Marrow Adiposity and Hematopoiesis in Aging and Obesity: Exercise as an Intervention

Patel, Vihitaben S.; Chan, M. Ete; Rubin, Janet; Rubin, Clinton T.

doi:10.1007/s11914-018-0424-1

Cited by 26 publications

(18 citation statements)

References 101 publications

(140 reference statements)

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“…However, visceral fat is also associated with inflammation as reflected by the higher secretion of proinflammatory cytokines such as TNFα and IL‐6, which negatively affect bone metabolism . Finally, obesity leads to an increase in bone marrow fat, a condition that usually occurs in aged individuals . The increase in bone marrow adiposity may indicate a shift in the fate decision of mesenchymal stem cells (MSCs) from osteoblasts to adipocytes, thereby increasing fat accumulation and reducing osteoblastic activity.…”

Section: Introductionmentioning

confidence: 99%

Contributions of Dickkopf‐1 to Obesity‐Induced Bone Loss and Marrow Adiposity

et al. 2020

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Low bone strength in overweight individuals is a significant medical problem. One important determinant of mesenchymal stem cell fate into osteoblasts or adipocytes is the Wnt signaling pathway. We recently showed that Dickkopf‐1 (DKK1), a potent Wnt inhibitor, is upregulated in obese mice. In this study, we investigated the role of DKK1 in the pathogenesis of obesity‐induced bone loss using global and tissue‐specific KO mice. Obesity was induced in 8‐week‐old male mice with an inducible global (Rosa26‐CreERT2) or osteoprogenitor‐ (Osx–Cre‐) specific deletion of Dkk1 with a high‐fat diet (HFD) containing 60% fat. After 12 weeks, body weight, bone volume, bone fat mass, and bone turnover were assessed. Dkk1 fl/fl;Rosa26‐CreERT2 mice experienced a similar increase in body weight and white fat pads as control mice. A HFD significantly reduced trabecular bone mass and the bone formation rate in Cre‐ mice and Dkk1 fl/fl;Rosa26‐CreERT2 mice. Interestingly, Dkk1 fl/fl;Rosa26‐CreERT2 mice were protected from HFD‐induced cortical bone loss. Furthermore, a HFD was associated with increased bone marrow fat in the femur, which was less pronounced in Dkk1 fl/fl;Rosa26‐CreERT2 mice. Mice with an osteoprogenitor‐specific Dkk1 deletion showed similar results as the global knockout, showing a protection against HFD‐induced cortical bone loss and an accumulation of bone marrow fat, but a similar decrease in trabecular bone volume. In summary, DKK1 appears to contribute distinctly to cortical, but not trabecular bone loss in obesity. © 2020 The Authors. JBMR Plus published by Wiley Periodicals, Inc. on behalf of American Society for Bone and Mineral Research.

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Section: Introductionmentioning

confidence: 99%

Contributions of Dickkopf‐1 to Obesity‐Induced Bone Loss and Marrow Adiposity

et al. 2020

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“…MAT, derived from the differentiation of mesenchymal stem cells (MSC) into adipocytes, increases in bonefragility states; however, its potential role in promoting bone formation and/or resorption has not been elucidated, despite active investigation. (2)(3)(4)(5)(6)(7)(8)(9)(10)(11) Understanding of MAT has improved with quantification methods that permit exact investigations, including magnetic resonance spectroscopy (MRS) in humans (12)(13)(14)(15) as well as osmium-μCT and MRI with advanced image processing in rodents. (16)(17)(18) Recent work established MAT to be suppressed by exercise, in rodents (16,18) and humans, (19) suggesting that MAT may function similarly to white adipose tissue in a calorie-replete state as an energy depot.…”

Section: Introductionmentioning

confidence: 99%

Exercise Degrades Bone in Caloric Restriction, Despite Suppression of Marrow Adipose Tissue (MAT)

