Increased body fat mass and tissue lipotoxicity associated with ovariectomy or high-fat diet differentially affects bone and skeletal muscle metabolism in rats.

PURPOSE: The aim of this study was to evaluate and compare the musculoskeletal effects induced by ovariectomy-related fat mass deposition against the musculoskeletal effects caused by a high-fat diet. METHODS: A group of adult female rats was ovariectomized and fed a control diet. Two additional groups were sham-operated and fed a control or a high-fat diet for 19 weeks. Distal femur and serum bone parameters were measured to assess bone metabolism. Muscle protein metabolism, mitochondrial markers and triglyceride content were evaluated in tibialis anterior. Triglyceride content was evaluated in liver. Circulating inflammatory and metabolic markers were determined. RESULTS: The high-fat diet and ovariectomy led to similar increases in fat mass (+36.6-56.7%; p < 0.05) but had different impacts on bone and muscle tissues and inflammatory markers. Consumption of the high-fat diet led to decreased bone formation (-38.4%; p < 0.05), impaired muscle mitochondrial metabolism, muscle lipotoxicity and a 20.9% increase in tibialis anterior protein synthesis rate (p < 0.05). Ovariectomy was associated with higher bone turnover as bone formation increased +72.7% (p < 0.05) and bone resorption increased +76.4% (p < 0.05), leading to bone loss, a 17.9% decrease in muscle protein synthesis rate (p < 0.05) and liver lipotoxicity. CONCLUSIONS: In female rats, high-fat diet and ovariectomy triggered similar gains in fat mass but had different impacts on bone and muscle metabolism. The ovariectomy-induced mechanisms affecting the musculoskeletal system are mainly caused by estrogen depletion, which surpasses the potential-independent effect of adiposity.

Fat-soluble vitamin intestinal absorption: absorption sites in the intestine and interactions for absorption.

The interactions occurring at the intestinal level between the fat-soluble vitamins A, D, E and K (FSVs) are poorly documented. We first determined each FSV absorption profile along the duodenal-colonic axis of mouse intestine to clarify their respective absorption sites. We then investigated the interactions between FSVs during their uptake by Caco-2 cells. Our data show that vitamin A was mostly absorbed in the mouse proximal intestine, while vitamin D was absorbed in the median intestine, and vitamin E and K in the distal intestine. Significant competitive interactions for uptake were then elucidated among vitamin D, E and K, supporting the hypothesis of common absorption pathways. Vitamin A also significantly decreased the uptake of the other FSVs but, conversely, its uptake was not impaired by vitamins D and K and even promoted by vitamin E. These results should be taken into account, especially for supplement formulation, to optimise FSV absorption.

Olive oil and vitamin D synergistically prevent bone loss in mice.

As the Mediterranean diet (and particularly olive oil) has been associated with bone health, we investigated the impact of extra virgin oil as a source of polyphenols on bone metabolism. In that purpose sham-operated (SH) or ovariectomized (OVX) mice were subjected to refined or virgin olive oil. Two supplementary OVX groups were given either refined or virgin olive oil fortified with vitamin D3, to assess the possible synergistic effects with another liposoluble nutrient. After 30 days of exposure, bone mineral density and gene expression were evaluated. Consistent with previous data, ovariectomy was associated with increased bone turnover and led to impaired bone mass and micro-architecture. The expression of oxidative stress markers were enhanced as well. Virgin olive oil fortified with vitamin D3 prevented such changes in terms of both bone remodeling and bone mineral density. The expression of inflammation and oxidative stress mRNA was also lower in this group. Overall, our data suggest a protective impact of virgin olive oil as a source of polyphenols in addition to vitamin D3 on bone metabolism through improvement of oxidative stress and inflammation.

Fatty acids affect micellar properties and modulate vitamin D uptake and basolateral efflux in Caco-2 cells.

We have recently shown that vitamin D3 (cholecalciferol) absorption is not a simple passive diffusion but involves cholesterol transporters. As free fatty acids (FAs) modulate cholesterol intestinal absorption and metabolism, we hypothesized that FAs may also interact with vitamin D absorption. Effects of FAs were evaluated at different levels of cholecalciferol intestinal absorption. First, the physicochemical properties of micelles formed with different FAs were analyzed. The micelles were then administered to human Caco-2 cells in culture to evaluate FA effects on (i) cholecalciferol uptake and basolateral efflux and (ii) the regulation of genes coding proteins involved in lipid absorption process. Micellar electric charge was correlated with both FA chain length and degree of unsaturation. Long-chain FAs at 500 µM in mixed micelles decreased cholecalciferol uptake in Caco-2 cells. This decrease was annihilated as soon as the long-chain FAs were mixed with other FAs. Oleic acid significantly improved cholecalciferol basolateral efflux compared to other FAs. These results were partly explained by a modulation of genes coding for lipid transport proteins such as Niemann-pick C1-like 1 and scavenger receptor class B type I. The data reported here show for the first time that FAs can interact with cholecalciferol intestinal absorption at different key steps of the absorption process. Cholecalciferol intestinal absorption may thus be optimized according to oil FA composition.