The effect of PPARγ inhibition on bone marrow adipose tissue and bone in C3H/HeJ mice

Kerensa M. Beekman, Annegreet G. Veldhuis-Vlug, Albert van der Veen, Martin den Heijer, Mario Maas, Greet Kerckhofs, Tatjana N. Parac-Vogt, Peter H. Bisschop, Nathalie Bravenboer

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

Bone marrow adipose tissue (BMAT) increases after menopause, and increased BMAT is associated with osteoporosis and prevalent vertebral fractures. Peroxisome proliferator-activated receptor-γ (PPARγ) activation promotes adipogenesis and inhibits osteoblastogenesis; therefore, PPARγ is a potential contributor to the postmenopausal increase in BMAT and decrease in bone mass. The aim of this study is to determine if PPARγ inhibition can prevent ovariectomy-induced BMAT increase and bone loss in C3H/HeJ mice. Fourteen-week-old female C3H/HeJ mice (n = 40) were allocated to four intervention groups: sham surgery (Sham) or ovariectomy (OVX; isoflurane anesthesia) with either vehicle (Veh) or PPARγ antagonist administration (GW9662; 1 mg·kg -1 ·day -1 , daily intraperitoneal injections) for 3 wk. We measured BMAT volume, adipocyte size, adipocyte number. and bone structural parameters in the proximal metaphysis of the tibia using polyoxometa-late-based contrast enhanced-nanocomputed topogaphy. Bone turnover was measured in the contralateral tibia using histomorphometry. The effects of surgery and treatment were analyzed by two-way ANOVA. OVX increased the BMAT volume fraction (Sham + Veh: 2.9 ± 2.7% vs. OVX + Veh: 8.1 ± 5.0%: P < 0.001), average adipocyte diameter (Sham + Veh: 19.3 ± 2.6 μm vs. OVX + Veh: 23.1 ± 3.4 μm: P = 0.001), and adipocyte number (Sham + Veh: 584 ± 337cells/μm 3 vs. OVX + Veh: 824 ± 113cells/μm 3 : P = 0.03), while OVX decreased bone volume fraction (Sham + Veh: 15.5 ± 2.8% vs. OVX + Veh: 7.7 ± 1.9%; P < 0.001). GW9662 had no effect on BMAT, bone structural parameters, or bone turnover. In conclusion, ovariectomy increased BMAT and decreased bone volume in C3H/HeJ mice. The PPARγ antagonist GW9662 had no effect on BMAT or bone volume in C3H/HeJ mice, suggesting that BMAT accumulation is regulated independently of PPARγ in C3H/HeJ mice.

Original languageEnglish
Pages (from-to)E96-E105
JournalAmerican Journal of Physiology - Endocrinology and Metabolism
Volume316
Issue number1
DOIs
Publication statusPublished - 1 Jan 2019

