Association between Soluble α-Klotho Protein and Metabolic Syndrome in the Adult Population

Klotho protein is an anti-aging protein and plays multiple roles in ion-regulation, anti-oxidative stress, and energy metabolism through various pathways. Metabolic syndrome is a combination of multiple conditions that compose of multiple risk factors of cardiovascular disease and type 2 diabetes. Gene regulation and protein expression are discovered associated with metabolic syndrome. We aimed to figure out the correlation between Klotho protein and metabolic syndrome in generally healthy adults. A cross-sectional study of 9976 respondents ≥ 18 years old from the US National Health and Nutrition Examination Survey (2007–2012) by utilizing their soluble Klotho protein concentrations. Multivariate linear regression models were used to analyze the effect of soluble Klotho protein on the prevalence of metabolic syndrome. Soluble Klotho protein concentration was inversely correlated with the presence of metabolic syndromes (p = 0.013) and numbers of components that met the definition of metabolic syndrome (p < 0.05). The concentration of Soluble Klotho protein was negatively associated with abdominal obesity and high triglyceride (TG) in the adjusted model (p < 0.05). Soluble Klotho protein is correlated with changing metabolic syndrome components in adults, especially central obesity and high TG levels. Despite conventional function as co-factor with fibroblast growth factor-23 (FGF23) that regulates phosphate and vitamin D homeostasis, FGF23-independent soluble Klotho protein may act on multiple signal pathways in different organs and tissue in roles of anti-aging and protection from metabolic syndrome.

Role of Klotho as a Modulator of Oxidative Stress Associated with Ovarian Tissue Cryopreservation

Ovarian tissue cryopreservation is the only option for preserving fertility in adult and prepubertal cancer patients who require immediate chemotherapy or do not want ovarian stimulation. However, whether ovarian tissue cryopreservation can ameliorate follicular damage and inhibit the production of reactive oxygen species in cryopreserved ovarian tissue remains unclear. Oxidative stress is caused by several factors, such as UV exposure, obesity, age, oxygen, and cryopreservation, which affect many of the physiological processes involved in reproduction, from maturation to fertilization, embryonic development, and pregnancy. Here, freezing and thawing solutions were pre-treated with N-acetylcysteine (NAC) and klotho protein upon the freezing of ovarian tissue. While both NAC and klotho protein suppressed DNA fragmentation by scavenging reactive oxygen species, NAC induced apoptosis and tissue damage in mouse ovarian tissue. Klotho protein inhibited NAC-induced apoptosis and restored cellular tissue damage, suggesting that klotho protein may be an effective antioxidant for the cryopreservation of ovarian tissue.

Fibroblast growth factor 23 and Klotho protein: assessment of the role in the development of secondary hyperparathyroidism in patients with various stages of chronic kidney disease

Background. Secondary hyperparathyroidism (SHPT) is universal complication of chronic kidney disease (CKD), the likelihood of which increases as renal function decreases. Currently, SHPT is considered in the context of mineral and bone disorders associated with CKD. Mineral and bone disorders associated with CKD include, in addition to SHPT, disorders of calcium-phosphorus metabolism, bone pathology and metastatic calcification, which determine poor outcomes of the disease. The purpose of the study was to evaluate the serum concentrations of fibroblast growth factor (FGF) 23 and Klotho protein in patients with various stages of CKD and their relationship with SHPT, vitamin D levels, and calcium-phosphorus metabolism in patients with varying degrees of decreased renal function. Materials and methods. Serum concentrations of FGF 23, Klotho protein, parathyroid hormone (PTH), 25(OH)D, calcium and phosphorus were evaluated in 229 patients with various stages of chronic kidney disease and in 40 people without signs of CKD. Results. It has been shown that individuals with CKD are characterized by overproduction of humoral phosphatonin FGF 23 and Klotho deficiency, which increase as renal failure worsens. A significant relationship was established between FGF 23 and the levels of PTH and blood phosphorus; Klotho protein — with the patient’s age and serum vitamin D. An early marker of disorders in the FGF 23-Klotho system is a decrease in the Klotho protein concentration, which occurs in the early stages of CKD and is aggravated with the progression of renal failure. A statistically significant overproduction of FGF 23 associated with secondary hyperparathyroidism was registered in patients with glomerular filtration rate less than 35 ml/min/1.73 m2. Conclusions. An early marker of disorders in the FGF 23-Klotho system is a decrease in the concentration of the Klotho protein, which occurs in the early stages of CKD and is aggravated with the progression of renal fai-lure. The relationship between Klotho deficiency and the formation of SHPT has not been found. As kidney function decreases, excess production of PTH and FGF 23 appears and increases, hyperphosphatemia progresses. This proves the pathogenetic relationship between the formation of SHPT and the overproduction of humoral phosphatonin FGF 23, since it is this glomerular filtration rate that determines the growth of PTH above the upper limit of the general population reference interval.

