Enhanced bone formation in lipodystrophic PPARgamma(hyp/hyp) mice relocates haematopoiesis to the spleen.
The peroxisome proliferator-activated receptor gamma (PPARgamma) controls adipogenesis and metabolism. We demonstrate here that the absence of PPARgamma in fat has potent osteogenic activities, which affect haematopoiesis. The congenital absence of PPARgamma in fat of lipodystrophic PPARgamma(hyp/hyp) mice, strongly enhanced bone mass and consequentially reduced the bone-marrow cavity. Consistent with this, PPARgamma(hyp/hyp) mice had a significant decrease in bone marrow cellularity and resorted to extramedullary haematopoiesis in the spleen to maintain haematopoiesis. Our data indicate that antagonizing PPARgamma activity in fat could be an effective way to combat osteoporosis and suggest that haematopoietic function should be scrutinized in lipodystrophic subjects.
Cock
Terrie-Anne
TA
Institut de Génétique et de Biologie Moléculaire et Cellulaire, CNRS/INSERM/Université Louis Pasteur, 67404 Illkirch, France.
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Jonathan
J
Elefteriou
Florent
F
Karsenty
Gérard
G
Kastner
Philippe
P
Chan
Susan
S
Auwerx
Johan
J
D000818:Animals; D001842:Bone and Bones / Q000378:metabolism* / Q000473:pathology; D006411:Hematopoiesis, Extramedullary / Q000235:genetics / Q000502:physiology*; D008060:Lipodystrophy / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D047495:PPAR gamma / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D013131:Spine / Q000473:pathology; D013154:Spleen / Q000502:physiology
D047495:PPAR gamma; D012333:RNA, Messenger