High-fat diet-induced obesity augments the deleterious effects of estrogen deficiency on bone: Evidence from ovariectomized mice
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High-fat diet-induced obesity augments the deleterious effects of estrogen deficiency on bone : Evidence from ovariectomized mice. / Ali, Dalia; Figeac, Florence; Caci, Atenisa; Ditzel, Nicholas; Schmal, Clarissa; Kerckhofs, Greet; Havelund, Jesper; Færgeman, Nils; Rauch, Alexander; Tencerova, Michaela; Kassem, Moustapha.
In: Aging Cell, Vol. 21, No. 12, e13726, 2022.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - High-fat diet-induced obesity augments the deleterious effects of estrogen deficiency on bone
T2 - Evidence from ovariectomized mice
AU - Ali, Dalia
AU - Figeac, Florence
AU - Caci, Atenisa
AU - Ditzel, Nicholas
AU - Schmal, Clarissa
AU - Kerckhofs, Greet
AU - Havelund, Jesper
AU - Færgeman, Nils
AU - Rauch, Alexander
AU - Tencerova, Michaela
AU - Kassem, Moustapha
N1 - Publisher Copyright: © 2022 The Authors. Aging Cell published by Anatomical Society and John Wiley & Sons Ltd.
PY - 2022
Y1 - 2022
N2 - Several epidemiological studies have suggested that obesity complicated with insulin resistance and type 2 diabetes exerts deleterious effects on the skeleton. While obesity coexists with estrogen deficiency in postmenopausal women, their combined effects on the skeleton are poorly studied. Thus, we investigated the impact of high-fat diet (HFD) on bone and metabolism of ovariectomized (OVX) female mice (C57BL/6J). OVX or sham operated mice were fed either HFD (60%fat) or normal diet (10%fat) for 12 weeks. HFD-OVX group exhibited pronounced increase in body weight (~86% in HFD and ~122% in HFD-OVX, p < 0.0005) and impaired glucose tolerance. Bone microCT-scanning revealed a pronounced decrease in trabecular bone volume/total volume (BV/TV) (−15.6 ± 0.48% in HFD and −37.5 ± 0.235% in HFD-OVX, p < 0.005) and expansion of bone marrow adipose tissue (BMAT; +60.7 ± 9.9% in HFD vs. +79.5 ± 5.86% in HFD-OVX, p < 0.005). Mechanistically, HFD-OVX treatment led to upregulation of genes markers of senescence, bone resorption, adipogenesis, inflammation, downregulation of gene markers of bone formation and bone development. Similarly, HFD-OVX treatment resulted in significant changes in bone tissue levels of purine/pyrimidine and Glutamate metabolisms, known to play a regulatory role in bone metabolism. Obesity and estrogen deficiency exert combined deleterious effects on bone resulting in accelerated cellular senescence, expansion of BMAT and impaired bone formation leading to decreased bone mass. Our results suggest that obesity may increase bone fragility in postmenopausal women.
AB - Several epidemiological studies have suggested that obesity complicated with insulin resistance and type 2 diabetes exerts deleterious effects on the skeleton. While obesity coexists with estrogen deficiency in postmenopausal women, their combined effects on the skeleton are poorly studied. Thus, we investigated the impact of high-fat diet (HFD) on bone and metabolism of ovariectomized (OVX) female mice (C57BL/6J). OVX or sham operated mice were fed either HFD (60%fat) or normal diet (10%fat) for 12 weeks. HFD-OVX group exhibited pronounced increase in body weight (~86% in HFD and ~122% in HFD-OVX, p < 0.0005) and impaired glucose tolerance. Bone microCT-scanning revealed a pronounced decrease in trabecular bone volume/total volume (BV/TV) (−15.6 ± 0.48% in HFD and −37.5 ± 0.235% in HFD-OVX, p < 0.005) and expansion of bone marrow adipose tissue (BMAT; +60.7 ± 9.9% in HFD vs. +79.5 ± 5.86% in HFD-OVX, p < 0.005). Mechanistically, HFD-OVX treatment led to upregulation of genes markers of senescence, bone resorption, adipogenesis, inflammation, downregulation of gene markers of bone formation and bone development. Similarly, HFD-OVX treatment resulted in significant changes in bone tissue levels of purine/pyrimidine and Glutamate metabolisms, known to play a regulatory role in bone metabolism. Obesity and estrogen deficiency exert combined deleterious effects on bone resulting in accelerated cellular senescence, expansion of BMAT and impaired bone formation leading to decreased bone mass. Our results suggest that obesity may increase bone fragility in postmenopausal women.
KW - accelerated aging
KW - Aging, bone fragility
KW - bone marrow adiposity
KW - menopause
KW - obesity
KW - osteoporosis
KW - senescence
U2 - 10.1111/acel.13726
DO - 10.1111/acel.13726
M3 - Journal article
C2 - 36217558
AN - SCOPUS:85143787935
VL - 21
JO - Aging Cell
JF - Aging Cell
SN - 1474-9718
IS - 12
M1 - e13726
ER -
ID: 330390646