Bone marrow lipids in normal and anemic mice

Potter, Jane E.R.; Wright, Esmond

doi:10.1002/ajh.2830080404

Cited by 7 publications

(3 citation statements)

References 26 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In addition to an absence of bone marrow adipocytes, the kit receptor-deficient kit W/W-v mice have multiple abnormalities in fat metabolism. These abnormalities include hypertriglyceridemia and hypercholesterolemia [44, 45]. Chylomicrons, very low density lipoprotein, and intermediate density lipoprotein are also reported to be elevated.…”

Section: Discussionmentioning

confidence: 99%

Failure to generate bone marrow adipocytes does not protect mice from ovariectomy-induced osteopenia

Iwaniec

Turner

2013

Bone

View full text Add to dashboard Cite

A reciprocal association between bone marrow fat and bone mass has been reported in ovariectomized rodents, suggesting that bone marrow adipogenesis has a negative effect on bone growth and turnover balance. Mice with loss of function mutations in kit receptor (kitW/W-v) have no bone marrow adipocytes in tibia or lumbar vertebra. We therefore tested the hypothesis that marrow fat contributes to development of osteopenia by comparing the skeletal response to ovariectomy (ovx) in growing wild type (WT) and bone marrow adipocyte-deficient kitW/W-v mice. Mice were ovx at 4 weeks of age and sacrificed 4 or 10 weeks post-surgery. Body composition was measured at necropsy by dual-energy X-ray absorptiometry. Cortical (tibia) and cancellous (tibia and lumbar vertebra) bone architecture were evaluated by microcomputed tomography. Bone marrow adipocyte size and density, osteoblast- and osteoclast-lined bone perimeters, and bone formation were determined by histomorphometry. Ovx resulted in an increase in total body fat mass at 10 weeks post-ovx in both genotypes, but the response was attenuated in the in kitW/W-v mice. Adipocytes were present in bone marrow of tibia and lumbar vertebra in WT mice and bone marrow adiposity increased following ovx. In contrast, marrow adipocytes were not detected in either intact or ovx kitW/W-v mice. However, ovx in WT and kitW/W-v mice resulted in statistically indistinguishable changes in cortical and cancellous bone mass, cortical and cancellous bone formation rate, and cancellous osteoblast and osteoclast-lined bone perimeters. In conclusion, our findings do not support a causal role for increased bone marrow fat as a mediator of ovx-induced osteopenia in mice.

show abstract

Section: Discussionmentioning

confidence: 99%

Failure to generate bone marrow adipocytes does not protect mice from ovariectomy-induced osteopenia

Iwaniec

Turner

2013

Bone

View full text Add to dashboard Cite

show abstract

“…The receptor tyrosine kinase cKit is required for fat storage in long bones and lumbar vertebra of mice ( 47 , 48 ). Therefore, attenuation of cKit signaling provides a novel approach for investigating the regulation and function of BMAT.…”

Section: Discussionmentioning

confidence: 99%

Leptin and environmental temperature as determinants of bone marrow adiposity in female mice

et al. 2022

View full text Add to dashboard Cite

Bone marrow adipose tissue (BMAT) levels are higher in distal femur metaphysis of female mice housed at thermoneutral (32°C) than in mice housed at 22°C, as are abdominal white adipose tissue (WAT) mass, and serum leptin levels. We performed two experiments to explore the role of increased leptin in temperature-enhanced accrual of BMAT. First, we supplemented 6-week-old female C57BL/6J (B6) mice with leptin for 2 weeks at 10 µg/d using a subcutaneously implanted osmotic pump. Controls consisted of ad libitum (ad lib) fed mice and mice pair fed to match food intake of leptin-supplemented mice. The mice were maintained at 32°C for the duration of treatment. At necropsy, serum leptin in leptin-supplemented mice did not differ from ad lib mice, suggesting suppression of endogenous leptin production. In support, Ucp1 expression in BAT, percent body fat, and abdominal WAT mass were lower in leptin-supplemented mice. Leptin-supplemented mice also had lower BMAT and higher bone formation in distal femur metaphysis compared to the ad lib group, changes not replicated by pair-feeding. In the second experiment, BMAT response was evaluated in 6-week-old female B6 wild type (WT), leptin-deficient ob/ob and leptin-treated (0.3 μg/d) ob/ob mice housed at 32°C for the 2-week duration of the treatment. Compared to mice sacrificed at baseline (22°C), BMAT increased in ob/ob mice as well as WT mice, indicating a leptin independent response to increased temperature. However, infusion of ob/ob mice with leptin, at a dose rate having negligible effects on either energy metabolism or serum leptin levels, attenuated the increase in BMAT. In summary, increased housing temperature and increased leptin have independent but opposing effects on BMAT in mice.

