RESUMO
Familial partial lipodystrophies (FPLD) are rare diseases characterized by selective loss of subcutaneous adipose tissue at different sites. This cross-sectional observational study aimed to estimate adipose tissue in the bone marrow (BMAT), intra (IMCL) and extra-myocyte lipids (EMCL), and define the bone phenotype in the context of FPLD2/Dunnigan syndrome (DS). The subjects comprised 23 controls (C) and 18 DS patients, matched by age, weight and height. Blood samples, dual-energy X-ray absorptiometry for bone mineral density (BMD) and trabecular bone score (TBS) and 1H-spectroscopy using magnetic resonance to estimate BMAT in the lumbar spine, IMCL, EMCL and osteoclastogenesis were assessed. The prevalence of diabetes mellitus was 78% in DS patients. Glucose, HbA1c, triglycerides, insulin and HOMA-IR levels were elevated in DS, whereas HDLc, 25(OH)D, PTH and osteocalcin levels were reduced. BMD was similar between groups at all sites, except 1/3 radius, which was lower in DS group. TBS was reduced in DS. DS presented increased osteoclastogenesis and elevated BMAT, with greater saturation levels and higher IMCL than the C group. HOMA-IR and EMCL were negatively associated with TBS; osteocalcin and EMCL were correlated negatively with BMD. This study contributes to refining the estimation of adipose tissue in DS by showing increased adiposity in the lumbar spine and muscle tissue. DXA detected lower TBS and BMD in the 1/3 radius, suggesting impairment in bone quality and that bone mass is mainly affected in the cortical bone.
Assuntos
Adiposidade , Lipodistrofia Parcial Familiar , Humanos , Densidade Óssea , Estudos Transversais , Obesidade , OsteocalcinaRESUMO
Anthropomorphic measures among type 1 diabetic patients are changing as the obesity epidemic continues. Excess fat mass may impact bone density and ultimately fracture risk. We studied the interaction between bone and adipose tissue in type 1 diabetes subjects submitted to two different clinical managements: (I) conventional insulin therapy or (II) autologous nonmyeloablative hematopoietic stem-cell transplantation (AHST). The study comprised 3 groups matched by age, gender, height and weight: control (C = 24), type 1 diabetes (T1D = 23) and type 1 diabetes treated with AHST (T1D-AHST = 9). Bone mineral density (BMD) and trabecular bone score (TBS) were assessed by dual X-ray absorptiometry (DXA). 1H Magnetic resonance spectroscopy was used to assess bone marrow adipose tissue (BMAT) in the L3 vertebra, and abdominal magnetic resonance imaging was used to assess intrahepatic lipids (IHL), visceral (VAT) and subcutaneous adipose tissue (SAT). Individuals conventionally treated for T1D were more likely to be overweight (C = 23.8 ± 3.7; T1D = 25.3 ± 3.4; T1D-AHST = 22.5 ± 2.2 Kg/m2; p > 0.05), but there was no excessive lipid accumulation in VAT or liver. Areal BMD of the three groups were similar at all sites; lumbar spine TBS (L3) was lower in type 1 diabetes (p < 0.05). Neither SAT nor VAT had any association with bone parameters. Bone marrow adipose tissue (BMAT) lipid profiles were similar among groups. BMAT saturated lipids were associated with cholesterol, whereas unsaturated lipids had an association with IGF1. Overweight and normal weight subjects with type 1 diabetes have normal areal bone density, but lower trabecular bone scores. Adipose distribution is normal and BMAT volume is similar to controls, irrespective of clinical treatment.
