Alteration in serum klotho levels in anorexia nervosa patients

Abstract

Klotho is a trans-membrane protein which can be shed to act as a hormone; its blood levels may be regulated by the GH/IGF-1 axis. Klotho deficient mice exhibit short lifespan and characteristics of aging and malnutrition, including decreased fat and muscle mass, osteopenia, and impaired fertility. As anorexia nervosa (AN) is characterized by malnutrition and GH resistance, we hypothesized klotho levels would be altered in AN, and aimed to assess klotho levels in undernourished AN patients and changes in klotho following weight rehabilitation. 19 adolescent female AN inpatients (aged 16.1±1.8 years) admitted to an inpatient service for eating disorders in a tertiary center were recruited. Blood samples were obtained on admission and after weight restoration (interval 4.0±2.3 months) and analyzed for klotho, IGF-1, calcium, phosphorus, and alkaline phosphatase. Klotho levels on admission were lower than expected for age, and correlated with lumbar spine BMD Z-score (r=-0.81, p<0.001) and alkaline phosphatase levels (r=0.66, p=0.003) but not with age, height-SDS, weight-SDS, BMI-SDS, or serum calcium, phosphorus and IGF-1 levels. Both IGF-1 and klotho levels increased significantly during hospitalization (IGF-1: 44±17nmol/l to 53±11nmol/l, p=0.008; klotho: 1061±421pg/ml to 1519±781pg/ml, p=0.008). Klotho levels are low in the acute stage of AN and increase with nutritional rehabilitation. Low klotho on admission may be secondary to low IGF-1 levels and may contribute to the clinical manifestations of AN. The role of klotho in the pathophysiology of AN and as a novel marker of disease severity should be further explored.