Qatar Metabolic Institute, Interim Translational Research Institute, Academic Health System, Hamad Medical Corporation, Doha, Qatar.
Department of Academic Endocrinology, Diabetes and Metabolism, Hull York Medical School, Hull, United Kingdom.
Front Endocrinol (Lausanne). 2020 Sep 30;11:568500. doi: 10.3389/fendo.2020.568500. eCollection 2020.
The fibroblast growth factors (FGF) 19 subfamily, also referred to as endocrine FGFs, includes FGF19, FGF21, and FGF23 are metabolic hormones involved in the regulation of glucose and lipid metabolism. Fetuin-A is a hepatokine involved in the regulation of beta-cell function and insulin resistance. Endocrine FGFs and fetuin-A are dysregulated in metabolic disorders including obesity, type 2 diabetes, non-alcoholic fatty liver disease and polycystic ovary syndrome (PCOS). Our study was designed to examine the response of endocrine FGFs and fetuin-A to an acute intralipid, insulin infusion and exercise in PCOS and healthy women. Ten healthy and 11 PCOS subjects underwent 5-h saline infusions with a hyperinsulinemic-euglycemic clamp (HIEC) performed during the final 2 h. One week later, intralipid infusions were undertaken with a HIEC performed during the final 2 h. After an 8 week of exercise intervention the saline, intralipid, and HIEC were repeated. Plasma levels of endocrine FGFs and fetuin-A were measured. Baseline fetuin-A was higher in PCOS women but FGF19, FGF21, and FGF23 did not differ and were unaffected by exercise. Insulin administration elevated FGF21 in control and PCOS, suppressed FGF19 in controls, and had no effects on FGF23 and fetuin-A. Intralipid infusion suppressed FGF19 and increased FGF21. Insulin with intralipid synergistically increased FGF21 and did not have effects on lipid-mediated suppression of FGF19 in both groups. Our study provides evidence for insulin and lipid regulation of endocrine FGFs in healthy and PCOS women, suggesting that FGF family members play a role in lipid and glucose metabolism. www.isrctn.org, Identifier: ISRCTN42448814.
成纤维细胞生长因子（FGF）19 亚家族，也称为内分泌 FGFs，包括 FGF19、FGF21 和 FGF23，是参与调节葡萄糖和脂质代谢的代谢激素。胎球蛋白-A 是一种参与调节胰岛功能和胰岛素抵抗的肝分泌因子。内分泌 FGFs 和胎球蛋白-A 在代谢紊乱中失调，包括肥胖、2 型糖尿病、非酒精性脂肪性肝病和多囊卵巢综合征（PCOS）。我们的研究旨在检查内分泌 FGFs 和胎球蛋白-A 对 PCOS 和健康女性中急性脂肪乳剂、胰岛素输注和运动的反应。10 名健康女性和 11 名 PCOS 患者接受了 5 小时盐水输注，并在最后 2 小时进行高胰岛素-正常血糖钳夹（HIEC）。一周后，进行脂肪乳输注，并在最后 2 小时进行 HIEC。经过 8 周的运动干预后，重复进行盐水、脂肪乳和 HIEC。测量内分泌 FGFs 和胎球蛋白-A 的血浆水平。基础胎球蛋白-A 在 PCOS 女性中更高，但 FGF19、FGF21 和 FGF23 没有差异，并且不受运动影响。胰岛素给药增加了对照组和 PCOS 患者的 FGF21，抑制了对照组的 FGF19，对 FGF23 和胎球蛋白-A 没有影响。脂肪乳输注抑制了 FGF19，并增加了 FGF21。胰岛素与脂肪乳协同增加了 FGF21，并且对两组中脂质介导的 FGF19 抑制没有影响。我们的研究为健康和 PCOS 女性中胰岛素和脂质对内分泌 FGFs 的调节提供了证据，表明 FGF 家族成员在脂质和葡萄糖代谢中发挥作用。www.isrctn.org，标识符：ISRCTN42448814。
