Exercise attenuates bed rest-induced increases in insulin resistance while α-klotho increases in 55 to 65 year-old women and men

Abstract

We evaluated the efficacy of combined aerobic, high intensity interval (HIIT) and resistive exercises during Head-Down Bed Rest (HDBR) in preventing metabolic derangement. Twenty-two participants (control: F (5) BMI: 22.1 ± 2.1, M (6) BMI: 25.7 ± 2.2, exercise F (6) BMI: 24.3 ± 3.2, M (5) BMI: 27.5 ± 1.2; Average age: 59 ± 3 years; weight: 70.1 ± 14.2 kg; height: 1.67 ± 0.09 m; BMI: 24.9 ± 3.0 kg/m²)) confined to 6° HDBR for 14-days were randomly assigned to either EX (1 h/day head-down exercise including HIIT every other day) or CONT (passive movement). Oral glucose tolerance tests (OGTT) at baseline, day 9 HDBR (HDT 9) and 13 HDBR (HDT 13) were matched to fasted biomarker analyses and Vastus lateralis biopsies. HDBR increased area under the curve for glucose (p < 0.01, interaction between groups; group × bed rest; p = 0.07) and insulin (p < 0.01). Matsuda index fell in CONT alone, FGF-23 increased in EX correlating with elevations to circulating levels of C reactive protein; a negative correlation existed between FGF-23 and HOMA-IR in CONT. A novel finding was that α-klotho increased in all participants (p < 0.0001), starting higher and rising faster in women, whilst negatively correlating with Matsuda index in CONT alone. Undercarboxylated-osteocalcin ratio fell in CONT (p = 0.05). Neither IGF-1, nor GLUT1/4 protein content changed during HDBR. HDBR promoted insulin resistance with increases in circulating α-klotho; FGF-23 increased only in EX. Differing Matsuda index responses indicate benefits imparted by multimodal exercise despite elevations in α-klotho and FGF-23.Clinical Trial Registration Number: NCT04964999.

Keywords: Exercise countermeasure; Head down bed rest; Insulin resistance; Oral glucose tolerance test; α-Klotho.

Fig. 1

Glucose (A) and insulin (B) area under the curve (AUC), QUICKI (C), HOMA-IR (D), ISI_(0,120) (E), and Matsuda Index (F) for CONT (left) and EX (right) at HDT-2, HDT 9 and HDT 13. Individual participant data are superimposed on the median and interquartile ranges.

Fig. 2

Intact FGF-23 concentrations (A) for CONT (left) and EX (right) at HDT-2, HDT 9 and HDT 15. Individual participant data are superimposed on the median and interquartile ranges, with circles representing women and triangles representing men. Repeated measures correlations between FGF-23 and hsCRP (B and C) and FGF-23 and Serum Phosphate (D and E).

Fig. 3

Biomarker changes during HDBR. Soluble α-klotho plasma concentrations (A) for CONT (left) and EX (right) at HDT-2, HDT 9 and HDT 15. For ease of viewing these same data are presented following grouping by sex (B); women (left) and men (right). Individual participant data are superimposed on the median and interquartile ranges, with circles representing women and triangles representing men. Total osteocalcin (C), undercarboxylated osteocalcin (D) and undercarboxylated osteocalcin ratio (E) for CONT (left) and EX (right) at HDT-2, HDT 9 and HDT 13. Individual participant data are superimposed on the median and interquartile ranges.

Fig. 4

Repeated Measures Correlations between α-klotho and Insulin Sensitivity Index ((ISI_(0,120)), A, B) and Matsuda index (C, D), for CONT (left) and EX (right). Individual participant data are provided with circles representing HDT-2 and squares representing HDT 9.