Dietary calcium intake controls epithelial expression of TRPV6 independent of 1,25(OH)2D3 endocrine signaling

Abstract

Dietary calcium intake modifies the action of active vitamin D [1,25(OH)₂D₃], which promotes the expression of transient receptor potential vanilloid (TRPV) 6, an epithelial calcium channel, to initiate intestinal calcium absorption in response to biological requirements. However, it is unclear whether the change caused by dietary intake results from endocrine regulation or the direct responses to luminal contents. In this study, to reveal the underlying mechanisms of intestinal calcium transport in response to dietary intake, we assessed the early postprandial responses in mice.

Although mice lacking intestinal vitamin D receptor function (Int Vdr-) exhibited severe calcium deficiency, a high-calcium diet (1 % calcium) containing 2-fold calcium compared to a control diet reversed impaired calcium absorption and compensated for the mechanisms of 1,25(OH)₂D₃-dependent transcellular calcium transport. Additionally, the calcium-sensing receptor (CaSR) was abundantly present at the basolateral site in the intestine and the signals were emphasized by a high-calcium diet.

To examine the direct response of intestinal epithelium to dietary intake, wild-type (Int Vdr+) and Int Vdr- mice were fed a control or high-calcium diet for 30- or 60-min after 23 h fasting. Serum glucose levels increased 30 min post-feeding in either genotype. TRPV6 expression increased 30 min post-feeding, whereas serum calcium levels were unaltered, suggesting that dietary intake stimulates TRPV6 expression.

These data suggest that the regulation of calcium absorption activated immediately after feeding differs from the mechanism involving endocrine responses. Factors altered in the early phase of feeding, such as glucose, may contribute to the regulation of calcium absorption.