Fibroblast growth factor 21: update on genetics and molecular biology.

IF 3.8 3区 医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY
Daniel R Barros, Robert A Hegele
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引用次数: 0

Abstract

Purpose of review: Since its discovery, most research on fibroblast growth factor 21 (FGF21) has focused on its antihyperglycemia properties. However, attention has recently shifted towards elucidating the ability of FGF21 to lower circulating lipid levels and ameliorate liver inflammation and steatosis. We here discuss the physiology of FGF21 and its role in lipid metabolism, with a focus on genetics, which has up until now not been fully appreciated.

Recent findings: New developments have uncovered associations of common small-effect variants of the FGF21 gene, such as the single nucleotide polymorphisms rs2548957 and rs838133, with numerous physiological, biochemical and behavioural phenotypes linked to energy metabolism and liver function. In addition, rare loss-of-function variants of the cellular receptors for FGF21 have been recently associated with severe endocrine and metabolic phenotypes. These associations corroborate the findings from basic studies and preliminary clinical investigations into the therapeutic potential of FGF21 for the treatment of metabolic dysfunction-associated steatotic liver disease (MASLD) and hypertriglyceridemia. Furthermore, recent breakthrough research has begun to dissect mechanisms of a potential FGF21 brain-adipose axis. Such inter-organ communication would be comparable to that seen with other potent metabolic hormones. A deeper understanding of FGF21 could prove to be further beneficial for drug development.

Summary: FGF21 is a potent regulator of lipid and energy homeostasis and its physiology is currently at the centre of investigative efforts to develop agents targeting hypertriglyceridemia and MASLD.

成纤维细胞生长因子 21:遗传学和分子生物学的最新进展。
综述的目的:自发现成纤维细胞生长因子 21(FGF21)以来,有关它的大多数研究都集中在其抗高血糖特性上。然而,最近人们的注意力已转向阐明成纤维细胞生长因子 21 降低循环血脂水平、改善肝脏炎症和脂肪变性的能力。我们在此讨论 FGF21 的生理学及其在脂质代谢中的作用,重点是遗传学,到目前为止,人们还没有充分认识到这一点:新的研究进展发现,FGF21 基因的常见小效应变异(如单核苷酸多态性 rs2548957 和 rs838133)与许多与能量代谢和肝功能有关的生理、生化和行为表型存在关联。此外,FGF21 细胞受体的罕见功能缺失变异最近也与严重的内分泌和代谢表型有关。这些关联证实了基础研究和初步临床研究的发现,FGF21 具有治疗代谢功能障碍相关性脂肪肝(MASLD)和高甘油三酯血症的潜力。此外,最近的突破性研究已开始剖析潜在的 FGF21 脑脂肪轴机制。这种器官间的交流可与其他强效代谢激素相媲美。对 FGF21 的深入了解将进一步促进药物开发:FGF21是脂质和能量平衡的有效调节剂,其生理学目前是针对高甘油三酯血症和MASLD开发药物的研究中心。
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来源期刊
Current opinion in lipidology
Current opinion in lipidology 医学-内分泌学与代谢
CiteScore
6.70
自引率
4.50%
发文量
64
审稿时长
6-12 weeks
期刊介绍: With its easy-to-digest reviews on important advances in world literature, Current Opinion in Lipidology offers expert evaluation on a wide range of topics from six key disciplines including nutrition and metabolism, genetics and molecular biology, and hyperlipidaemia and cardiovascular disease. Published bimonthly, each issue covers in detail the most pertinent advances in these fields from the previous year. This is supplemented by a section of Bimonthly Updates, which deliver an insight into new developments at the cutting edge of the disciplines covered in the journal.
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