Marrow Adipose Tissue Expansion Coincides with Insulin Resistance in MAGP1-Deficient Mice

Walji, Tezin A.; Turecamo, Sarah; Sanchez, Alejandro Coca; Anthony, Bryan A.; Abou-Ezzi, Grazia; Scheller, Erica L.; Link, Daniel C.; Mecham, Robert P.; Craft, Clarissa S.

doi:10.3389/fendo.2016.00087

Cited by 17 publications

(29 citation statements)

References 31 publications

(44 reference statements)

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“…Insulin resistance is associated with higher circulating free fatty acids and triglyceride storage in ectopic sites such as the liver and muscle. In a mouse model of insulin resistance, marrow fat expansion occurred concurrently with insulin resistance . Animal models of both type 1 and type 2 diabetes have demonstrated increased marrow fat and bone mass loss compared with controls .…”

Section: Discussionmentioning

confidence: 99%

“…In a mouse model of insulin resistance, marrow fat expansion occurred concurrently with insulin resistance. (47) Animal models of both type 1 and type 2 diabetes have demonstrated increased marrow fat and bone mass loss compared with controls. (22,23,48) In humans, marrow fat differences with diabetes are less clear, (32,43,49,50) although in one recent study of morbidly obese adults, participants with type 2 diabetes had higher amounts of marrow fat than nondiabetics.…”

Section: Discussionmentioning

confidence: 99%

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Bone Marrow Fat Changes After Gastric Bypass Surgery Are Associated With Loss of Bone Mass

Kim

Schwartz

et al. 2017

Journal of Bone and Mineral Research

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Bone marrow fat is a unique fat depot that may regulate bone metabolism. Marrow fat is increased in states of low bone mass, severe underweight, and diabetes. However, longitudinal effects of weight loss and improved glucose homeostasis on marrow fat are unclear, as is the relationship between marrow fat and BMD changes. We hypothesized that after Roux-en-Y gastric bypass (RYGB) surgery, marrow fat changes are associated with BMD loss. We enrolled 30 obese women, stratified by diabetes status. Before and 6 months after RYGB, we measured BMD by DXA and QCT and vertebral marrow fat content by magnetic resonance spectroscopy. At baseline, those with higher marrow fat had lower BMD. Postoperatively, total body fat declined dramatically in all participants. Effects of RYGB on marrow fat differed by diabetes status (p=0.03). Nondiabetic women showed no significant mean change in marrow fat (+1.8%, 95% CI −1.8% to +5.4%, p=0.29), although those who lost more total body fat were more likely to have marrow fat increases (r=−0.70, p=0.01). In contrast, diabetic women demonstrated a mean marrow fat change of −6.5% (95% CI −13.1% to 0%, p=0.05). Overall, those with greater improvements in hemoglobin A1c had decreases in marrow fat (r=0.50, p=0.01). Increases in IGF-1, a potential mediator of the marrow fat-bone relationship, were associated with marrow fat declines (r=−0.40, p=0.05). Spinal volumetric BMD decreased by 6.4% ±5.9% (p<0.01), and femoral neck areal BMD decreased by 4.3% ±4.1% (p<0.01). Marrow fat and BMD changes were negatively associated, such that those with marrow fat increases had more BMD loss at both spine (r=−0.58, p<0.01) and femoral neck (r=−0.49, p=0.01), independent of age and menopause. Our findings suggest that glucose metabolism and weight loss may influence marrow fat behavior, and marrow fat may be a determinant of bone metabolism.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Bone Marrow Fat Changes After Gastric Bypass Surgery Are Associated With Loss of Bone Mass

Kim

Schwartz

et al. 2017

Journal of Bone and Mineral Research

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“…Bone, hematopoietic cells, and BMAT are contained within a closed system, and thus expansion of one of these populations is often at the expense of one or both of the others. Although this reciprocal relationship undoubtedly holds true at the extremes, regulated changes in extracellular fluid volume and cell size may act to buffer the tightness of this ‘zero-sum’ relationship 57 .…”

Section: Functional Interactions Between Bma and Other Cells Within Tmentioning

confidence: 99%

Development, regulation, metabolism and function of bone marrow adipose tissues

Hardij

Bagchi

et al. 2018

Bone

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119

128

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Most adipocytes exist in discrete depots throughout the body, notably in well-defined white and brown adipose tissues. However, adipocytes also reside within specialized niches, of which the most abundant is within bone marrow. Whereas bone marrow adipose tissue (BMAT) shares many properties in common with white adipose tissue, the distinct functions of BMAT are reflected by its development, regulation, protein secretion, and lipid composition. In addition to its potential role as a local energy reservoir, BMAT also secretes proteins, including adiponectin, RANK ligand, dipeptidyl peptidase-4, and stem cell factor, which contribute to local marrow niche functions and which may also influence global metabolism. The characteristics of BMAT are also distinct depending on whether marrow adipocytes are contained within yellow or red marrow, as these can be thought of as 'constitutive' and 'regulated', respectively. The rBMAT for instance can be expanded or depleted by myriad factors, including age, nutrition, endocrine status and pharmaceuticals. Herein we review the site specificity, age-related development, regulation and metabolic characteristics of BMAT under various metabolic conditions, including the functional interactions with bone and hematopoietic cells.

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“…In contrast to visceral WAT, pro-inflammatory gene expression was decreased while the expression of genes of the insulin signaling pathway increased in BMAT of HFD-fed mice, suggesting a differential metabolic regulation of BMAT adipocytes (161). Walji et al (213) used microfibril-associated glycoprotein-1 (MAGP1) deficient (Mfap2 −/− ) mice that develop adult-onset obesity that precedes insulin resistance. In these mice, BMAT increased relative to WT mice coincident with the development of insulin resistance, and not with excess peripheral adiposity, hyperglycemia, change in trabecular bone volume or hematopoiesis.…”

Section: Nutritional and Environmental Interventionsmentioning

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

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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.

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Marrow Adipose Tissue Expansion Coincides with Insulin Resistance in MAGP1-Deficient Mice

Cited by 17 publications

References 31 publications

Bone Marrow Fat Changes After Gastric Bypass Surgery Are Associated With Loss of Bone Mass

Bone Marrow Fat Changes After Gastric Bypass Surgery Are Associated With Loss of Bone Mass

Development, regulation, metabolism and function of bone marrow adipose tissues

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

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