McGrath

Sankaran

Misaghian‐Xanthos

et al. 2019

Journal of Bone and Mineral Research

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Marrow adipose tissue (MAT) and its relevance to skeletal health during caloric restriction (CR) is unknown: It remains unclear whether exercise, which is anabolic to bone in a calorie‐replete state, alters bone or MAT in CR. We hypothesized that response of bone and MAT to exercise in CR differs from the calorie‐replete state. Ten‐week‐old female B6 mice fed a regular diet (RD) or 30% CR diet were allocated to sedentary (RD, CR, n = 10/group) or running exercise (RD‐E, CR‐E, n = 7/group). After 6 weeks, CR mice weighed 20% less than RD, p < 0.001; exercise did not affect weight. Femoral bone volume (BV) via 3D MRI was 20% lower in CR versus RD (p < 0.0001). CR was associated with decreased bone by μCT: Tb.Th was 16% less in CR versus RD, p < 0.003, Ct.Th was 5% less, p < 0.07. In CR‐E, Tb.Th was 40% less than RD‐E, p < 0.0001. Exercise increased Tb.Th in RD (+23% RD‐E versus RD, p < 0.003) but failed to do so in CR. Cortical porosity increased after exercise in CR (+28%, p = 0.04), suggesting exercise during CR is deleterious to bone. In terms of bone fat, metaphyseal MAT/ BV rose 159% in CR versus RD, p = 0.003 via 3D MRI. Exercise decreased MAT/BV by 52% in RD, p < 0.05, and also suppressed MAT in CR (−121%, p = 0.047). Histomorphometric analysis of adipocyte area correlated with MAT by MRI (R2 = 0.6233, p < 0.0001). With respect to bone, TRAP and Sost mRNA were reduced in CR. Intriguingly, the repressed Sost in CR rose with exercise and may underlie the failure of CR‐bone quantity to increase in response to exercise. Notably, CD36, a marker of fatty acid uptake, rose 4088% in CR (p < 0.01 versus RD), suggesting that basal increases in MAT during calorie restriction serve to supply local energy needs and are depleted during exercise with a negative impact on bone. © 2019 The Authors. Journal of Bone and Mineral Research published by American Society for Bone and Mineral Research.

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“…IGF-1 mediates biological effects mostly through binding to IGF-1 receptor and with less affinity to insulin receptor [28,29]. There is a negative correlation between plasma IGF-1 and BMAT formation [30]. In subjects with a severely reduced caloric intake, dysregulation of the growth hormone-IGF-1 axis and low leptin levels are associated with increased BMAT formation [31].…”

Section: Insulin-like Growth Factor-1mentioning

confidence: 99%

Insulin Signaling in Bone Marrow Adipocytes

Tencerová

Okla

Kassem

2019

Curr Osteoporos Rep

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Purpose of Review The goal of this review is to discuss the role of insulin signaling in bone marrow adipocyte formation, metabolic function, and its contribution to cellular senescence in relation to metabolic bone diseases. Recent Findings Insulin signaling is an evolutionally conserved signaling pathway that plays a critical role in the regulation of metabolism and longevity. Bone is an insulin-responsive organ that plays a role in whole body energy metabolism. Metabolic disturbances associated with obesity and type 2 diabetes increase a risk of fragility fractures along with increased bone marrow adiposity. In obesity, there is impaired insulin signaling in peripheral tissues leading to insulin resistance. However, insulin signaling is maintained in bone marrow microenvironment leading to hypermetabolic state of bone marrow stromal (skeletal) stem cells associated with accelerated senescence and accumulation of bone marrow adipocytes in obesity. Summary This review summarizes current findings on insulin signaling in bone marrow adipocytes and bone marrow stromal (skeletal) stem cells and its importance for bone and fat metabolism. Moreover, it points out to the existence of differences between bone marrow and peripheral fat metabolism which may be relevant for developing therapeutic strategies for treatment of metabolic bone diseases.with enhanced insulin sensitivity, glucose uptake, and oxidative phosphorylation. This metabolic phenotype of BMSC in obesity results in increased ROS production, which might lead to creation of senescent bone marrow microenvironment and stem cell exhaustion contributing to bone fragility in metabolic bone diseases Curr Osteoporos Rep (2019) 17:44 -454 6 447

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Marrow Adiposity and Hematopoiesis in Aging and Obesity: Exercise as an Intervention

Cited by 26 publications

References 101 publications

Contributions of Dickkopf‐1 to Obesity‐Induced Bone Loss and Marrow Adiposity

Contributions of Dickkopf‐1 to Obesity‐Induced Bone Loss and Marrow Adiposity

Exercise Degrades Bone in Caloric Restriction, Despite Suppression of Marrow Adipose Tissue (MAT)

Insulin Signaling in Bone Marrow Adipocytes

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