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首页> 外文期刊>Growth hormone and IGF research: Official journal of the Growth Hormone Research Society and the International IGF Research Society >Fibroblast growth factor 21 decreases after liver fat reduction via growth hormone augmentation
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Fibroblast growth factor 21 decreases after liver fat reduction via growth hormone augmentation

机译：通过生长激素增强肝脂肪减少后成纤维细胞生长因子21降低

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Abstract Objective Fibroblast growth factor 21 (FGF21) ameliorates steatohepatitis but is increased in humans with fatty liver, potentially due to compensatory mechanisms and/or FGF21 resistance. Further, animal models suggest that GH increases serum FGF21. Tesamorelin, a growth hormone releasing hormone agonist, reduces liver fat in HIV-infected individuals. The objectives of this study were to investigate changes in FGF21 during tesamorelin treatment, to elucide the interplay between FGF21, GH augmentation, and liver fat reduction in humans. Methods 50 HIV-infected men and women with increased abdominal adiposity participated in this randomized, placebo-controlled trial of tesamorelin, 2mg vs. identical placebo daily for six months. Fasting laboratory measures, liver fat by 1 H-magnetic resonance spectroscopy, and visceral adipose tissue (VAT) by computed tomography were obtained. Euglycemic hyperinsulinemic clamp was performed in a randomly selected subset. Results At baseline, serum log 10 FGF21 was significantly associated with log 10 liver fat ( r =0.32, p =0.03). Log 10 FGF21 tended to decrease in the tesamorelin group compared to placebo ( p =0.06). Among the entire cohort, reductions in FGF21 were significantly associated with reductions in liver fat (ρ=0.41, p =0.01), log 10 gamma glutamyl tran speptidase (GGT, r =0.40, p =0.009), and FIB4 index ( r =0.37, p =0.02). Conclusions In HIV-infected individuals, FGF21 is significantly positively associated with liver fat. FGF21 decreases in association with reductions in liver fat, GGT, and FIB4, suggesting that FGF21 is upregulated in the context of steatosis and steatohepatitis and is reduced when these conditions improve. Moreover, these data suggest that tesamorelin improves liver fat via pathways other than increasing serum FGF21. Trial registration clinicaltrials.gov NCT01263717 . Highlights ? FGF21 is positively associated with liver fat content in HIV-infected individuals ? Reductions in liver fat achieved with tesamorelin are significantly associated with reductions in FGF21, GGT, and FIB4. ? These data suggest that FGF21 is upregulated with increased liver fat, and tesamorelin's effect is not mediated via FGF21.
机译：摘要目的成纤维细胞生长因子21（FGF21）改善脂肪性肝炎，但在具有脂肪肝的人体中增加，可能是由于补偿机制和/或FGF21抗性。此外，动物模型表明GH增加血清FGF21。 Tesamorelin是一种释放激素激动剂的生长激素，减少了艾滋病毒感染的个体中的肝脏脂肪。本研究的目的是探讨Tesamorelin治疗期间FGF21的变化，均含有FGF21，GH增强和人类肝脏脂肪减少之间的相互作用。方法50例艾滋病毒感染的男性和腹部肥胖的男性和妇女参与了Tesamorelin的这种随机，安慰剂对照试验，每天六个月持续6个月。获得禁食实验室措施，肝脏脂肪通过1 H磁共振光谱和通过计算断层扫描的内脏脂肪组织（VAT）。在随机选择的子集中进行神经血糖高胰岛素纤维素纤维素。基线的结果，血清Log 10 FGF21与Log 10肝脏脂肪显着相关（r = 0.32，p = 0.03）。与安慰剂相比，Log 10 FGF21倾向于降低Tesamorelin组（P = 0.06）。在整个队列中，FGF21的减少与肝脏脂肪的减少显着相关（ρ= 0.41，p = 0.01），Log 10γ谷氨酸Tran纯酶（GGT，r = 0.40，p = 0.009）和FIB4指数（R = 0.37，p = 0.02）。结论在艾滋病毒感染的个体中，FGF21与肝脏脂肪显着呈正相关。 FGF21与肝脏脂肪，GGT和FIB4的减少结合减少，表明FGF21在脂肪变性和胫骨肝炎的背景下上调，并且在这些条件改善时减少。此外，这些数据表明Tesamorelin通过除血清FGF21之外的途径改善肝脏脂肪。试验登记ClinicalTrials.gov NCT01263717。强调 ？ FGF21与艾滋病毒感染的个体中的肝脂肪含量正相关？用Tesamorelin实现的肝脏脂肪减少与FGF21，GGT和FIB4的减少显着相关。还这些数据表明FGF21随着肝脏脂肪增加而上调，并且Tesamorelin的效果未通过FGF21介导。

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