GPR40 mediates potential positive effects of a saturated fatty acid enriched diet on bone.

SCOPE: The stimulation of the free fatty acid receptor G-protein coupled receptor (GPR) 40 by GW9508 prevents bone loss by inhibiting osteoclast activity, both in vitro and in vivo. Here, we questioned whether the stimulation of the GPR40 receptor by dietary fatty acids may lead to the same beneficial effect on bone. METHODS AND RESULTS: We investigated (i) the impact of a fatty acid enriched diet (high-fat diet [HFD]) on bone health in C57/BL6 female mice depending on (ii) the estrogen status (ovariectomy) and (iii) the genotype (GPR40+/+ or GPR40-/- ). Bone mineral density (BMD), body composition, weight, inflammation and bone remodeling parameters were monitored. HFD decreased BMD in HFD-SH-GPR40+/+ mice but OVX failed to further impact BMD in HFD-OVX-GPR40+/+ mice, while additional bone loss was observed in HFD-OVX-GPR40-/- animals. These data suggest that when stimulated by fatty acid enriched diets GPR40 contributes to counteract ovariectomy-induced bone alteration. The sparing effect is supported by the modulation of both the osteoprotegerin/receptor activator of nuclear factor kappa-B ligand (OPG/RANKL) ratio in blood stream and the expression level of inflammatory markers in adipose tissues. Bone preservation by GPR40 stimulation is dependent on the presence of long-chain saturated fatty acids. CONCLUSION: GPR40 contributes to counter ovariectomy-induced bone loss in a context of saturated fatty acid enrichment.

Comparison of native or reformulated chicory fructans, or non-purified chicory, on rat cecal fermentation and mineral metabolism.

Chicory inulin has been identified as an effective prebiotic to promote active fermentation and lactobacilli proliferation in the large intestine, and to enhance calcium (Ca) digestive absorption and deposition in bones. The aim of this study was to compare, in a growing rat model, the effects on digestive fermentations and mineral metabolism of diets containing 7.5% inulin, using either a purified native inulin ((NAT)Inulin) or a reformulated inulin ((REF)Inulin, based on a combination of short- and long chain fructans) or dehydrated chicory. All the inulin diets elicited a marked enlargement of the cecum and acidification of the cecal contents (P < 0.01) and these diets promoted succinic acid rich fermentation together with substantial amounts of short-chain fatty acids (SCFA), especially butyrate. After 1 month of adaptation, all the inulin diets strongly enhanced Ca absorption compared to controls (P < 0.01), but this effect was no more observed after 3 months of adaptation. Magnesium (Mg) absorption was stimulated by the inulin diets after 1 and 3 months experiment. Bone parameters were significantly affected by the chicory diet (enhanced distal bone mineral density and breaking load) whereas the purified inulin diets were less effective. In conclusion, with the present model, both (NAT)Inulin and (REF)Inulin exerted similar effects as to (1) cecal fermentation and profile of end-products of bacterial metabolism, (2) stimulation of Ca and Mg digestive absorption and (3) overall effects on bone parameters. The particular effects of the chicory crude fractions on digestive fermentation and bone parameters suggest possible synergisms between inulin-type fructans and other nutrients.

Apple pectin and a polyphenol-rich apple concentrate are more effective together than separately on cecal fermentations and plasma lipids in rats.

To evaluate the effect of apple components on cecal fermentations and lipid metabolism, rats were fed diets containing 5 g/100 g apple pectin (PEC), 10 g/100 g high polyphenol freeze-dried apple (PL) or both (PEC + PL). The cecal pH was slightly acidic (6.49) only in rats fed the PEC + PL diet (controls, 7.02). The cecal short-chain fatty acid pool was enlarged by all the apple fractions, with a peak of 560 micromol in rats fed the PEC + PL diet compared with 189 micromol in controls. Butyrate concentrations were 2-fold greater in rats fed the PL diet than in controls. Substantial concentrations of galacturonate and succinate (approximately 40 mmol/L) were found in the cecum of rats fed the PEC diet and, to a lesser extent, the PEC + PL diet. The PEC + PL diet significantly lowered plasma cholesterol, whereas both the PL and PEC + PL diets lowered plasma triglycerides. Liver cholesterol and triglyceride concentrations were lower in rats fed the PEC and PEC + PL diets. Fecal bile acid excretion was markedly reduced, whereas sterol excretion was significantly increased by dietary PEC. Rats fed the PEC and PEC + PL diets also had lower apparent cholesterol absorption than controls (30 compared with 43%). In conclusion, apple pectin and the polyphenol-rich fraction were more effective when fed combined together than when fed separately on large intestine fermentations and lipid metabolism, suggesting interactions between fibers and polyphenols of apple.