Marrow Fat and Bone—New Perspectives

Fazeli, Pouneh K.; Horowitz, Mark C.; MacDougald, Ormond A.; Scheller, Erica L.; Rodeheffer, Matthew S.; Rosen, Clifford J.; Klibanski, Anne

doi:10.1210/jc.2012-3634

Cited by 332 publications

(301 citation statements)

References 97 publications

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“…BM adipose tissue (MAT) occupies up to 70% of BM volume in adult humans [31]. MAT volume in bones increases with age and in pathological situations such as aplastic anemia [32].…”

Section: Adipocytes Fatty Acid Metabolism and Hematopoiesismentioning

confidence: 99%

Metabolic regulation of hematopoietic and leukemic stem/progenitor cells under homeostatic and stress conditions

Karigane

Takubo

2017

Int J Hematol

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organisms. HSPCs are composed of hematopoietic stem cells (HSCs) and several types of lineage-biased, but not fully committed, hematopoietic progenitor cells (HPCs). HSC capacities such as self-renewal and multilineage differentiation maintain the whole hematopoietic system over an organism's lifetime [1], and contribute to blood regeneration under stress condition, whereas HPCs reportedly function to maintain the supply of blood cells at steady state [2,3]. The surrounding BM microenvironment or "niche" determines HSC fate, namely its quiescence, symmetric/asymmetric division, differentiation, or migration potential, in both steady state and during stress. It is now evident that metabolic programs operating in HSCs play critical roles in maintaining hematopoietic homeostasis [4], often in response to BM niche signals [5]. Cellular pathways generate various metabolites through enzymatic activity that supplies material used as fuel, building blocks for other factors, or modulators of intra-or intercellular activities (Fig. 1). Despite the fact that numerous biochemical studies have addressed HSC metabolic regulation, numerous gaps in our knowledge of that regulation remain.Recently, novel means to fractionate metabolites using highly sensitive mass spectrometric technology [6] have dramatically facilitated metabolome analysis. These technologies reduce the need for high cell numbers and increase sensitivity of metabolite selection. As a result, metabolome analysis is feasible in rare cell populations such as HSCs. These analyses have revealed that metabolic programs play critical roles in maintaining stem cell "stemness" (Fig. 2). Here we review recent advances in the field of how metabolic changes regulate HSC dynamics under quiescence, proliferation, and differentiation from the viewpoint of each pathway. In addition to the normal HSC system, we also review activity of leukemia-related metabolic pathways, tumor-associated metabolites (oncometabolites), and Abstract Hematopoietic stem cells (HSCs) exhibit multilineage differentiation and self-renewal activities that maintain the entire hematopoietic system during an organism's lifetime. These abilities are sustained by intrinsic transcriptional programs and extrinsic cues from the microenvironment or niche. Recent studies using metabolomics technologies reveal that metabolic regulation plays an essential role in HSC maintenance. Metabolic pathways provide energy and building blocks for other factors functioning at steady state and in stress. Here we review recent advances in our understanding of metabolic regulation in HSCs relevant to cell cycle quiescence, symmetric/asymmetric division, and proliferation following stress and lineage commitment, and discuss the therapeutic potential of targeting metabolic factors or pathways to treat hematological malignancies.

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“…BM adipose tissue (MAT) occupies up to 70% of BM volume in adult humans [31]. MAT volume in bones increases with age and in pathological situations such as aplastic anemia [32].…”

Section: Adipocytes Fatty Acid Metabolism and Hematopoiesismentioning

confidence: 99%

Metabolic regulation of hematopoietic and leukemic stem/progenitor cells under homeostatic and stress conditions

Karigane

Takubo

2017

Int J Hematol

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“…12 This possibility could be addressed using MRI. Following allo-SCT, calcium, vitamin D and post-menopausal hormone replacement fail to prevent bone loss.…”

Section: Dxa Sitementioning

confidence: 99%

Early changes in bone mineral density and trabecular bone score following allogeneic stem cell transplant

