Gene Expression Laboratory, Salk Institute for Biological Studies, La Jolla, CA, USA.
Nat Metab. 2022 Jun;4(6):663-671. doi: 10.1038/s42255-022-00580-2. Epub 2022 Jun 9.
While fibroblast growth factor (FGF) 1 is expressed in multiple tissues, only adipose-derived and brain FGF1 have been implicated in the regulation of metabolism. Adipose FGF1 production is upregulated in response to dietary stress and is essential for adipose tissue plasticity in these conditions. Similarly, in the brain, FGF1 secretion into the ventricular space and the adjacent parenchyma is increased after a hypercaloric challenge induced by either feeding or glucose infusion. Potent anorexigenic properties have been ascribed to both peripheral and centrally injected FGF1. The ability of recombinant FGF1 and variants with reduced mitogenicity to lower glucose, suppress adipose lipolysis and promote insulin sensitization elevates their potential as candidates in the treatment of type 2 diabetes mellitus and associated comorbidities. Here, we provide an overview of the known metabolic functions of endogenous FGF1 and discuss its therapeutic potential, distinguishing between peripherally or centrally administered FGF1.
成纤维细胞生长因子（FGF）1 在多种组织中表达，但只有脂肪组织来源的和大脑中的 FGF1 被认为参与了代谢的调节。脂肪组织 FGF1 的产生在应对饮食压力时会被上调，这对于这些情况下脂肪组织的可塑性是必不可少的。同样，在大脑中，在通过进食或葡萄糖输注引起的高热量挑战后，FGF1 会被分泌到脑室空间和相邻的实质中。外周和中枢注射 FGF1 都具有强烈的厌食作用。重组 FGF1 及其具有降低有丝分裂活性的变体降低葡萄糖、抑制脂肪分解并促进胰岛素敏感性的能力，提高了它们作为 2 型糖尿病及其相关合并症治疗候选药物的潜力。在这里，我们提供了内源性 FGF1 的已知代谢功能概述，并讨论了其治疗潜力，区分了外周或中枢给予的 FGF1。