Cite this

@article{177b99e8d43d465abf93d755ead6d38f,
title = "The effect of PPARγ inhibition on bone marrow adipose tissue and bone in C3H/HeJ mice",
abstract = "Bone marrow adipose tissue (BMAT) increases after menopause, and increased BMAT is associated with osteoporosis and prevalent vertebral fractures. Peroxisome proliferator-activated receptor-γ (PPARγ) activation promotes adipogenesis and inhibits osteoblastogenesis; therefore, PPARγ is a potential contributor to the postmenopausal increase in BMAT and decrease in bone mass. The aim of this study is to determine if PPARγ inhibition can prevent ovariectomy-induced BMAT increase and bone loss in C3H/HeJ mice. Fourteen-week-old female C3H/HeJ mice (n = 40) were allocated to four intervention groups: sham surgery (Sham) or ovariectomy (OVX; isoflurane anesthesia) with either vehicle (Veh) or PPARγ antagonist administration (GW9662; 1 mg·kg -1 ·day -1 , daily intraperitoneal injections) for 3 wk. We measured BMAT volume, adipocyte size, adipocyte number. and bone structural parameters in the proximal metaphysis of the tibia using polyoxometa-late-based contrast enhanced-nanocomputed topogaphy. Bone turnover was measured in the contralateral tibia using histomorphometry. The effects of surgery and treatment were analyzed by two-way ANOVA. OVX increased the BMAT volume fraction (Sham + Veh: 2.9 ± 2.7{\%} vs. OVX + Veh: 8.1 ± 5.0{\%}: P < 0.001), average adipocyte diameter (Sham + Veh: 19.3 ± 2.6 μm vs. OVX + Veh: 23.1 ± 3.4 μm: P = 0.001), and adipocyte number (Sham + Veh: 584 ± 337cells/μm 3 vs. OVX + Veh: 824 ± 113cells/μm 3 : P = 0.03), while OVX decreased bone volume fraction (Sham + Veh: 15.5 ± 2.8{\%} vs. OVX + Veh: 7.7 ± 1.9{\%}; P < 0.001). GW9662 had no effect on BMAT, bone structural parameters, or bone turnover. In conclusion, ovariectomy increased BMAT and decreased bone volume in C3H/HeJ mice. The PPARγ antagonist GW9662 had no effect on BMAT or bone volume in C3H/HeJ mice, suggesting that BMAT accumulation is regulated independently of PPARγ in C3H/HeJ mice.",
keywords = "C3H/HeJ mice, PPAR gamma antagonist, bone marrow adipose tissue, bone turnover, ovariectomy",
author = "Beekman, {Kerensa M.} and Veldhuis-Vlug, {Annegreet G.} and {van der Veen}, Albert and {den Heijer}, Martin and Mario Maas and Greet Kerckhofs and Parac-Vogt, {Tatjana N.} and Bisschop, {Peter H.} and Nathalie Bravenboer",
year = "2019",
month = "1",
day = "1",
doi = "10.1152/ajpendo.00265.2018",
language = "English",
volume = "316",
pages = "E96--E105",
journal = "American Journal of Physiology - Endocrinology and Metabolism",
issn = "0193-1849",
publisher = "American Physiological Society",
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The effect of PPARγ inhibition on bone marrow adipose tissue and bone in C3H/HeJ mice. / Beekman, Kerensa M.; Veldhuis-Vlug, Annegreet G.; van der Veen, Albert; den Heijer, Martin; Maas, Mario; Kerckhofs, Greet; Parac-Vogt, Tatjana N.; Bisschop, Peter H.; Bravenboer, Nathalie.

In: American Journal of Physiology - Endocrinology and Metabolism, Vol. 316, No. 1, 01.01.2019, p. E96-E105.

Research output: Contribution to journalArticleAcademicpeer-review

TY - JOUR

T1 - The effect of PPARγ inhibition on bone marrow adipose tissue and bone in C3H/HeJ mice

AU - Beekman, Kerensa M.

AU - Veldhuis-Vlug, Annegreet G.

AU - van der Veen, Albert

AU - den Heijer, Martin

AU - Maas, Mario

AU - Kerckhofs, Greet

AU - Parac-Vogt, Tatjana N.

AU - Bisschop, Peter H.

