Upregulation of Hepatic 11β-Hydroxysteroid Dehydrogenase-1 Expression in Calcium-Deficient Rats

Abstract

Background: Many epidemiologic studies have reported a link between calcium (Ca) deficiency and metabolic syndrome. In this study, we examine Ca deficiency in rats and whether changes in glucocorticoid metabolism are induced. Methods: Twelve-week-old female Wistar rats were weaned onto a very-low-Ca diet (low-Ca group) or a control diet (control group) for 2 weeks. Quantitative real-time PCR was used to assess mRNA for 11β-hydroxysteroid dehydrogenase-1 (11β-HSD1), 11β-HSD2, phosphoenolpyruvate carboxykinase, peroxisome proliferator-activated receptor-α, and glucocorticoid receptor in the liver. Concentrations of adiponectin, leptin, corticosterone, intact parathyroid hormone, asymmetrical dimethylarginine and insulin in fasting serum were determined using a rat-specific enzyme-linked immunosorbent assay. Glucose concentrations were measured using a glucose oxidase system. Serum ionized Ca levels were measured with an automatic ion-selective electrode analyzer. Serum nitrite/nitrate levels were measured using a colorimetric assay kit. Results: After 2 weeks, no differences in serum glucose, corticosterone or insulin levels were observed. The low-Ca group rats showed higher homeostasis model assessment insulin resistance, lower adiponectin and higher intact parathyroid hormone levels. Serum nitrite/nitrate and asymmetrical dimethylarginine were significantly higher in the low-Ca group than in the control group. The expression of hepatic 11β-HSD1 mRNA was upregulated, while hepatic phosphoenolpyruvate carboxykinase expression was downregulated in the low-Ca group. Glucocorticoid receptor, peroxisome proliferator-activated receptor-α and 11β-HSD2 expression levels showed a similar tendency. Conclusion: A low-Ca diet alters glucocorticoid metabolism, which leads to hepatic upregulation of 11β-HSD1, and is possibly a key mechanism inducing the metabolic complications of Ca deficiency.

A Calcium-Deficient Diet in Rat Dams during Gestation and Nursing Affects Hepatic 11β-hydroxysteroid dehydrogenase-1 Expression in the Offspring

“…We previously reported that Hsd11b1 expression in the liver increases in response to a Ca-deficient diet in adult rats for 2 wk [23]. In our current study, however, the expression of Hsd11b1 mRNA in male offspring (DD) from Ca-deficient dams was lower than that in male offspring (CC) from control dams.…”

“…We previously reported that a low Ca diet alters glucocorticoid metabolism, leading to hepatic up-regulation of Hsd11b1 in rats [23]. We also reported that feeding a Ca-restricted diet to pregnant rats results in hypomethylation and decreased expression from the Hsd11b1 promoter in the liver of offspring at day 21 [24].…”

A calcium-deficient diet in pregnant, nursing rats induces hypomethylation of specific cytosines in the 11β-hydroxysteroid dehydrogenase-1 promoter in pup liver

“…Genomic methylation is considered an epigenetic mechanism important for developmental programming, an area that is currently of high interest to nutrionists and other basic scientists. Many dietary and nutritional interventions have a significant impact on biological functions and disease susceptibilities via alterations to epigenetic programming [10][11][12]22,31]. Nutrition, among many other environmental factors, is a key player that can induce epigenetic changes not only in the directly exposed organisms but also in subsequent generations because of transgenerational inheritance of epigenetic modifications.…”

“…Calcium deficiency in the early post-weaning stage is associated with a reduction in adiponectin release from isolated rat mesenteric adipocytes [21]. We recently reported that a low-Ca diet alters glucocorticoid metabolism, which in turn leads to up-regulation of Hsd11b1 in rat liver tissues [22].…”

A Calcium-Deficient Diet in Rat Dams during Gestation Decreases HOMA-β% in 3 Generations of Offspring

“…Calcium (Ca) plays an important role in the pathogenesis of insulin resistance and obesity, suggesting that hypocalcemia is a risk factor for developing these conditions [1,2,3]. Several reports have shown an inverse relationship between Ca intake and body fat mass [2,4,5,6].…”