show abstract

“…Sublethal models which do not require hematopoietic rescue have also been developed with 5fluorouracil or cytarabine treatments (194,236). Both radiation and chemotherapeutic treatments induce dramatic increases in BMAT also in patients (234,244), whereas certain disorders of inefficient hematopoiesis (e.g., W/Wv mice) are associated with greatly reduced BMAT and a modified lipid composition of the stroma (245,246). The biological implications of BMAT in neoplastic progression within the BM microenvironment are only beginning to unravel (247)(248)(249)(250)(251).…”

Section: Pharmacological Modulationmentioning

confidence: 99%

Reporting Guidelines, Review of Methodological Standards, and Challenges Toward Harmonization in Bone Marrow Adiposity Research. Report of the Methodologies Working Group of the International Bone Marrow Adiposity Society

et al. 2020

View full text Add to dashboard Cite

The interest in bone marrow adiposity (BMA) has increased over the last decade due to its association with, and potential role, in a range of diseases (osteoporosis, diabetes, anorexia, cancer) as well as treatments (corticosteroid, radiation, chemotherapy, thiazolidinediones). However, to advance the field of BMA research, standardization of methods is desirable to increase comparability of study outcomes and foster collaboration. Therefore, at the 2017 annual BMA meeting, the International Bone Marrow Adiposity Society (BMAS) founded a working group to evaluate methodologies in BMA research. All BMAS members could volunteer to participate. The working group members, who are all active preclinical or clinical BMA researchers, searched the literature for articles investigating BMA and discussed the results during personal and telephone conferences. According to the consensus opinion, both based on the review of the literature and on expert opinion, we describe existing methodologies and discuss the challenges and future directions for (1) histomorphometry of bone marrow adipocytes, (2) ex vivo BMA imaging, (3) in vivo BMA imaging, (4) cell isolation, culture, differentiation and in vitro modulation of primary bone marrow adipocytes and bone marrow stromal cell precursors, (5) lineage tracing and in vivo BMA modulation, and (6) BMA biobanking. We identify as accepted standards in BMA research: manual histomorphometry and osmium tetroxide 3D contrast-enhanced µCT for ex vivo quantification, specific MRI sequences (WFI and H-MRS) for in vivo studies, and RT-qPCR with a minimal four gene panel or lipid-based assays for in vitro quantification of bone marrow adipogenesis. Emerging techniques are described which may soon come to complement or substitute these gold standards. Known confounding factors and minimal reporting standards are presented, and their use is encouraged to facilitate comparison across studies. In conclusion, specific BMA methodologies have been developed. However, important challenges remain. In particular, we advocate for the harmonization of methodologies, the precise reporting of known confounding factors, and the identification of methods to modulate BMA independently from other tissues. Wider use of existing animal models with impaired BMA production (e.g., Pfrt −/− , Kit W/W−v) and development of specific BMA deletion models would be highly desirable for this purpose.

show abstract

Bone marrow lipids in normal and anemic mice

Cited by 7 publications

References 26 publications

Failure to generate bone marrow adipocytes does not protect mice from ovariectomy-induced osteopenia

Failure to generate bone marrow adipocytes does not protect mice from ovariectomy-induced osteopenia

Leptin and environmental temperature as determinants of bone marrow adiposity in female mice

Reporting Guidelines, Review of Methodological Standards, and Challenges Toward Harmonization in Bone Marrow Adiposity Research. Report of the Methodologies Working Group of the International Bone Marrow Adiposity Society

Contact Info

Product

Resources

About