Abstract

Klotho, a biomarker of aging, is associated with a slower aging process. Klotho concentration is lower among adults with obesity compared to normal-weight adults, and exercise may independently increase levels of Klotho. Whether Klotho is altered by weight loss and whether there is an added effect of exercise are not understood. PURPOSE: This study examined changes in Klotho concentration in response to a behavioral weight loss intervention among adults with overweight or obesity. METHODS: A subset of 152 adults (age: 45.4+8.0 years; BMI: 32.1+3.7 kg/m2) who participated in a 12-month weight loss intervention were classified as an intervention “responder” (achieved >10% weight loss at both 6- and 12 months) or “non-responder” (achieved <5% weight loss at both 6- and 12 months). Intervention conditions included: 1) diet only (1200-1800 kcal/day), 2) diet plus 150 min/wk of moderate-to-vigorous intensity physical activity (MVPA) per week, 3) or diet plus 250 min/wk of unsupervised MVPA per week. Measures of height, weight, body composition, cardiorespiratory fitness, and Klotho were completed at baseline, 6-, and 12 months. Klotho was analyzed using solid-phase sandwich ELISA kits. RESULTS: There were significant (p<0.0001) changes in weight (-12.5±9.1 kg), percent body fat (-7.1±5.5%), lean body mass (-1.7±2.0 kg), and cardiorespiratory fitness (+3.3±4.1 ml/kg/min) from baseline to 12-months. Klotho significantly (p=0.009) changed across the 12 months (baseline: 933±381 pg/mL; 6 months: 985±450 pg/mL; 12 months: 940±423 pg/mL), with no difference by intervention group or weight loss response. Participants who performed physical activity had non-significantly greater changes in Klotho. Klotho was consistently associated with lean body mass at baseline (r=-0.19), 6 (r=-0.23), and 12 months (r=-0.19) (p<0.05). Klotho was not predictive of change in weight, body composition, or fitness. CONCLUSION: Klotho significantly, but modestly, increases with weight loss; however, the increase in Klotho was not sustained throughout the intervention. There may be an influence of physical activity on change in Klotho with weight loss, but this warrants further investigation. Further investigation to examine how weight loss and physical activity may alter biomarkers of aging in adults with obesity may be warranted.

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