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

Abstract

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.

Comment on: Alpha-Klotho protein in systemic lupus erythematosus

“…Furthermore, this study also demonstrated that obesity may be closely related to serum alpha-Klotho levels (beta coefficient, 95% confidence interval: 0.66, 0.2-1.11, p=0.005) (1). The close relationship of obesity and serum alpha-Klotho has also been reported in a previous study (5). Therefore, the effect of obesity on the results of this study cannot be ruled out.…”

The Association of Obesity and the Antiaging Humoral Factor Klotho in Middle-Aged and Older Adults

“…Likewise, serum klotho levels were negatively correlated with waist circumference and BMI among women aged 19–33 years with polycystic ovary syndrome [ 15 ]. A recent large analysis of the NHANES also demonstrated significantly lower serum klotho levels among participants with abdominal obesity than those without [ 16 ]. The present results extend those from previous research by reporting that prevalent general and abdominal obesity were significantly associated with lower klotho levels only in women.…”

“…In contrast, young Japanese women with restrictive-type anorexia nervosa or obesity had significantly lower serum klotho levels than those with a healthy body weight [14]. Recent studies also demonstrated that serum klotho levels were negatively correlated with waist circumference in young women with polycystic ovary syndrome and among community-dwelling adults with abdominal obesity [15][16][17]. Whether the obesity history is associated with lower klotho levels has not been previously explored.…”

The Klotho-FGF23 axis and cardiovascular outcomes in diabetic patients with chronic limb threatening ischemia: a prospective study

“…Interestingly, increased levels of Klotho reduce oxidative damage after myocardial infarction in animal models 40 . Furthermore, reduced Klotho levels are also associated with central obesity, elevated triglycerides, and metabolic syndrome 41 . Not surprisingly, reduced Klotho levels and elevated FGF23 concentrations have been associated with increased hospitalizations for heart failure and the incidence of cardiovascular death in a population of 3555 patients with stable ischemic heart disease 42 .…”