Apolipoprotein E-dependent inverse regulation of vertebral bone and adipose tissue mass in C57Bl/6 mice: modulation by diet-induced obesity.
The long prevailing view that obesity is generally associated with beneficial effects on the skeleton has recently been challenged. Apolipoprotein E (apoE) is known to influence both adipose tissue and bone. The goal of the current study was to examine the impact of apoE on the development of fat mass and bone mass in mice under conditions of diet-induced obesity (DIO). Four week-old male C57BL/6 (WT) and apoE-deficient (apoE(-/-)) mice received a control or a diabetogenic high-fat diet (HFD) for 16 weeks. The control-fed apoE(-/-) animals displayed less total fat mass and higher lumbar trabecular bone volume (BV/TV) than WT controls. When stressed with HFD to induce obesity, apoE(-/-) mice had a lower body weight, lower serum glucose, insulin and leptin levels and accumulated less white adipose tissue mass at all sites including bone marrow. While WT animals showed no significant change in BV/TV and bone formation rate (BFR), apoE deficiency led to a decrease of BV/TV and BFR when stressed with HFD. Bone resorption parameters were not affected by HFD in either genotype. Taken together, under normal dietary conditions, apoE-deficient mice acquire less fat mass and more bone mass than WT littermates. When stressed with HFD to develop DIO, the difference of total body fat mass becomes larger and the difference of bone mass smaller between the genotypes. We conclude that apoE is involved in an inverse regulation of bone mass and fat mass in growing mice and that this effect is modulated by diet-induced obesity.
Bartelt
Alexander
A
Department of Biochemistry and Molecular Biology II: Molecular Cell Biology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany. abartelt@uke.uni-hamburg.de
Beil
F Timo
FT
Schinke
Thorsten
T
Roeser
Kerstin
K
Ruether
Wolfgang
W
Heeren
Joerg
J
Niemeier
Andreas
A
D017667:Adipocytes / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D000273:Adipose Tissue / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D000818:Animals; D001057:Apolipoproteins E / Q000172:deficiency / Q000378:metabolism*; D001786:Blood Glucose / Q000378:metabolism; D001854:Bone Marrow Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D016723:Bone Remodeling / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D004032:Diet; D004041:Dietary Fats / Q000008:administration & dosage / Q000494:pharmacology; D004822:Epididymis / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D007328:Insulin / Q000378:metabolism; D020738:Leptin / Q000097:blood; D008055:Lipids / Q000097:blood; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009765:Obesity / Q000097:blood / Q000378:metabolism* / Q000473:pathology* / Q000503:physiopathology; D009929:Organ Size / Q000187:drug effects; D013131:Spine / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D040521:Subcutaneous Tissue / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D014781:Viscera / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D015430:Weight Gain / Q000187:drug effects
D001057:Apolipoproteins E; D001786:Blood Glucose; D004041:Dietary Fats; D007328:Insulin; D020738:Leptin; D008055:Lipids