Pawłowska

Yang²,

Hamata

et al. 2016

Bone Marrow Transplant

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“…(2) Marrow fat is often associated with low bone mass, as in anorexia nervosa, aging, and osteoporosis, but is also present in normal bone in complex age-, sex-, and sitespecific patterns. (3)(4)(5) Although marrow adipocytes were historically assumed to be neutral, quiescent space fillers, (6) recent studies have demonstrated that marrow adipose tissue has a role in systemic energy metabolism (7,8) and that bone marrow fat mass and bone mass are inversely correlated even within normal subjects.…”

mentioning

confidence: 99%

Bone marrow composition, diabetes, and fracture risk: More bad news for saturated fat

Devlin

2013

Journal of Bone and Mineral Research

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I n this month's issue, Patsch and colleagues(1) offer ample food for thought for anyone interested in marrow adipocytes, the enigmatic endosteal fat cells whose developmental origins, function, and impact on bone mass are currently subjects of active investigation.(2) Marrow fat is often associated with low bone mass, as in anorexia nervosa, aging, and osteoporosis, but is also present in normal bone in complex age-, sex-, and sitespecific patterns. (3)(4)(5) Although marrow adipocytes were historically assumed to be neutral, quiescent space fillers,recent studies have demonstrated that marrow adipose tissue has a role in systemic energy metabolism (7,8) and that bone marrow fat mass and bone mass are inversely correlated even within normal subjects. (9,10) Marrow fat is now understood as a metabolically active depot that can be mobilized in starvation and that exerts potential beneficial as well as deleterious effects on skeletal and overall metabolism. However, many questions remain about exactly how marrow fat might increase fracture risk, and how this risk varies with age, sex, and comorbidities. Patsch and colleagues (1) tackle two key outstanding questions about marrow fat: whether the composition of marrow fat, as opposed to the quantity, is related to fracture risk; and whether there is an interaction between marrow fat, diabetes, and skeletal fragility. To address these questions, the authors measured vertebral bone marrow adiposity via magnetic resonance imaging (MRI), areal bone mineral density (aBMD) by dualenergy X-ray absorptiometry (DXA), and volumetric BMD (vBMD) by quantitative computed tomography (QCT) in the lumbar spine (L 1 -L 3 ) in postmenopausal women with and without prior fracture history and with or without type 2 diabetes. Marrow fat quantification included both the total lipid and the proportions of saturated, unsaturated, and residual lipid, differentiated by the presence or absence of double bonds. Overall, the results corroborate patterns seen in previous studies: aBMD at the hip and spine was highest in women with type 2 diabetes but no fracture, and lowest in nondiabetic women with prior fracture, whereas vBMD of the spine was lower in women with fracture versus women without fracture, both within controls and within diabetics. Interestingly, there were no differences in total marrow fat content among groups, regardless of diabetes or fracture status, in contrast to at least one recent study that found higher vertebral marrow fat in subjects with prevalent vertebral fractures.(11) However, both diabetes and fracture history were correlated with differences in marrow fat composition. As shown in Table 2 in Patsch and colleagues, (1) the degree of unsaturation was lower in individuals with both diabetes and fractures (DMFx) compared to controls without fracture (Co) and diabetics without fracture (DM), and the degree of saturation was higher in DM and DMFx versus Co. In other words, people with diabetes had more saturated marrow fat, and people with diabetes and history of fractu...

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Marrow Fat and Bone—New Perspectives

Cited by 332 publications

References 97 publications

Metabolic regulation of hematopoietic and leukemic stem/progenitor cells under homeostatic and stress conditions

Metabolic regulation of hematopoietic and leukemic stem/progenitor cells under homeostatic and stress conditions

Early changes in bone mineral density and trabecular bone score following allogeneic stem cell transplant

Bone marrow composition, diabetes, and fracture risk: More bad news for saturated fat

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