Assuntos
Tecido Adiposo/diagnóstico por imagem , Medula Óssea/diagnóstico por imagem , Diabetes Mellitus Tipo 1/diagnóstico por imagem , Vértebras Lombares/diagnóstico por imagem , Absorciometria de Fóton , Adulto , Composição Corporal , Densidade Óssea , Remodelação Óssea , Osso e Ossos , Brasil , Osso Esponjoso/diagnóstico por imagem , Estudos de Casos e Controles , Estudos Transversais , Diabetes Mellitus Tipo 1/terapia , Feminino , Transplante de Células-Tronco Hematopoéticas , Humanos , Hipoglicemiantes/uso terapêutico , Insulina/uso terapêutico , Gordura Intra-Abdominal/diagnóstico por imagem , Metabolismo dos Lipídeos , Fígado/diagnóstico por imagem , Fígado/metabolismo , Masculino , Pessoa de Meia-Idade , Espectroscopia de Prótons por Ressonância Magnética , Gordura Subcutânea/diagnóstico por imagem , Transplante Autólogo , Adulto JovemRESUMO
Oxidative stress (OS) derived from an increase in intracellular reactive oxygen species (ROS) is a major determinant of aging and lifespan. It has also been associated with several age-related disorders, like postmenopausal osteoporosis of Mesenchymal stem cells (MSCs). MSCs are the common precursors for osteoblasts and adipocytes; appropriate commitment and differentiation of MSCs into a specific phenotype is modulated, among other factors, by ROS balance. MSCs have shown more resistance to ROS than differentiated cells, and their redox status depends on complex and abundant anti-oxidant mechanisms. The purpose of this work was to analyze in real time, H2 O2 signaling in individual h-MSCs, and to compare the kinetic parameters of H2 O2 management by cells derived from both control (c-) and osteoporotic (o-) women. For these purposes, cells were infected with a genetically encoded fluorescent biosensor named HyPer, which is specific for detecting H2 O2 inside living cells. Subsequently, cells were sequentially challenged with 50 and 500 µM H2 O2 pulses, and the cellular response was recorded in real time. The results demonstrated adequate expression of the biosensor allowing registering fluorescence from HyPer at a single cell level. Comparison of the response of c- and o-MSCs to the oxidant challenges demonstrated improved antioxidant activity in o-MSCs. This was further corroborated by measuring the relative expression of mRNAs for catalase, superoxide dismutase-1, thioredoxine, and peroxiredoxine, as well as by cell-surviving capacity under short-term H2 O2 treatment. We conclude that functional differences exist between healthy and osteoporotic human MSCs. The mechanism for these differences requires further study. J. Cell. Biochem. 118: 585-593, 2017. © 2016 Wiley Periodicals, Inc.
Assuntos
Antioxidantes/metabolismo , Células da Medula Óssea/metabolismo , Peróxido de Hidrogênio/metabolismo , Células-Tronco Mesenquimais/metabolismo , Osteoporose Pós-Menopausa/metabolismo , Oxirredutases/metabolismo , Transdução de Sinais , Idoso , Células da Medula Óssea/patologia , Células Cultivadas , Feminino , Humanos , Células-Tronco Mesenquimais/patologia , Pessoa de Meia-Idade , Osteoporose Pós-Menopausa/patologiaRESUMO
Adipocytes are heterogeneous cells strongly linked to energy storage and disposal. In parallel, adipocytes are endowed with an extensive portfolio of endocrine molecules, whose secretion varies depending on nutritional status. Marrow adipose tissue (MAT) has specific characteristics that are not shared by white (WAT) or brown (BAT) adipose tissue. First, marrow adipocytes and osteoblasts are terminally differentiated cells that originate from the same bone marrow mesenchymal stromal cell. Differently from WAT adipocytes, marrow adipocytes expand under conditions of energy restriction and seem to be not influenced by energy surplus, at least in humans. Over the last few years, several lines of evidence have suggested that bone cells and MAT are mutually connected regarding the modulation of both energy metabolism and bone remodeling. Adipokines (e.g., adiponectin, leptin, and chemerin), incretins (GLP1 and GIP), and several classical hormones (e.g., GH and insulin) are biochemical components involved in the modulation of bone remodeling, marrow adipogenesis, and energy metabolism. As expected, metabolic and nutritional diseases such as diabetes mellitus and anorexia nervosa (AN) greatly affect MAT quantity and quality as well as bone strength. Although the interest in MAT started recently, the rapid advances in current technology have expedited unprecedented growth of knowledge in this area. The present review intends to give to the reader an up-to-date perspective about MAT structure and physiology as well as its involvement in metabolic and nutritional diseases such as diabetes mellitus and ano-rexia. © 2018 American Physiological Society. Compr Physiol 8:315-349, 2018.
