Elevated Circulating Fetuin-B Levels Are Associated with Insulin Resistance and Reduced by GLP-1RA in Newly Diagnosed PCOS Women

Abstract

Background. Previous studies have suggested that Fetuin-B seems to be a secreted adipokine related to metabolic diseases. However, the results have been inconsistent. Here, our objective is to investigate the changes in circulating Fetuin-B levels in women with polycystic ovary syndrome (PCOS) and analyze the association of Fetuin-B and insulin resistance (IR). Methods. The current study is comprised of a cross-sectional study and a series of interventional studies. Oral glucose tolerance test (OGTT) and euglycemic-hyperinsulinemic clamp (EHC) were engaged to assess glucose tolerance and insulin sensitivity. Serum Fetuin-B levels were determined by ELISA. Results. Serum Fetuin-B and TNF-α levels were markedly increased in women with PCOS compared to healthy women. Circulating Fetuin-B was positively associated with body mass index, waist-to-hip ratio, the percentage of body fat (FAT%), systolic blood pressure, triglyceride, low-density lipoprotein cholesterol, fasting blood glucose, 2 h blood glucose after glucose overload, fasting insulin, 2 h insulin after glucose overload, HOMA-insulin resistance index (HOMA-IR), the area under the curve for insulin (AUCi), AUCg, and TNF-α, while negatively associated with M value and follicular stimulating hormone (FSH). During the EHC, Fetuin-B levels were found to be significantly increased in PCOS women. After a glucose challenge, serum Fetuin-B levels in healthy women were significantly increased. Lipid infusion reduced serum Fetuin-B levels in 30 healthy subjects. After six months of glucagon-like peptide-1 receptor agonist (GLP-1RA) intervention, serum Fetuin-B concentrations in PCOS women markedly decreased following ameliorated IR. Conclusion. Our results indicate that Fetuin-B may be a biomarker of IR in individuals with PCOS. This trial is registered with ChiCTR-IIR-16007901.

DIA-Based Proteomic Analysis of Plasma Protein Profiles in Patients with Severe Acute Pancreatitis

“…FBLN1 is abundant in the plasma and arterial walls of patients with type 2 diabetes and can be used as a predictor of cardiovascular mortality in patients with type 2 diabetes [41]. An independent risk factor for type 2 diabetes is the plasma levels of AHSG, which is an insulin receptor inhibitor secreted by the liver and, along with FETUB [42,43], thought to be an important factor in insulin resistance in obesity [44,45]. GPLD1 serves as a biomarker that effectively differentiates latent autoimmune diabetes in adults from type 2 diabetes in the early stage [46], and it was shown that the circulating GPLD1 concentration in diabetic rats could be restored to normal levels by exercise training [47].…”

Ethinylestradiol in combined hormonal contraceptive has a broader effect on serum proteome compared with estradiol valerate: a randomized controlled trial

“…Untargeted proteomic analysis also enables the identification of interesting novel targets for future research. Fetuin-B is a relatively understudied hepatokine associated with insulin resistance, dyslipidemia, and non-alcoholic fatty liver disease ( Meex and Watt, 2017 ; Mokou et al , 2020 ; Olkowicz et al , 2021 ). Serum levels of fetuin-B increase during pregnancy but normalize after delivery ( Šimják et al , 2018 ), possibly related to hormonal changes of pregnancy.…”

High Fat, High Sugar Diet and DJOS Bariatric Surgery Influence Plasma Levels of Fetuin-B, Growth Differentiation Factor-15, and Pentraxin 3 in Diet-Induced Obese Sprague–Dawley Rats

“…When analyzing our OGTT results, we can see that the glycemia is also much higher in rats fed with the HSF diet before or after the DJOS surgery. Mokou et al [ 28 ], in their study on women with polycystic ovarian syndrome (PCOS), showed elevated levels of fetuin-B in the serum of the studied subjects. Moreover, they found that fetuin-B concentration in the serum was even higher in obese subjects when compared with those without this comorbidity.…”

“…Moreover, they found that fetuin-B concentration in the serum was even higher in obese subjects when compared with those without this comorbidity. Therefore, they suggested that fetuin-B might be associated with indicators of lipid and glucose metabolism and markers of inflammation [ 28 ]. On the other hand, Xing et al [ 29 ] reported that the elevated levels of fetuin-B could be at least partly associated with the higher risk of myocardium ischemia.…”