FGF21 decreases body weight without reducing food intake or bone mineral density in high-fat fed obese rhesus macaque monkeys.
FGF21 decreases body weight without reducing food intake or bone mineral density in high-fat fed obese rhesus macaque monkeys.
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DOI：
10.1038/s41366-018-0080-7
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发表时间：
2018-06
期刊：
影响因子：
--
通讯作者：
Kievit P
中科院分区：
文献类型：
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作者：
Andersen B;Straarup EM;Heppner KM;Takahashi DL;Raffaele V;Dissen GA;Lewandowski K;Bödvarsdottir TB;Raun K;Grove KL;Kievit P
在肥胖动物模型和短期临床试验中，给予FGF21和FGF21类似物可减轻体重，改善胰岛素敏感性和血脂异常。然而，在小鼠身上发现的潜在不良反应已经引起了人们对FGF21疗法发展的担忧。因此，本研究旨在探讨FGF21对高脂饮食肥胖恒河猴体重、糖脂代谢的影响，以及对骨密度、骨标记物和血浆皮质醇的影响。肥胖的非糖尿病恒河猴(5只雄性和5只去卵巢(OVX)雌性猕猴)被维持在高脂肪饮食下，并用递增剂量的FGF21治疗12周。每天评估食物摄入量，每周评估体重。在研究之前，在治疗期间和冲刷期间多次用DEXA扫描测量骨矿物质含量(BMC)和骨密度。在整个研究过程中同样测量了血糖、糖耐量、胰岛素、血脂、皮质醇和骨标记物。治疗12周后，FGF21的平均体重下降17.6±1.6%。没有观察到对食物摄入量的显著影响。BMC或BMD没有变化，而骨吸收标志物CTX-1增加了2倍。总体而言，糖耐量有所改善，HbA1C略有下降，但幅度很大。此外，FGF21还降低了血浆甘油三酯和极低密度脂蛋白胆固醇的浓度。在研究期间，临床化学标记物没有不良变化，血浆皮质醇也没有变化。总而言之，FGF21在不减少食物摄入量的情况下减轻了肥胖恒河猴的体重。此外，FGF21对身体成分、胰岛素敏感性和血浆甘油三酯也有有益的影响。治疗12周后，骨密度和血浆皮质醇均未见不良反应。
Administration of FGF21 and FGF21 analogues reduce body weight; improve insulin sensitivity and dyslipidemia in animal models of obesity and in short term clinical trials. However potential adverse effects identified in mice have raised concerns for the development of FGF21 therapeutics. Therefore, this study was designed to address the actions of FGF21 on body weight, glucose and lipid metabolism and importantly its effects on bone mineral density (BMD), bone markers, and plasma cortisol in high-fat fed obese rhesus macaque monkeys. Obese non-diabetic rhesus macaque monkeys (five males and five ovariectomized (OVX) females) were maintained on a high-fat diet and treated for 12 weeks with escalating doses of FGF21. Food intake was assessed daily and body weight weekly. Bone mineral content (BMC) and BMD were measured by DEXA scanning prior to the study and on several occasions throughout the treatment period as well as during washout. Plasma glucose, glucose tolerance, insulin, lipids, cortisol, and bone markers were likewise measured throughout the study. On average, FGF21 decreased body weight by 17.6 ± 1.6% after 12 weeks of treatment. No significant effect on food intake was observed. No change in BMC or BMD was observed, while a 2-fold increase in CTX-1, a marker of bone resorption, was seen. Overall glucose tolerance was improved with a small but significant decrease in HbA1C. Furthermore, FGF21 reduced concentrations of plasma triglycerides and very low density lipoprotein cholesterol. No adverse changes in clinical chemistry markers were demonstrated, and no alterations in plasma cortisol were observed during the study. In conclusion, FGF21 reduced body weight in obese rhesus macaque monkeys without reducing food intake. Furthermore, FGF21 had beneficial effects on body composition, insulin sensitivity, and plasma triglycerides. No adverse effects on bone density or plasma cortisol were observed after 12 weeks of treatment.
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影响因子：
82.9
作者：
通讯作者：
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影响因子：
8.1
作者：
Comstock, Sarah M.;Pound, Lynley D.;Grove, Kevin L.
通讯作者：
Grove, Kevin L.
循环的FGF21是肝脏的，并在进食和过度喂养过程中增强了葡萄糖的摄取。
影响因子：
7.7
作者：
Markan KR;Naber MC;Ameka MK;Anderegg MD;Mangelsdorf DJ;Kliewer SA;Mohammadi M;Potthoff MJ
通讯作者：
Potthoff MJ
影响因子：
3.7
作者：
Muise ES;Souza S;Chi A;Tan Y;Zhao X;Liu F;Dallas-Yang Q;Wu M;Sarr T;Zhu L;Guo H;Li Z;Li W;Hu W;Jiang G;Paweletz CP;Hendrickson RC;Thompson JR;Mu J;Berger JP;Mehmet H
通讯作者：
Mehmet H
影响因子：
82.9
作者：
通讯作者：
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