Assuntos
Adipócitos/citologia , Tecido Adiposo/citologia , Células da Medula Óssea/citologia , Adipócitos/patologia , Adipócitos/fisiologia , Tecido Adiposo/diagnóstico por imagem , Tecido Adiposo/patologia , Anorexia Nervosa/patologia , Biópsia , Medula Óssea/diagnóstico por imagem , Células da Medula Óssea/patologia , Células da Medula Óssea/fisiologia , Diabetes Mellitus/patologia , Hormônios/fisiologia , Humanos , Imageamento por Ressonância Magnética , Osteoporose/patologia , Tomografia Computadorizada por Raios XRESUMO
The function of marrow adipocytes and their origin has not been defined although considerable research has centered on their presence in certain conditions, such as osteoporosis. Less work has focused on the qualitative aspects of marrow fat. Bone marrow serum is composed of multiple nutrients that almost certainly relate to functional aspects of the niche. Previous studies using non-invasive techniques have shown that osteoporotic individuals have more marrow fat and that the ratio of saturated: unsaturated fatty acid is high. We recently reported that bone marrow sera from osteoporotic patients with fracture showed a switch toward decreased content of total saturated versus unsaturated fatty acids, compared to patients without fracture highlighting a dynamic relationship between the composition of fatty acids in the bone microenvironment and the metabolic requirements of cells. The relative distribution of fatty acids differed considerably from that in the serum providing further evidence that energy utilization is high and that marrow adipocytes may contribute to this pool. Whether these lipids can affect osteoblast function in a positive or negative manner is still not certain but will require further investigation.
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Bone marrow adipose tissue (BMAT) is associated with low bone mass, although the functional consequences for skeletal maintenance of increased BMAT are currently unclear. BMAT might have a role in systemic energy metabolism, and could be an energy source as well as an endocrine organ for neighboring bone cells, releasing cytokines, adipokines and free fatty acids into the bone marrow microenvironment. The aim of the present report was to compare the fatty acid composition in the bone marrow supernatant fluid (BMSF) and blood plasma of postmenopausal women women (65-80 years old). BMSF was obtained after spinning the aspirated bone marrow samples; donors were classified as control, osteopenic or osteoporotic after dual-energy X-ray absorptiometry. Total lipids from human bone marrow fluid and plasma were extracted, converted to the corresponding methyl esters, and finally analyzed by a gas chromatographer coupled with a mass spectrometer. Results showed that fatty acid composition in BMSF was dynamic and distinct from blood plasma, implying significance in the locally produced lipids. The fatty acid composition in the BMSF was enriched in saturated fatty acid and decreased in unsaturated fatty acids as compared to blood plasma, but this relationship switched in women who suffered a hip fracture. On the other hand, there was no relationship between BMSF and bone mineral density. In conclusion, lipid composition of BMSF is distinct from the circulatory compartment, most likely reflecting the energy needs of the marrow compartment. J. Cell. Biochem. 117: 2370-2376, 2016. © 2016 Wiley Periodicals, Inc.
Assuntos
Biomarcadores/metabolismo , Medula Óssea/metabolismo , Ácidos Graxos/metabolismo , Fraturas do Quadril/diagnóstico , Osteoporose Pós-Menopausa/complicações , Idoso , Idoso de 80 Anos ou mais , Densidade Óssea , Cromatografia Gasosa , Feminino , Fraturas do Quadril/etiologia , Fraturas do Quadril/metabolismo , Humanos , Pós-MenopausaRESUMO
Bone mineral, adipose tissue and energy metabolism are interconnected by a complex and multilevel series of networks. Calcium and phosphorus are utilized for insulin secretion and synthesis of high energy compounds. Adipose tissue store lipids and cholecalciferol, which, in turn, can influence calcium balance and energy expenditure. Hormones long-thought to solely modulate energy and mineral homeostasis may influence adipocytic function. Osteoblasts are a target of insulin action in bone. Moreover, endocrine mediators, such as osteocalcin, are synthesized in the skeleton but regulate carbohydrate disposal and insulin secretion. Finally, osteoblasts and adipocytes originate from the same mesenchymal progenitor. The mutual crosstalk between osteoblasts and adipocytes within the bone marrow microenvironment plays a crucial role in bone remodeling. In the present review we provide an overview of the reciprocal control between bone and energy metabolism and its clinical implications.
