels and levels of ketone bodies. This suggests that it is not ketosis which controls FGF21 production, but instead a rather more complex regulatory mechanism.
clinicaltrials.gov ID number: Study 1: NCT02157155 (5/6-2014), study 2: NCT02077348 (4/3-2014), and study 3: NCT02357550 (6/2-2015).
成纤维细胞生长因子（FGF）21是一种具有代谢调节重要性的循环激素。在小鼠中，FGF21会因生酮饮食和禁食而增加。在人类中，只有在长期饥饿后才会观察到类似的增加。我们旨在研究酮体对人体循环FGF21水平的急性影响。
纳入了三项随机、安慰剂对照交叉研究的参与者，这些研究中内源性或外源性酮体增加。研究1：1型糖尿病（T1D）患者（n = 9）在a）胰岛素剥夺和注射脂多糖（LPS）后以及b）胰岛素控制的正常血糖状态下接受调查。研究2：T1D患者（n = 9）在a）完全胰岛素剥夺9小时后以及b）胰岛素控制的正常血糖状态下接受调查。研究3：健康成年人（n = 9）在a）输注3-羟基丁酸（OHB）期间以及b）输注生理盐水期间接受检查。用免疫分析法在系列样本中测量血浆FGF21。
在三项研究中，循环OHB水平显著升高至1.3、1.5和5.5 mmol/l，但未发现与FGF21水平相关。此外，未发现FGF21、胰岛素或胰高血糖素之间存在相关性。胰岛素剥夺和注射LPS导致在t = 120分钟时血浆FGF21水平升高（P = 0.005），在t = 240分钟时恢复正常。
我们发现循环FGF21水平与酮体水平之间无相关性。这表明控制FGF21产生的不是酮症，而是一种更为复杂的调节机制。
clinicaltrials.gov识别号：研究1：NCT02157155（2014年5月6日）；研究2：NCT02077348（2014年4月3日）；研究3：NCT02357550（2015年6月2日）。
