FGF21型
能量稳态
旁分泌信号
生物
脂肪组织
葡萄糖稳态
2型糖尿病
成纤维细胞生长因子
生物信息学
肥胖
内分泌系统
糖尿病
内科学
激素
内分泌学
医学
胰岛素抵抗
受体
生物化学
作者
Jo Lewis,F. J. Ebling,Ricardo J. Samms,Kostas Tsintzas
标识
DOI:10.1016/j.tem.2019.05.007
摘要
FGF21 is an endocrine factor shown to impact whole-body metabolism in preclinical species and adult humans. FGF21 is under investigation as a novel therapeutic agent for the treatment of diabetes and its associated comorbidities. Expression of the FGF21 receptor/β-klotho complex (FGFR1-KLB) determines target tissue specificity; adipose tissue, liver, and the central nervous system have emerged as key target organs. Engineered FGF21 analogs, at pharmacological levels, show considerable improvement in the metabolic syndrome phenotype in animal models. However, only some of these effects (reduced dyslipidemia and body weight) are evident in humans. This represents a significant challenge for the translational potential of engineered FGF21-based therapeutics. Fibroblast growth factor 21 (FGF21) is a protein highly synthesized in the liver that exerts paracrine and endocrine control of many aspects of energy homeostasis in multiple tissues. In preclinical models of obesity and type 2 diabetes, treatment with FGF21 improves glucose homeostasis and promotes weight loss, and, as a result, FGF21 has attracted considerable attention as a therapeutic agent for the treatment of metabolic syndrome in humans. An improved understanding of the biological role of FGF21 may help to explain why its therapeutic potential in humans has not been fully realized. This review will cover the complexities in FGF21 biology in rodents and humans, with emphasis on its role in protection from central and peripheral facets of obesity. Fibroblast growth factor 21 (FGF21) is a protein highly synthesized in the liver that exerts paracrine and endocrine control of many aspects of energy homeostasis in multiple tissues. In preclinical models of obesity and type 2 diabetes, treatment with FGF21 improves glucose homeostasis and promotes weight loss, and, as a result, FGF21 has attracted considerable attention as a therapeutic agent for the treatment of metabolic syndrome in humans. An improved understanding of the biological role of FGF21 may help to explain why its therapeutic potential in humans has not been fully realized. This review will cover the complexities in FGF21 biology in rodents and humans, with emphasis on its role in protection from central and peripheral facets of obesity.
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