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Vitamin D an ancient secosteroid is essential for mineral homeostasis, bone remodeling, immune modulation, and energy metabolism. Recently, debates have emerged about the daily vitamin D requirements for healthy and elderly adults, the safety and efficacy of long term supplementation and the role of vitamin D deficiency in several chronic disease states. Since this molecule acts as both a vitamin and a hormone, it should not be surprising that the effects of supplementation are multi-faceted and complex. Yet despite significant progress in the last decade, our understanding of vitamin D physiology and the clinical relevance of low circulating levels of this vitamin remains incomplete. The present review provides the reader with a comprehensive and up-to-date understanding of vitamin D requirements and safety. It also raises some provocative research questions.
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Vitamina D/efeitos adversos , Vitamina D/metabolismo , Animais , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Humanos , Estações do Ano , Pigmentação da Pele/efeitos da radiação , Luz Solar , Vitamina D/sangue , Deficiência de Vitamina D/metabolismoRESUMO
The formation, maintenance, and repair of bone tissue involve close interlinks between two stem cell types housed in the bone marrow: the hematologic stem cell originating osteoclasts and mesenchymal stromal cells (MSCs) generating osteoblasts. In this review, we consider malfunctioning of MSCs as essential for osteoporosis. In osteoporosis, increased bone fragility and susceptibility to fractures result from increased osteoclastogenesis and insufficient osteoblastogenesis. MSCs are the common precursors for both osteoblasts and adipocytes, among other cell types. MSCs' commitment towards either the osteoblast or adipocyte lineages depends on suitable regulatory factors activating lineage-specific transcriptional regulators. In osteoporosis, the reciprocal balance between the two differentiation pathways is altered, facilitating adipose accretion in bone marrow at the expense of osteoblast formation; suggesting that under this condition MSCs activity and their microenvironment may be disturbed. We summarize research on the properties of MSCs isolated from the bone marrow of control and osteoporotic post-menopausal women. Our observations indicate that intrinsic properties of MSCs are disturbed in osteoporosis. Moreover, we found that the regulatory conditions in the bone marrow fluid of control and osteoporotic patients are significantly different. These conclusions should be relevant for the use of MSCs in therapeutic applications.
Assuntos
Adipogenia/fisiologia , Células da Medula Óssea/patologia , Células-Tronco Mesenquimais/patologia , Osteoporose/fisiopatologia , Animais , Diferenciação Celular/fisiologia , Células Cultivadas , Feminino , Humanos , Osteoblastos/fisiologia , Osteoclastos/fisiologiaRESUMO
The formation, maintenance, and repair of bone tissue involve close interlinks between two stem cell types housed in the bone marrow: the hematologic stem cell originating osteoclasts and mesenchymal stromal cells (MSCs) generating osteoblasts. In this review, we consider malfunctioning of MSCs as essential for osteoporosis. In osteoporosis, increased bone fragility and susceptibility to fractures result from increased osteoclastogenesis and insufficient osteoblastogenesis. MSCs are the common precursors for both osteoblasts and adipocytes, among other cell types. MSCs' commitment towards either the osteoblast or adipocyte lineages depends on suitable regulatory factors activating lineage-specific transcriptional regulators. In osteoporosis, the reciprocal balance between the two differentiation pathways is altered, facilitating adipose accretion in bone marrow at the expense of osteoblast formation; suggesting that under this condition MSCs activity and their microenvironment may be disturbed. We summarize research on the properties of MSCs isolated from the bone marrow of control and osteoporotic post-menopausal women. Our observations indicate that intrinsic properties of MSCs are disturbed in osteoporosis. Moreover, we found that the regulatory conditions in the bone marrow fluid of control and osteoporotic patients are significantly different. These conclusions should be relevant for the use of MSCs in therapeutic applications.
