J Nutr Health.  2023 Feb;56(1):1-11. 10.4163/jnh.2023.56.1.1.

Effect of cinacalcet-mediated parathyroid hormone reduction on vitamin D metabolism in high-fat dietinduced obese mice

• Kim TY
• Park CY
• Han SN

• KMID: 2540103
• DOI: http://doi.org/10.4163/jnh.2023.56.1.1

Abstract

Purpose
Obesity is associated with alterations in vitamin D metabolism and elevation of parathyroid hormone (PTH). Increased PTH level in obesity is likely one of the factors contributing to the dysregulation of vitamin D metabolism. We investigated the effects of lowering the PTH level in high-fat diet-induced obese mice on vitamin D metabolism.
Methods
Five-week-old male C57BL/6N mice were fed either with control (10% energy as fat) or high-fat (60% energy as fat) diets ad libitum for 12 weeks, and vehicle or cinacalcet HCl (30 μg/g body weight) was gavaged daily during the final week of the experiment. The following groups were studied: CON (control diet + vehicle), HFD (high-fat diet + vehicle), and HFD-CIN (high-fat diet + cinacalcet HCl). PTH, 1,25-dihydroxyvitamin D (1,25[OH] 2 D), 25-hydroxyvitamin D (25[OH]D), calcium, and phosphate levels in circulation, and the expression of genes related to vitamin D metabolism in the liver and kidneys were determined.
Results
Renal 1α-hydroxylase expression in the HFD group was higher than that in the CON group despite the lack of a difference in the PTH levels between the 2 groups. The plasma PTH level in the HFD-CIN group was 60% lower than that in the HFD group (p < 0.05). In parallel, the HFD-CIN group had lower adipose tissue amount (9% lower), renal 1α-hydroxylase expression (48% lower), and plasma 1,25(OH) 2 D concentration (38% lower) than the HFD group.
Conclusion
Lowering the PTH levels in high-fat diet-induced obese mice recovered the expression of renal 1α-hydroxylase and might be associated with lower amounts of white adipose tissue.

Keyword

parathyroid hormone; 1,25-dihydroxyvitamin D; 25-Hydroxyvitamin D3 1-alphaHydroxylase; Vitamin D3 24-Hydroxylase; obesity