Кlotho protein level in patients with myocardial infarction and chronic obstructive pulmonary disease in relation to the number of stenosis

Introduction. The clinical course and outcome in patients with comorbid pathology has a number of features that require further investigation. The investigation of biomarkers is important in this area as any change in their levels reflects the severity of pathogenetic changes and has prognostic value. Cardiovascular disease (CVD) and chronic obstructive pulmonary disease (COPD) are one of the most frequently reported comorbid pathologies. This is due to a large number of common interrelated links of pathogenesis and risk factors.The aim of the study. To study and analyze, in a comparative aspect, the level of Klotho protein in patients with MI and patients with MI and COPD, in relation to the number of stenosis of coronary arteries (CA) according to coronary angiography.Materials and methods. 110 patients were examined, divided into two groups: the main group - patients with MI on the background of COPD (n = 60) and the comparison group – patients with MI (n = 50). Somatically healthy individuals (n = 30) were examined as a control group. Determination of Klotho protein level in plasma samples was carried out by enzyme-linked immunosorbent assayResults. It was found that in patients with MI and COPD, the level of Klotho protein was statistically significantly lower than in the control group and in patients with MI. The relationship between the Klotho protein level and lipid profile parameters was revealed in both patients with MI and patients with MI and COPD, with a greater strength of relationships in patients with comorbid pathology. It was also found that in the group of patients with comorbid pathology in individuals with lesions of one, two, three or more CA, the Klotho level was statistically significantly lower than in patients with MI with the corresponding number of affected CA.Conclusions. The results obtained prove the promise and the need for further study of the pathogenetic role of the Klotho protein level in patients with comorbid pathology.

Soluble Klotho Is Decreased in Children With Type 1 Diabetes and Correlated With Metabolic Control

Klotho concentration may be considered as a prognostic factor in the development of chronic complications of diabetes. Moreover, decrease in sKlotho concentration may contribute to beta cell apoptosis and type 1 diabetes development. The aim of this study was to evaluate if sKlotho protein concentration in children with type 1 diabetes (T1D) and its correlation with classical risk factors of chronic complications of diabetes: dysglycemia and endothelial dysfunction.Material and methodsIn a cross-section single center study the levels of soluble Klotho protein in 80 T1D (37 boys) and 34 healthy children (controls, 15 boys). Micro- and macroangiopathy were excluded and renal function was normal in all participants. Serum sKlotho, sICAM-1, sVCAM-1 and E-selectin levels were measured.ResultsThe concentration of sKlotho was lower in T1D than in the controls (2041.9 ± 1017.6 pg/mL vs. 2790.3 ± 1423.9 pg/mL, p=0.0113). sICAM-1, sVCAM-1 and E-selectin concentrations were comparable in patients and controls. In T1D, sKlotho was not correlated with the duration of diabetes. Klotho and E-selectin were correlated with HbA1c (r=-0.31, P=0.0066 and r=0.25, P=0.0351, respectively), but not with AVBG and blood glucose SD. Correlations of sKlotho with total cholesterol (r=0.31, P=0.0129), HDL-cholesterol (r=0.43, P=0.0011) and LDL-cholesterol (r=0.28, P=0.0412), but not with triglycerides, were found. Likewise, Klotho was not correlated with sICAM-1, sVCAM-1, and E-selectin concentrations.ConclusionsThis study reports the significantly lower level of s-Klotho in children with type 1 diabetes, correlated with HbA1c and HDL cholesterol, but not with the adhesion molecules concentrations nor the duration of the disease. Negative correlation between the levels of HbA1c and soluble Klotho may suggest its possible involvement in the development of chronic diabetes complications.

Analysis of Klotho Protein Level in Patients with Myocardial Infarction and Concurrent Chronic Obstructive Pulmonary Disease with Different Manifestations

The objective: to compare the level of Klotho protein in patients with myocardial infarction (M I) and concurrent chronic obstructive pulmonary disease (COPD) and patients with COPD only with consideration of specific manifestations of COPD (severity of symptoms and risk of exacerbations).Subjects and Methods. 144 patients were examined and divided into the following groups: MI + COPD Group - patients with MI and concurrent COPD (60 patients), COPD Group - patients with COPD (54 patients) and HI Group - somatically healthy individuals (30 people). The patients were divided into subgroups (A, B, C, D) according to the GOLD 2019 classification. Enzyme immunoassay was used to test the level of Klotho.Results. A statistically significant lower level of Klotho was detected in patients in MI + COPD Group compared to COPD Group and healthy individuals. Patients in the subgroups with severe symptoms (B and D) in both the COPD and MI + COPD Groups had statistically significantly lower levels of Klotho compared to those in the subgroups with no symptoms (A and C). Among patients with MI + COPD in subgroups A, B, C, D, the Kloto level was statistically significantly lower versus the patients of the corresponding subgroups in COPD Group. The lowest level of Klotho was detected in MI + COPD and COPD Groups in patients of subgroup D, that was in patients with severe symptoms and frequent exacerbations of COPD. The data obtained were confirmed by correlation analysis results. It was found that in MI + COPD and COPD Groups, the level of Klotho had a negative correlation with both the severity of symptoms and number of COPD exacerbations. Correlations were the strongest between the level of Klotho and parameters characterizing the severity of COPD symptoms.