Marrow adiposity as an indicator for insulin resistance in postmenopausal women with newly diagnosed type 2 diabetes – an investigation by chemical shift-encoded water-fat MRI

Zhu, Lequn; Zheng, Xu; Li, Guanwu; Wang, Ying; Li, Xuefeng; Xiao, Shi; Lin, Hui‐Yi; Chang, Shixin

doi:10.1016/j.ejrad.2019.02.020

Cited by 25 publications

(25 citation statements)

References 43 publications

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“…The fat fraction within the bone marrow is well-known to accrue and to negatively correlate with bone density in aging (1) and postmenopausal (2) subjects. Moreover, the bone marrow fat fraction can increase in Type 2 diabetic patients (3–5) and is found closely associated with a poor glycemic control (5–9) which broadens its involvement in the compromised bone quality reported in such metabolic pathologies. Several in vitro studies and first ex vivo characterization of BMAds have emphasized how these specific adipocytes diverge from typical extramedullary adipocytes and release various products—adipokines, growth factors, inflammatory mediators, fatty acids—which can affect the differentiation, function, or survival of the bone-forming osteoblasts and/or the bone-resorbing osteoclasts (10).…”

Section: Introductionmentioning

confidence: 99%

High Glucose Level Impairs Human Mature Bone Marrow Adipocyte Function Through Increased ROS Production

Rharass

Lucas

2019

Front. Endocrinol.

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Bone marrow adipocytes (BMAds) accumulate in aging, menopause, and metabolic diseases such as Type 2 diabetes. These osteoporotic conditions are associated with oxidative stress and hyperglycemia which are both considered as critical factors underlying bone fragility. Glucose excess and reactive oxygen species (ROS) are known to favor adipogenesis over osteoblastogenesis. In this study, we investigated whether high glucose exposure could determine dysfunction of mature BMAds, specifically through ROS production. The effects of low (LG, 5 mM) or high glucose (HG, 25 mM) concentrations were examined using human bone mesenchymal stromal cells (hBMSCs) in the time course of differentiation, and, up to 21 days once adipocytes were mature. HG did not alter the adipocyte differentiation process of hBMSCs. Yet, after 21 days under HG exposure, PPARG, CEBPA, and adiponectin mRNA expressions were decreased. These alterations were also observed following adipogenic inducer withdrawal as well as in adipocytes fully differentiated in LG then cultured in HG for the last 11 days. Without inducers, HG condition also led to decreased leptin mRNA level. Importantly, intracellular and extracellular ROS concentrations measured using Amplex Red were significantly raised by 50% under HG exposure. This rise was observed once adipocytes ended differentiation and was reproduced within the different cell culture settings without any cytotoxicity. Among genes involved in ROS metabolism, the mRNA level of the H2O2 generating enzyme NOX4 was found upregulated in the presence of HG. Following cell separation, mature BMAds were shown to overproduce ROS and to display the gene alterations in contrast to non-lipid-laden cells. Finally, a non-lethal treatment with a pro-oxidant agent under LG condition reduces the mRNA levels of PPARG, adiponectin, and leptin as the HG condition does in the absence of inducers, and amplifies the effect of glucose excess on gene expression. HG concentration drives mature BMAds toward altered expression of the main adipokines and transcriptional factors. These perturbations are associated with a rise in ROS generation likely mediated through enhanced expression of NOX4. Mature BMAds are thus responsive to changes in glucose and ROS concentrations, which is relevant regarding with their phenotype and function in age- or metabolic disease-related osteoporosis.

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Section: Introductionmentioning

confidence: 99%

High Glucose Level Impairs Human Mature Bone Marrow Adipocyte Function Through Increased ROS Production

Rharass

Lucas

2019

Front. Endocrinol.

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“…Diabetic women with hemoglobin A1C levels > 7%, exhibit higher vertebral BMAT content of L1-L3 compared with patients with HbA1c levels ≤ 7% [37]. Moreover, a high level of blood glucose inhibits the proliferation and migration of BMSC and promotes marrow adipocyte formation but not osteoblastogenesis [15]. These studies demonstrate that BMAT formation is affected by glycemic status and glycemic control; however, further studies are needed to determine whether these effects are independent of insulin action.…”

Section: Glucosementioning

confidence: 74%

“…Another evidence about the role of BMAT to participate in regulating whole body energy metabolism is its ability to respond to insulin [15], to activate Sirt1, a key cellular energy sensor, and to induce a thermogenic gene program [16]. BMAT may contribute to systemic glucose and fatty acid clearance [3].…”

Section: Introductionmentioning

confidence: 99%

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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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“…In previous studies ectopic, intramuscular fat accumulation has been shown to be associated with decreasing insulin sensitivity and metabolic diseases 17,18 . Furthermore, vertebral bone marrow fat content has also been shown to be correlated with insulin resistance in postmenopausal women diagnosed with Type 2 Diabetes, which suggests the use of vertebral PDFF for screening of obese subjects with a tendency towards developing metabolic syndrome 19 .…”

mentioning

confidence: 98%

Age- and BMI-related variations of fat distribution in sacral and lumbar bone marrow and their association with local muscle fat content

Burian

Syväri

Dieckmeyer

et al. 2020

Sci Rep

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this analysis investigated the age-and BMi-related variations of fat distribution in sacral and lumbar bone marrow and their association with local muscle fat content in order to detect fat distribution patterns and variations in healthy adults using proton density fat fraction (pDff) measurements. A six-echo 3D spoiled gradient-echo sequence was used for chemical shift encoding-based waterfat separation at the sacral and lower lumbar region in 103 healthy volunteers. PDFF values of the sacrum, 5 th lumbar vertebral body, the gluteal and paraspinal muscles were determined. correlation with age was significant (p < 0.05) for PDFF of the sacrum (men (m): r = 0.58; women (w): r = 0.54), L5 (m: r = 0.58; w: r = 0.54), the gluteal (m: r = 0.51; w: r = 0.44) and paraspinal (m: r = 0.36; w: r = 0.49) muscles in both genders. BMI correlated significantly with the paraspinal musculature in men (r = 0.46) and women (r = 0.33). Correlation testing revealed significant correlations (p < 0.05) between the two osseous (m: r = 0.63, w: r = 0.75) and the muscle compartments (m: r = 0.63, w: r = 0.33) in both genders. Bone marrow and muscle fat infiltration patterns were not significantly associated with each other at the sacral and lower lumbar spine region. the presented data suggest that the two compartments may have distinct pathophysiological fat infiltration patterns. However, further clinical studies are needed to support the results.

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Marrow adiposity as an indicator for insulin resistance in postmenopausal women with newly diagnosed type 2 diabetes – an investigation by chemical shift-encoded water-fat MRI

Cited by 25 publications

References 43 publications

High Glucose Level Impairs Human Mature Bone Marrow Adipocyte Function Through Increased ROS Production

High Glucose Level Impairs Human Mature Bone Marrow Adipocyte Function Through Increased ROS Production

Insulin Signaling in Bone Marrow Adipocytes

Age- and BMI-related variations of fat distribution in sacral and lumbar bone marrow and their association with local muscle fat content

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