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GPR40 mediates potential positive effects of a saturated fatty acid enriched diet on bone
Author(s) -
Philippe Claire,
Wauquier Fabien,
Landrier JeanFrançois,
Bonnet Lauriane,
MiotNoirault Elisabeth,
Rochefort Gaël Y.,
Sadoine Jérémy,
Asrih Mohamed,
Jornayvaz François R.,
Bernalier Annick,
Coxam Véronique,
Wittrant Yohann
Publication year - 2017
Publication title -
molecular nutrition and food research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.495
H-Index - 131
eISSN - 1613-4133
pISSN - 1613-4125
DOI - 10.1002/mnfr.201600219
Subject(s) - free fatty acid receptor 1 , osteoprotegerin , endocrinology , medicine , rankl , bone mineral , fatty acid , bone resorption , bone remodeling , chemistry , receptor , osteoporosis , activator (genetics) , agonist , biochemistry
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.