Assuntos
Animais , Feminino , Humanos , Adipogenia/fisiologia , Células da Medula Óssea/patologia , Células-Tronco Mesenquimais/patologia , Osteoporose/fisiopatologia , Células Cultivadas , Diferenciação Celular/fisiologia , Osteoblastos/fisiologia , Osteoclastos/fisiologiaRESUMO
Knowledge about the influence of bone on intermediary metabolism corresponds to a developing area that has gained prominence. The old concept of bone and adipose tissues as inert metabolic tissues, with minor contributions to metabolic adaptations has been reconsidered in light of findings that bone is involved in the development of insulin sensitivity. Similarly adipose tissue exerts important influences on bone mass development and maintenance. Moreover, the use of drugs in the treatment of metabolic disorders such as diabetes mellitus can impact bone metabolism. These networks linking osteoporosis to obesity and diabetes mellitus have reinvigorated investigations in the pathophysiology of osteoporosis. The present review examines this aspect and calls attention to health care providers and potential treatments of skeletal disorder.
Assuntos
Complicações do Diabetes , Obesidade/complicações , Osteoporose/complicações , Tecido Adiposo/metabolismo , Osso e Ossos/metabolismo , Diabetes Mellitus/metabolismo , Humanos , Obesidade/metabolismo , Obesidade/fisiopatologia , Osteoporose/metabolismoRESUMO
Knowledge about the influence of bone on intermediary metabolism corresponds to a developing area that has gained prominence. The old concept of bone and adipose tissues as inert metabolic tissues, with minor contributions to metabolic adaptations has been reconsidered in light of findings that bone is involved in the development of insulin sensitivity. Similarly adipose tissue exerts important influences on bone mass development and maintenance. Moreover, the use of drugs in the treatment of metabolic disorders such as diabetes mellitus can impact bone metabolism. These networks linking osteoporosis to obesity and diabetes mellitus have reinvigorated investigations in the pathophysiology of osteoporosis. The present review examines this aspect and calls attention to health care providers and potential treatments of skeletal disorder.
O estudo sobre a influência do tecido ósseo no metabolismo intermediário corresponde a uma área em desenvolvimento que tem ganho recente destaque. O conceito prévio de que os tecidos ósseo e adiposo seriam metabolicamente inativos foi reconsiderado à luz de estudos que mostram que metabólitos ósseos podem influenciar a sensibilidade à insulina. Da mesma forma, o tecido adiposo exerce influência importante no desenvolvimento e na manutenção da massa óssea. Além disso, o uso de drogas no tratamento de doenças metabólicas como o diabetes melito pode afetar o metabolismo ósseo. A rede de conexões existentes que ligam a osteoporose à obesidade e ao diabetes melito tem revigorado investigações sobre a fisiopatologia da osteoporose. A presente revisão analisa esse aspecto e destaca a necessidade de atenção para esses pontos por parte de serviços de saúde voltados para o atendimento de diabetes melito e da obesidade quanto ao potencial impacto sobre o tecido ósseo.
Assuntos
Humanos , Complicações do Diabetes , Obesidade/complicações , Osteoporose/complicações , Tecido Adiposo/metabolismo , Osso e Ossos/metabolismo , Diabetes Mellitus/metabolismo , Obesidade/metabolismo , Obesidade/fisiopatologia , Osteoporose/metabolismoRESUMO
OBJECTIVE: To clarify the role of physiologic regulators of bone turnover in patients with anorexia nervosa (AN). STUDY DESIGN: Adolescent girls with AN (n = 61) had anthropometric, nutrition, and exercise data acquired, and bone mineral density (BMD) and body composition measured by dual energy x-ray absorptiometry. Serum samples were obtained for hormones, proresorptive cytokines, and bone formation markers, and urine for bone resorption markers. RESULTS: In bivariate correlation analyses, significant (P <.05) predictors of lumbar BMD included height, weight, and exercise. In multiple regression models, these significant relationships held, even after controlling for the duration of amenorrhea and AN. For total body BMD, the same positive predictors were found and percentage of body fat was a negative correlate. For hip BMD, exercise and weight were found to be positive predictors. Dehydroepiandrosterone sulfate (DHEAS) was inversely correlated with N-telopeptides (NTx), and insulin-like growth factor I (IGF-I) was directly correlated with osteocalcin. Proresorptive cytokine levels were low or undetectable. CONCLUSIONS: Exercise and weight were positive predictors of BMD. These data are the first to suggest a relationship between DHEAS and increased bone resorption in AN. IGF-I was correlated with bone formation indices. Low cytokine levels suggest that these factors do not mediate the increased bone resorption of AN.