Pubertal FGF21 deficit is central in the metabolic pathophysiology of an ovine model of polycystic ovary syndrome. Siemienowicz KJ et al. (2021) Polycystic ovary syndrome (PCOS), affecting over 10% of women, is associated with insulin resistance, obesity, dyslipidaemia, fatty liver and adipose tissue dysfunction. Its pathogenesis is poorly understood and consequently treatment remains suboptimal. Prenatally androgenized (PA) sheep, a clinically realistic model of PCOS, recapitulate the metabolic problems associated with PCOS. Fibroblast Growth Factor 21 (FGF21) is a metabolic hormone regulating lipid homeostasis, insulin sensitivity, energy balance and adipose tissue function. We therefore investigated the role of FGF21 in the metabolic phenotype of PA sheep. In adolescence PA sheep had decreased hepatic expression and circulating concentrations of FGF21. Adolescent PA sheep show decreased FGF21 signalling in subcutaneous adipose tissue, increased hepatic triglyceride content, trend towards reduced fatty acid oxidation capacity and increased hepatic expression of inflammatory markers. These data parallel studies on FGF21 deficiency, suggesting that FGF21 therapy during adolescence may represent a treatment strategy to mitigate metabolic problems associated with PCOS.//////////////////
NCBI Summary:
Theis gene encodes a member of the fibroblast growth factor (FGF) family. FGF family members possess broad mitogenic and cell survival activities and are involved in a variety of biological processes. This protein is a secreted endocrine factor that functions as a major metabolic regulator. The encoded protein stimulates the uptake of glucose in adipose tissue. [provided by RefSeq, Mar 2016]
General function
Ligand, Growth factor
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Cellular localization
Secreted
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Ovarian function
Comment
Fibroblast growth factor 21 coordinates adiponectin to mediate the beneficial effects of low-protein diet on primordial follicle reserve. Zhuo Y et al. (2019) Global consumption of protein per capita is rising, while rates of infertility are increasing. However, a clear relationship between protein intake and reproductive health has not been demonstrated. The activation of the quiescent primordial follicles is the first step of folliculogenesis, and their activation must be tightly controlled to prevent premature exhaustion of the ovarian follicular reserve. The primordial follicle reserve of wild-type or liver-specific ablation of fibroblast growth factor 21 (FGF21) in mice, subjected to limited or excessive protein diets or oral gavage test, were detected in vivo. Mouse ovary organ cultures were used to examine the direct role of metabolites or metabolic hormones on primordial follicle activation. Mouse primordial follicle activation, was reduced by restricted protein intake and was accelerated by excessive protein intake, in an ovarian mTORC1 signaling-dependent manner. Furthermore, restricted or excessive protein intake resulted in an augmentation or decline of oocyte number and fertility at older age, respectively. Liver-specific ablation of FGF21, which resulted in a reduction of 87% in circulating FGF21, abrogated the preserving effect of low-protein intake on primordial follicle pool. Interestingly, FGF21 had no direct effect on the activation of primordial follicles, but instead required an adipokine adiponectin. Moreover, AdipoRon, an oral adiponectin receptor agonist, prevented the over-activation effect of excessive protein intake on primordial follicle activation. Dietary protein consumption controlled ovarian primordial follicle reserve and fertility, which required coordination between FGF21 and adiponectin. FUND: Natural Science Foundation of China (Grant 31772616).//////////////////
Fibroblast growth factor 21 and its relation to metabolic parameters in women with polycystic ovary syndrome. Sahin SB 2014 et al.
Objective. The aim of this study was to compare the serum levels of fibroblast growth factor 21 (FGF-21) between patients with polycystic ovary syndrome (PCOS) and control subjects and to assess the possible relation with the hormonal and metabolic parameters. Methods. A total of 91 patients with PCOS and 53 age- and body mass index (BMI)-matched healthy controls were included in the study. We evaluated anthropometric, hormonal and metabolic parameters in all the cases. Serum FGF-21 and high sensitive C-reactive protein (hsCRP) levels were measured by ELISA. Results. Mean fasting glucose and insulin, homeostasis model assessment insulin resistance index (HOMA-IR), triglyceride, total cholesterol, low density lipoprotein cholesterol, total testosterone, dehydroepiandrosterone sulfate (DHEAS) levels were significantly higher in PCOS patients. Serum FGF-21 levels were similar in PCOS (236.8 171.2 pg/ml) and the control (224.6 128.9 pg/ml) group (p = 0.654). FGF-21 level had no correlation with BMI, waist circumference, HOMA-IR, hsCRP and lipid parameters. However there was a significant negative correlation between FGF-21 and DHEAS levels (r = - 0.309, p = 0.003). Conclusion. FGF-21 levels were similar in women with PCOS compared with those of age- and BMI- matched controls.
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Expression regulated by
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Ovarian localization
Comment
Serum fibroblast growth factor 21 levels in polycystic ovary syndrome. Gorar S et al. Aim. This study was designed to measure serum fibroblast growth factor 21 (FGF21) levels in patients with polycystic ovary syndrome (PCOS) and healthy subjects. Methods. A total of 37 women were evaluated. Serum levels FGF21, glucose, lipid profile, hormones (follicle-stimulating hormone, luteinising hormone, oestradiol, testosterone, thyroid stimulating hormone, prolactin and insulin) were determined in 24 PCOS (15 subjects of PCOS BMI < 25 kg/m(2), 9 subjects of PCOS BMI >/= 25 kg/m(2)) and 13 control group (BMI < 25 kg/m(2)). Results. Serum FGF21 levels were higher in the PCOS group [99.5 (173.7) pg/ml] than in the control group [52.0 (88.0) pg/ml]. LH and T are significantly higher in PCOS cases (respectively; p < 0.05, p < 0.01). A positive correlation was found between FGF21 and luteinising hormone and testosterone (respectively; r = 0.43 p = 0.007, r = 0.38, p = 0.02). Multivariate discriminant analysis showed that BMI, triglyceride, HOMA-IR, fasting glucose with rise of FGF21 were found significant in PCOS. Conclusion. Our study indicates that FGF21 in cases with PCOS exhibit an increase along with the increase of BMI and also has a positive correlation with LH and T. Further studies are required to clarify the aetiology and effects of FGF21 in women with PCOS.
Follicle stages
Comment
Phenotypes
PCO (polycystic ovarian syndrome)
Mutations
1 mutations
Species: mouse
Mutation name: type: null mutation fertility: subfertile Comment: FGF21 induces PGC-1alpha and regulates carbohydrate and fatty acid metabolism during the adaptive starvation response. Potthoff MJ et al. (2009) The liver plays a crucial role in mobilizing energy during nutritional deprivation. During the early stages of fasting, hepatic glycogenolysis is a primary energy source. As fasting progresses and glycogen stores are depleted, hepatic gluconeogenesis and ketogenesis become major energy sources. Here, we show that fibroblast growth factor 21 (FGF21), a hormone that is induced in liver by fasting, induces hepatic expression of peroxisome proliferator-activated receptor gamma coactivator protein-1alpha (PGC-1alpha), a key transcriptional regulator of energy homeostasis, and causes corresponding increases in fatty acid oxidation, tricarboxylic acid cycle flux, and gluconeogenesis without increasing glycogenolysis. Mice lacking FGF21 fail to fully induce PGC-1alpha expression in response to a prolonged fast and have impaired gluconeogenesis and ketogenesis. These results reveal an unexpected relationship between FGF21 and PGC-1alpha and demonstrate an important role for FGF21 in coordinately regulating carbohydrate and fatty acid metabolism during the progression from fasting to starvation.//////////////////
Defective luteal function