Fatty acid oxidation by the osteoblast is required for normal bone acquisition in a sex- and diet-dependent manner

Kim, Soohyun P.; Li, Zhu; Zoch, Meredith L.; Frey, Julie L.; Bowman, Caitlyn E.; Kushwaha, Priyanka; Ryan, Kathleen A.; Goh, Brian C.; Scafidi, Susanna; Pickett, Julie E.; Faugère, Marie-Claude; Kershaw, Erin E.; Thorek, Daniel L.J.; Clemens, Thomas L.; Wolfgang, Michael J.; Riddle, Ryan C.

doi:10.1172/jci.insight.92704

Cited by 91 publications

(109 citation statements)

References 70 publications

(85 reference statements)

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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. Moreover, fatty acid β-oxidation markers rise in bone in the setting of exercise, concomitant with increased bone quantity; this along with research (9,20) demonstrating the reliance of the osteoblast on β-oxidation support MAT's role as an energy depot. (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: 81%

“…(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. Moreover, fatty acid β-oxidation markers rise in bone in the setting of exercise, concomitant with increased bone quantity; this along with research (9,20) demonstrating the reliance of the osteoblast on β-oxidation support MAT's role as an energy depot.…”

Section: Introductionmentioning

confidence: 81%

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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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Section: Introductionmentioning

confidence: 81%

Section: Introductionmentioning

confidence: 81%

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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“…(151,152) Decrease inflammation (150) Promote osteoblastogenesis (151,152) Increase inflammation (150) Decrease osteoblastogenesis (151,152) Osteoclasts Promote osteoclastogenesis? (153,154) Increase BMD (155)(156)(157) Inhibit bone resorption and osteoclastogenesis (158,159) Promote osteoclastogenesis? (159)(160)(161) BMD, bone mineral density; PUFAs, polyunsaturated fatty acids; SFAs, saturated fatty acids.…”

Section: Emerging Dietary Issues: Polyunsaturated Fatty Acids and Polmentioning

confidence: 99%

“…The role of SFAs and n-6 PUFAs in osteoclasts is unclear, and there is conflicting evidence as to whether they upregulate or downregulate osteoclastogenesis (161,187). N-3 PUFAs showed inhibitory effects on osteoclast functions and were associated with increased BMD (155)(156)(157)(158)(159). As to the n-6 PUFA arachidonic acid, it was found to either upor down-regulate osteclastogenesis (161,187).…”

Section: Emerging Dietary Issues: Polyunsaturated Fatty Acids and Polmentioning

confidence: 99%

The Bones of Children With Obesity

et al. 2020

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Excess adiposity in childhood may affect bone development, ultimately leading to bone frailty. Previous reports showing an increased rate of extremity fractures in children with obesity support this fear. On the other hand, there is also evidence suggesting that bone mineral content is higher in obese children than in normal weight peers. Both adipocytes and osteoblasts derive from multipotent mesenchymal stem cells (MSCs) and obesity drives the differentiation of MSCs toward adipocytes at the expense of osteoblast differentiation. Furthermore, adipocytes in bone marrow microenvironment release a number of pro-inflammatory and immunomodulatory molecules that up-regulate formation and activation of osteoclasts, thus favoring bone frailty. On the other hand, body adiposity represents a mechanical load, which is beneficial for bone accrual. In this frame, bone quality, and structure result from the balance of inflammatory and mechanical stimuli. Diet, physical activity and the hormonal milieu at puberty play a pivotal role on this balance. In this review, we will address the question whether the bone of obese children and adolescents is unhealthy in comparison with normal-weight peers and discuss mechanisms underlying the differences in bone quality and structure. We anticipate that many biases and confounders affect the clinical studies conducted so far and preclude us from achieving robust conclusions. Sample-size, lack of adequate controls, heterogeneity of study designs are the major drawbacks of the existing reports. Due to the increased body size of children with obesity, dual energy absorptiometry might overestimate bone mineral density in these individuals. Magnetic resonance imaging, peripheral quantitative CT (pQCT) scanning and high-resolution pQCT are promising techniques for the accurate estimate of bone mineral content in obese children. Moreover, no longitudinal study on the risk of incident osteoporosis in early adulthood of children and adolescents with obesity is available. Finally, we will address emerging dietary issues (i.e., the likely benefits for the bone health of polyunsaturated fatty acids and polyphenols) since an healthy diet (i.e., the Mediterranean diet) with balanced intake of certain nutrients associated with physical activity remain the cornerstones for achieving an adequate bone accrual in young individuals regardless of their adiposity degree.

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“…Insulin exerts anabolic effect on the bone metabolism and it has a critical role in the regulation of skeletal development and bone integrity [48]. Insulin signaling represents a key metabolic pathway important for the bioenergetic demand of bone cells [49][50][51][52][53]. Our group has recently examined the effects of obesity on BMAT and its role in regulating skeletal energy demands.…”

Section: Insulin Signaling In Bone Marrow Adipocytes In Relation To Omentioning

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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Fatty acid oxidation by the osteoblast is required for normal bone acquisition in a sex- and diet-dependent manner

Cited by 91 publications

References 70 publications

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

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

The Bones of Children With Obesity

Insulin Signaling in Bone Marrow Adipocytes

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