RESUMO
OBJECTIVE: Brown adipose tissue (BAT) controls metabolic rate through thermogenesis. As its regulatory factors during the transition from hyperthyroidism to euthyroidism are not well established, our study investigated the relationships between supraclavicular brown adipose tissue (sBAT) activity and physiological/metabolic changes with changes in thyroid status. DESIGN: Participants with newly diagnosed Graves' disease were recruited. A thionamide antithyroid drug (ATD) such as carbimazole (CMZ) or thiamazole (TMZ) was prescribed in every case. All underwent energy expenditure (EE) measurement and supraclavicular infrared thermography (IRT) within a chamber calorimeter, as well as 18F-fluorodeoxyglucose (18F-FDG) positron-emission tomography/magnetic resonance (PET/MR) imaging scanning, with clinical and biochemical parameters measured during hyperthyroidism and repeated in early euthyroidism. PET sBAT mean/maximum standardized uptake value (SUV mean/max), MR supraclavicular fat fraction (sFF) and mean temperature (Tscv) quantified sBAT activity. RESULTS: Twenty-one (16 female/5 male) participants aged 39.5 ± 2.5 years completed the study. The average duration to attain euthyroidism was 28.6 ± 2.3 weeks. Eight participants were BAT-positive while 13 were BAT-negative. sFF increased with euthyroidism (72.3 ± 1.4% to 76.8 ± 1.4%; P < 0.01), but no changes were observed in PET SUV mean and Tscv. Significant changes in serum-free triiodothyronine (FT3) levels were related to BAT status (interaction P value = 0.04). FT3 concentration at hyperthyroid state was positively associated with sBAT PET SUV mean (r = 0.58, P = 0.01) and resting metabolic rate (RMR) (P < 0.01). CONCLUSION: Hyperthyroidism does not consistently lead to a detectable increase in BAT activity. FT3 reduction during the transition to euthyroidism correlated with BAT activity.
Assuntos
Tecido Adiposo Marrom/metabolismo , Hipertireoidismo/metabolismo , Hipertireoidismo/reabilitação , Tecido Adiposo Marrom/diagnóstico por imagem , Tecido Adiposo Marrom/efeitos dos fármacos , Adulto , Idoso , Antitireóideos/farmacologia , Antitireóideos/uso terapêutico , Composição Corporal/efeitos dos fármacos , Composição Corporal/fisiologia , Carbimazol/uso terapêutico , Metabolismo Energético/efeitos dos fármacos , Metabolismo Energético/fisiologia , Feminino , Fluordesoxiglucose F18 , Doença de Graves/tratamento farmacológico , Doença de Graves/metabolismo , Doença de Graves/reabilitação , Humanos , Hipertireoidismo/diagnóstico , Hipertireoidismo/tratamento farmacológico , Imageamento por Ressonância Magnética , Masculino , Metimazol/uso terapêutico , Pessoa de Meia-Idade , Tomografia por Emissão de Pósitrons , Indução de Remissão , Singapura , Termogênese/efeitos dos fármacos , Termogênese/fisiologia , Glândula Tireoide/diagnóstico por imagem , Glândula Tireoide/efeitos dos fármacos , Glândula Tireoide/metabolismo , Glândula Tireoide/fisiologia , Adulto JovemRESUMO
Bone remodeling consists of resorption by osteoclasts followed by formation by osteoblasts, and osteoclasts are a source of bone formation-stimulating factors. Here we utilize osteoclast ablation by denosumab (DMAb) and RNA-sequencing of bone biopsies from postmenopausal women to identify osteoclast-secreted factors suppressed by DMAb. Based on these analyses, LIF, CREG2, CST3, CCBE1, and DPP4 are likely osteoclast-derived coupling factors in humans. Given the role of Dipeptidyl Peptidase-4 (DPP4) in glucose homeostasis, we further demonstrate that DMAb-treated participants have a significant reduction in circulating DPP4 and increase in Glucagon-like peptide (GLP)-1 levels as compared to the placebo-treated group, and also that type 2 diabetic patients treated with DMAb show significant reductions in HbA1c as compared to patients treated either with bisphosphonates or calcium and vitamin D. Thus, our results identify several coupling factors in humans and uncover osteoclast-derived DPP4 as a potential link between bone remodeling and energy metabolism.
Assuntos
Osso e Ossos/metabolismo , Metabolismo Energético , Osteoblastos/metabolismo , Osteoclastos/metabolismo , Idoso , Idoso de 80 Anos ou mais , Animais , Remodelação Óssea , Proteínas de Ligação ao Cálcio/genética , Proteínas de Ligação ao Cálcio/metabolismo , Denosumab/administração & dosagem , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/genética , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Tipo 2/fisiopatologia , Dipeptidil Peptidase 4/genética , Dipeptidil Peptidase 4/metabolismo , Metabolismo Energético/efeitos dos fármacos , Feminino , Humanos , Pessoa de Meia-Idade , Osteoblastos/efeitos dos fármacos , Osteoclastos/efeitos dos fármacos , Estudos Prospectivos , Proteínas Repressoras/genética , Proteínas Repressoras/metabolismo , Proteínas Supressoras de Tumor/genética , Proteínas Supressoras de Tumor/metabolismoRESUMO
Peak bone mass is the maximum bone mass that accrues during growth and development. Consolidation of peak bone mass normally occurs during early adulthood. Low peak bone mass results from failure to achieve peak bone mass genetic potential, primarily due to bone loss caused by a variety of conditions or processes occurring at younger ages than usual. Recognized causes of low peak bone mass include genetic causes, endocrine disorders, nutritional disorders, chronic diseases of childhood or adolescence, medications, and idiopathic factors.
Assuntos
Densidade Óssea , Osso e Ossos/patologia , Osso e Ossos/fisiopatologia , Doenças do Sistema Endócrino/complicações , Distúrbios Nutricionais/complicações , Osteoporose/etiologia , Densidade Óssea/genética , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/complicações , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/fisiopatologia , Doenças do Sistema Endócrino/fisiopatologia , Feminino , Humanos , Distúrbios Nutricionais/fisiopatologia , Tamanho do Órgão , Osteoporose/genéticaRESUMO
Laboratory biochemical testing is critical to the clinical understanding of bone disorders. Patients with skeletal diseases have underlying themes in their pathophysiology that would be impossible to detect without biochemical assessment of serum and urine minerals, vitamin D, parathyroid hormone, parathyroid hormone-related peptide, and bone turnover markers. Bone disorders are caused by abnormalities in signaling pathways that affect bone formation and resorption. Therapies for common bone diseases were developed in direct response to underlying biochemical abnormalities.
Assuntos
Doenças Ósseas/diagnóstico , Técnicas de Laboratório Clínico , Biomarcadores , Remodelação Óssea , Reabsorção Óssea , Osso e Ossos , Cálcio , Humanos , Hormônio Paratireóideo , Vitamina DRESUMO
The treatment of osteoporosis is generally either by inhibition of bone resorption with antiresorptive agents or by stimulation of bone formation with anabolic agents. Currently, teriparatide (recombinant human parathyroid hormone 1-34 [rhPTH (1-34)]) is the only available approved anabolic agent in the U.S. Other anabolic agents are under investigation however. Abaloparatide is recombinant human parathyroid hormone-related peptide 1-34. This agent is an anabolic agent that appears more potent than teriparatide, and it may have more rapid onset of fracture reduction than teriparatide. It is currently undergoing FDA review, with approval expected in 2017.