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首页> 外文期刊>Molecular Metabolism >The FGF21 response to fructose predicts metabolic health and persists after bariatric surgery in obese humans
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The FGF21 response to fructose predicts metabolic health and persists after bariatric surgery in obese humans

机译：FGF21对果糖的反应可预测肥胖者减肥手术后的代谢健康并持续存在

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Objective: Fructose consumption has been implicated in the development of obesity and insulin resistance. Emerging evidence shows that fibroblast growth factor 21 (FGF21) has beneficial effects on glucose, lipid, and energy metabolism and may also mediate an adaptive response to fructose ingestion. Fructose acutely stimulates circulating FGF21 consistent with a hormonal response. We aimed to evaluate whether fructose-induced FGF21 secretion is linked to metabolic outcomes in obese humans before and after bariatric surgery-induced weight loss. Methods: We recruited 40 Roux-en-Y gastric bypass patients and assessed the serum FGF21 response to fructose (75-g fructose tolerance test) and basal and insulin-mediated glucose and lipid fluxes during a 2-step hyperinsulinemic-euglycemic clamp with infusion of [6,6-^2H"2] glucose and [1,1,2,3,3-^2H"5] glycerol. Liver biopsies were obtained during bariatric surgery. Nineteen subjects underwent the same assessments at 1-year follow-up. Results: Serum FGF21 increased 3-fold at 120 min after fructose ingestion and returned to basal levels at 300 min. Neither basal FGF21 nor the fructose-FGF21 response correlated with liver fat content or liver histopathology, but increased levels were associated with elevated endogenous glucose production, increased lipolysis, and peripheral/muscle insulin resistance. At 1-year follow-up, subjects had lost 28 +/- 6% of body weight and improved in all metabolic outcomes, but fructose-stimulated FGF21 dynamics did not markedly differ from the pre-surgical state. The association between increased basal and stimulated FGF21 levels with poor metabolic health was no longer present after weight loss. Conclusions: Fructose ingestion in obese humans stimulates FGF21 secretion, and this response is related to systemic metabolism. Further studies are needed to establish if FGF21 signaling is (patho)physiologically involved in fructose metabolism and metabolic health.
机译：目的：果糖的摄入与肥胖和胰岛素抵抗的发展有关。新兴证据表明，成纤维细胞生长因子21（FGF21）对葡萄糖，脂质和能量代谢具有有益作用，并且还可能介导对果糖摄入的适应性反应。果糖可急性刺激循环的FGF21，与激素反应一致。我们旨在评估减肥手术诱导的减肥前后果糖诱导的FGF21分泌是否与肥胖人群的代谢结果相关。方法：我们招募了40名Roux-en-Y胃搭桥术患者，并在输注2步高胰岛素-正常血糖钳夹期间评估了血清FGF21对果糖的反应（75 g果糖耐受性测试）以及基础和胰岛素介导的葡萄糖和脂质通量[6,6- ^ 2H“ 2]葡萄糖和[1,1,2,3,3- ^ 2H” 5]甘油。减肥手术期间获得了肝活检。在1年的随访中，对19名受试者进行了相同的评估。结果：果糖摄入后120分钟，血清FGF21升高了3倍，而300分钟后又恢复了基础水平。基础FGF21或果糖FGF21响应均与肝脂肪含量或肝组织病理学均不相关，但水平升高与内源性葡萄糖生成增加，脂解增加以及外周/肌肉胰岛素抵抗相关。在1年的随访中，受试者的体重减轻了28 +/- 6％，并且所有代谢结果均得到改善，但是果糖刺激的FGF21动力学与手术前状态没有显着差异。体重减轻后，不再存在基础和刺激的FGF21水平升高与新陈代谢健康之间的关联。结论：肥胖的人摄入果糖会刺激FGF21的分泌，而这种反应与全身代谢有关。需要进一步的研究来确定FGF21信号传导是否在果糖代谢和代谢健康方面（病理）生理参与。

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