Dynamic Changes in Circulating Endocrine FGF19 Subfamily and Fetuin-A in Response to Intralipid and Insulin Infusions in Healthy and PCOS Women

Abstract

Background: 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. Subjects and Measurements: 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. Results: 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. Conclusion: 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.

Effect of Moderate Aerobic Exercise on Complement Activation Pathways in Polycystic Ovary Syndrome Women

“…During each exercise session, heart rate and inspired/expired gas fractions were continuously monitored and heart rate equivalent to 60% of baseline VO 2max was achieved during each session of exercise training ( 27 ). Insulin sensitivity was measured using the gold standard euglycemic clamp technique as described previously ( 28 , 29 ). Within a week following the completion of exercise protocol, all participants were invited to provide blood samples and underwent insulin sensitivity test.…”

Diagnostic Value of Bile Acids and Fibroblast Growth Factor 21 in Women with Polycystic Ovary Syndrome

“… 28 , 33 , 34 FGF-19 levels have been published as decreased or unchanged in patients with PCOS. 27 As our recruitment population was from an underserved rural area with high levels of diabetes and obesity, it is possible that distribution patterns of bile acids are affected heterogeneously depending on environmental queues.…”

The Role of Fibroblast Growth Factor 19 Subfamily in Different Populations Suffering From Osteoporosis

“…FGF-21 plays a key role in the metabolic process as a hepatic, adipokine and myokine. It appears to function through FGFR1c-mediated binding to β-klotho to form complexes ( 21 ). Circulating FGF21 is primarily expressed by the liver when the body is starving, obese, mitochondrial dysfunction and aging, while FGF21 expression is barely detectable in healthy conditions ( 22 ).…”

“…FGF-21 is mainly expressed by the liver and acts as a potent activator of glucose uptake by inducing glucose transporter 1 (GLUT1) on adipocytes, which reverses hepatic steatosis and improves insulin sensitivity in obese mice ( 67 ). A study on the effect of insulin on endocrine FGFs in women with PCOS found that insulin administration increased plasma levels of FGF-21 in healthy controls and women with PCOS, suppressed plasma levels of FGF-19 in healthy controls, and had no effect on plasma levels of FGF-23 ( 21 ). An earlier study evaluated FGF-21 levels in PCOS and found that circulating FGF-21 levels were higher in PCOS patients and correlated with homeostasis model assessment insulin resistance index (HOMA-IR) ( 68 ).…”