Effects of high fat feeding and dietary vitamin D on calcium, bone, and vitamin D metabolism in mature mice

Dietary fat sources containing high caloric energy are closely linked to energy overconsumption induced obesity leading to a variety of health problems, including compromised bone quality. High fat diets (HFD) also affect calcium metabolism. However, effects of HFD on intestinal calcium absorption and bone health in mature animals have not been addressed, and different types of dietary fatty acids may have differential effects (e.g. monounsaturated fatty acids (MUFA) vs. saturated fatty acids (SFA). In addition, low circulating vitamin D status is commonly found in obese individuals. However, the nature of the association between vitamin D deficiency and obesity remains unclear because an underlying mechanism for the association has not been delineated. Therefore, in the current dissertation, we sought to reveal the effects of dietary fat and vitamin D intake on calcium and vitamin D metabolism and bone health using a mature mouse model. In study 1, the effects of HFD enriched with MUFA or with SFA on intestinal calcium absorption and bone health in mature lean mice were investigated. C57BL/6J mice were weight-controlled fed with either 10% normal fat diet (NFD) or a HFD (45% fat) enriched with either MUFA or SFA for 10wk. We found that high compared with normal fat intake induced higher fractional Ca absorption (Ca45 isotope method) and this did not differ with the type of dietary fatty acids (MUFA vs. SFA). In contrast, only the high fat feeding with SFA adversely affected total and femoral area bone mineral density (dual-energy X-ray absorptiometry), while MUFA was associated with greater femoral trabecular bone volume fraction (BV/TV) and thickness (micro-computerized tomography system). In study 2, the objective was to determine whether high MUFA intake would have a neutral or even a beneficial effect on mature bone health under conditions of excess caloric intake and obesity, and whether high MUFA and SFA feeding would differentially affect vitamin D metabolism in obese mice. After ad libitum feeding C57BL/6J mice 10% NFD or 45% HFD enriched with MUFA or SFA for 10wk, we found that the HFD enriched with SFA, but not MUFA, resulted in greater energy intake, weight gain, total body fat mass (EchoMRI Body Composition Analyzer), and liver fat. High SFA intake, but not MUFA, also adversely affected femoral trabecular bone parameters, though no detrimental effects of SFA on bone mass were seen in mature mice under the condition of excess caloric intake and obesity. Moreover, high fat feeding lowered circulating 25OHD concentration (ELISA), which was also inversely associated with body fat percentage. However, this finding was not explained by differential effects of MUFA and SFA on gene (rt-PCR) and protein (western blotting) expression of hepatic vitamin D 25-hydroxylase Cyp2r1 in mature mice. In study 3, the aim was to determine effects of dietary vitamin D on food intake and adiposity with and without high fat feeding. We found that supplemental vitamin D showed no beneficial effects on preventing HFD-induced obesity. Under conditions of high fat feeding, low vitamin D intake appeared to increase food intake, weight gain, and adiposity compared to the HFD-normal vitamin D diet, but the magnitude of the effect was inconsistent between two separate experiments. We also investigated the role of low vitamin D intake on serotonin production and major markers involved in the vitamin D and serotonergic pathways in the brain. It was found that low D intake, regardless of the presence of high fat feeding, lowered gene expression of vitamin D 1α-hydroxylase Cyp27b1 and frontal cortex serotonin concentrations in the brain. In conclusion, this dissertation addressed the role of different amounts (high vs. normal) and types (MUFA vs. SFA) of dietary fat intake on Ca and vitamin D metabolism and bone health in mature female mice. Our findings support that high fat feeding increases intestinal Ca absorption and lowers circulating vitamin D status, and these effects were not dependent on the type of dietary fatty acids (MUFA vs. SFA). In contrast, dietary fat rich in SFA has detrimental effects on mature bone quality regardless of the presence of obesity, whereas high MUFA intake shows a neutral effect. Moreover, it was found that vitamin D deficiency combined with HFD potentially promotes food intake and weight gain that might be related to lowered cerebral serotonin concentration. Overall, the interaction of fatty acids on calcium and vitamin D metabolism and bone health is complex and deserves further attention in future studies.Ph.D.Includes bibliographical referencesby Yang Wan