AU - Bravenboer, Nathalie

PY - 2019/1/1

Y1 - 2019/1/1

N2 - Bone marrow adipose tissue (BMAT) increases after menopause, and increased BMAT is associated with osteoporosis and prevalent vertebral fractures. Peroxisome proliferator-activated receptor-γ (PPARγ) activation promotes adipogenesis and inhibits osteoblastogenesis; therefore, PPARγ is a potential contributor to the postmenopausal increase in BMAT and decrease in bone mass. The aim of this study is to determine if PPARγ inhibition can prevent ovariectomy-induced BMAT increase and bone loss in C3H/HeJ mice. Fourteen-week-old female C3H/HeJ mice (n = 40) were allocated to four intervention groups: sham surgery (Sham) or ovariectomy (OVX; isoflurane anesthesia) with either vehicle (Veh) or PPARγ antagonist administration (GW9662; 1 mg·kg -1 ·day -1 , daily intraperitoneal injections) for 3 wk. We measured BMAT volume, adipocyte size, adipocyte number. and bone structural parameters in the proximal metaphysis of the tibia using polyoxometa-late-based contrast enhanced-nanocomputed topogaphy. Bone turnover was measured in the contralateral tibia using histomorphometry. The effects of surgery and treatment were analyzed by two-way ANOVA. OVX increased the BMAT volume fraction (Sham + Veh: 2.9 ± 2.7% vs. OVX + Veh: 8.1 ± 5.0%: P < 0.001), average adipocyte diameter (Sham + Veh: 19.3 ± 2.6 μm vs. OVX + Veh: 23.1 ± 3.4 μm: P = 0.001), and adipocyte number (Sham + Veh: 584 ± 337cells/μm 3 vs. OVX + Veh: 824 ± 113cells/μm 3 : P = 0.03), while OVX decreased bone volume fraction (Sham + Veh: 15.5 ± 2.8% vs. OVX + Veh: 7.7 ± 1.9%; P < 0.001). GW9662 had no effect on BMAT, bone structural parameters, or bone turnover. In conclusion, ovariectomy increased BMAT and decreased bone volume in C3H/HeJ mice. The PPARγ antagonist GW9662 had no effect on BMAT or bone volume in C3H/HeJ mice, suggesting that BMAT accumulation is regulated independently of PPARγ in C3H/HeJ mice.

AB - Bone marrow adipose tissue (BMAT) increases after menopause, and increased BMAT is associated with osteoporosis and prevalent vertebral fractures. Peroxisome proliferator-activated receptor-γ (PPARγ) activation promotes adipogenesis and inhibits osteoblastogenesis; therefore, PPARγ is a potential contributor to the postmenopausal increase in BMAT and decrease in bone mass. The aim of this study is to determine if PPARγ inhibition can prevent ovariectomy-induced BMAT increase and bone loss in C3H/HeJ mice. Fourteen-week-old female C3H/HeJ mice (n = 40) were allocated to four intervention groups: sham surgery (Sham) or ovariectomy (OVX; isoflurane anesthesia) with either vehicle (Veh) or PPARγ antagonist administration (GW9662; 1 mg·kg -1 ·day -1 , daily intraperitoneal injections) for 3 wk. We measured BMAT volume, adipocyte size, adipocyte number. and bone structural parameters in the proximal metaphysis of the tibia using polyoxometa-late-based contrast enhanced-nanocomputed topogaphy. Bone turnover was measured in the contralateral tibia using histomorphometry. The effects of surgery and treatment were analyzed by two-way ANOVA. OVX increased the BMAT volume fraction (Sham + Veh: 2.9 ± 2.7% vs. OVX + Veh: 8.1 ± 5.0%: P < 0.001), average adipocyte diameter (Sham + Veh: 19.3 ± 2.6 μm vs. OVX + Veh: 23.1 ± 3.4 μm: P = 0.001), and adipocyte number (Sham + Veh: 584 ± 337cells/μm 3 vs. OVX + Veh: 824 ± 113cells/μm 3 : P = 0.03), while OVX decreased bone volume fraction (Sham + Veh: 15.5 ± 2.8% vs. OVX + Veh: 7.7 ± 1.9%; P < 0.001). GW9662 had no effect on BMAT, bone structural parameters, or bone turnover. In conclusion, ovariectomy increased BMAT and decreased bone volume in C3H/HeJ mice. The PPARγ antagonist GW9662 had no effect on BMAT or bone volume in C3H/HeJ mice, suggesting that BMAT accumulation is regulated independently of PPARγ in C3H/HeJ mice.

KW - C3H/HeJ mice

KW - PPAR gamma antagonist

KW - bone marrow adipose tissue

KW - bone turnover

KW - ovariectomy

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U2 - 10.1152/ajpendo.00265.2018

DO - 10.1152/ajpendo.00265.2018

M3 - Article

VL - 316

SP - E96-E105

JO - American Journal of Physiology - Endocrinology and Metabolism

JF - American Journal of Physiology - Endocrinology and Metabolism

SN - 0193-1849

IS - 1

ER -