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



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.



GPR40 contributes to counter ovariectomy-induced bone loss in a context of saturated fatty acid enrichment.
INRA, UMR 1019, UNH, CRNH Auvergne, Clermont-Ferrand, France.|Clermont Université, Université d'Auvergne, Unité de Nutrition Humaine, Clermont-Ferrand, France.|Equipe Alimentation, Squelette et Métabolismes, Unité de Nutrition Humaine, Centre de Recherche INRA Auvergne Rhône Alpes, Site de Theix, 63122 Saint Genés Champanelle, France.
Claire
C
Philippe
INRA, UMR 1019, UNH, CRNH Auvergne, Clermont-Ferrand, France.|Clermont Université, Université d'Auvergne, Unité de Nutrition Humaine, Clermont-Ferrand, France.|Equipe Alimentation, Squelette et Métabolismes, Unité de Nutrition Humaine, Centre de Recherche INRA Auvergne Rhône Alpes, Site de Theix, 63122 Saint Genés Champanelle, France.
Fabien
F
Wauquier
INRA, UMR1260, Nutriments Lipidiques et Prévention des Maladies Métaboliques, Marseille, France.|Faculté de Médecine, Université de la Méditerranée Aix-Marseille 1 et 2, Marseille, France.
Jean-François
JF
Landrier
INRA, UMR1260, Nutriments Lipidiques et Prévention des Maladies Métaboliques, Marseille, France.|Faculté de Médecine, Université de la Méditerranée Aix-Marseille 1 et 2, Marseille, France.
Lauriane
L
Bonnet
Clermont Université, Université d'Auvergne, Unité de Nutrition Humaine, Clermont-Ferrand, France.|INSERM, UMR990, IMTV, Clermont-Ferrand, France.
Elisabeth
E
Miot-Noirault
EA 2496 Pathologie, Imagerie et Biothérapies Orofaciales, UFR Odontologie, Université Paris Descartes and PIPA, PRES Sorbonne Paris Cité, Montrouge, France.
Gaël Y
GY
Rochefort
EA 2496 Pathologie, Imagerie et Biothérapies Orofaciales, UFR Odontologie, Université Paris Descartes and PIPA, PRES Sorbonne Paris Cité, Montrouge, France.
Jérémy
J
Sadoine
Service d'Endocrinologie, Diabétologie et Métabolisme, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland.
Mohamed
M
Asrih
Service d'Endocrinologie, Diabétologie et Métabolisme, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland.
François R
FR
Jornayvaz
INRA UR454, Unité de Microbiologie, Clermont-Ferrand, France.
Annick
A
Bernalier
INRA, UMR 1019, UNH, CRNH Auvergne, Clermont-Ferrand, France.|Clermont Université, Université d'Auvergne, Unité de Nutrition Humaine, Clermont-Ferrand, France.|Equipe Alimentation, Squelette et Métabolismes, Unité de Nutrition Humaine, Centre de Recherche INRA Auvergne Rhône Alpes, Site de Theix, 63122 Saint Genés Champanelle, France.
Véronique
V
Coxam
INRA, UMR 1019, UNH, CRNH Auvergne, Clermont-Ferrand, France.|Clermont Université, Université d'Auvergne, Unité de Nutrition Humaine, Clermont-Ferrand, France.|Equipe Alimentation, Squelette et Métabolismes, Unité de Nutrition Humaine, Centre de Recherche INRA Auvergne Rhône Alpes, Site de Theix, 63122 Saint Genés Champanelle, France.
Yohann
Y
Wittrant
D000818:Animals; D015519:Bone Density / Q000187:drug effects; D059305:Diet, High-Fat / Q000009:adverse effects*; D004195:Disease Models, Animal; D005227:Fatty Acids / Q000494:pharmacology*; D005260:Female; D008744:Methylamines / Q000494:pharmacology; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D010024:Osteoporosis / Q000178:diet therapy* / Q000209:etiology / Q000517:prevention & control; D010052:Ovariectomy / Q000009:adverse effects; D015434:Panniculitis / Q000209:etiology / Q000473:pathology; D011422:Propionates / Q000494:pharmacology; D053245:RANK Ligand / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled / Q000235:genetics / Q000378:metabolism*
D005227:Fatty Acids; C473036:Ffar1 protein, mouse; C515630:GW9508; D008744:Methylamines; D011422:Propionates; D053245:RANK Ligand; D043562:Receptors, G-Protein-Coupled; C505689:Tnfsf11 protein, mouse
Free fatty acid receptor; GPR40; High-fat diet; Nutrition; Osteoporosis