Insulin resistance, renal injury, renal 1-alpha hydroxylase, and bone homeostasis in aged obese rats

Abstract

Background: This study aimed to explore the relationship among insulin resistance (IR), renal injury, renal 1-alpha hydroxylase activity (RHA), and bone homeostasis in the presence of obesity.

Methods: Obesity, obesity treated with vitamin D, and obesity treated with 1-alpha hydroxyvitamin D [1-alpha(OH)D] were studied in animal models using aged Wistar rats. Glucose infusion rates (GIR), levels of urinary albumin (UA), serum 25-hydroxyvitamin D [25-(OH)D], serum 1,25-dihydroxyvitamin D [1,25(OH)(2)D], and bone mineral density (BMD) in lumbar vertebrae and femoral bone were measured.

Results: GIR in obese rats decreased. A negative correlation existed between UA level and GIR in the aged obese rats, which did not exist in the normal control rats. Levels of serum 25(OH)D in all models were similar. Obese rats had lower levels of serum 1,25(OH)(2)D and BMD than normal control rats. Treating obese rats with vitamin D had no effect on levels of serum 25-(OH)D, serum 1,25(OH)(2)D, and BMD. Administration of 1alpha-(OH)D to obese rats significantly increased serum 1,25(OH)(2)D to above-normal levels and BMD to normal level. In obese rats, levels of serum 1,25(OH)(2)D and BMD in lumbar vertebrae and femoral bone were positively correlated with GIR, and the level of serum 1,25(OH)(2)D was negatively correlated with the UA level.

Conclusions: In the presence of obesity, IR, renal injury, decrease in RHA and bone loss exist. IR-injured kidney accounts for a decrease in RHA, which is a precipitating factor for bone loss.