RESUMO
Pregnancy is characterized by longitudinal maternal, physiological adaptations to support the development of a fetus. One of the cardinal maternal adaptations during a healthy pregnancy is a progressive increase in uterine artery blood flow. This facilitates sufficient blood supply for the development of the placenta and the growing fetus. Regional hemodynamic changes in the uterine circulation, such as a vast reduction in uterine artery resistance, are mainly facilitated by changes in uterine artery reactivity and myogenic tone along with remodeling of the uterine arteries. These regional changes in vascular reactivity have been attributed to pregnancy-induced adaptations of cell-to-cell communication mechanisms, with an emphasis on the interaction between endothelial and vascular smooth muscle cells. Perivascular adipose tissue (PVAT) is considered the fourth layer of the vascular wall and contributes to the regulation of vascular reactivity in most vascular beds and most species. This review focuses on mechanisms of uterine artery reactivity and the role of PVAT in pregnancy-induced maternal vascular adaptations, with an emphasis on the uterine circulation.
Assuntos
Adaptação Fisiológica , Tecido Adiposo , Artéria Uterina , Feminino , Gravidez , Humanos , Artéria Uterina/fisiologia , Tecido Adiposo/irrigação sanguínea , Tecido Adiposo/fisiologia , Adaptação Fisiológica/fisiologia , AnimaisRESUMO
This work extensively studied the vasculature of mice mammary fat pads (BALB/c and C57BL/6) with special reference to haematogenous drainage routes. Mammary fat pads were five pairs (first cervical, second and third thoracic, fourth abdominal and fifth inguinal), bilaterally symmetrical, extending laterally and continuously with the subcutaneous fascia. The superficial cervical artery and vein primarily accomplished the blood vasculature of the first mammary fat pad, while the lateral thoracic and external thoracic arteries and veins supplied the second and third mammary fat pads. The superficial cervical vein (found parallel to the superficial cervical artery) drained into the external jugular vein. The lateral thoracic artery and external thoracic artery branched almost at the same level as the axillary artery (branch of subclavian artery), the latter being more medial in position. However, in some specimens, the branching of both arteries appeared to be at the same level, and their origins were indistinguishable. The lateral thoracic vein that was parallel to the lateral thoracic artery drained to the axillary vein close to the drainage of the external thoracic vein. The lateral thoracic, superficial caudal epigastric, iliolumbar and external thoracic arteries and veins vascularized the fourth mammary fat pad and displayed anastomosis among themselves. The iliolumbar vein (found parallel to the iliolumbar artery) drained into the inferior vena cava. The superficial caudal epigastric vein (found parallel to the superficial caudal epigastric artery (SCaEA)) drained into the femoral vein. Unlike humans, the internal thoracic artery and vein did not participate in the vasculature of mammary fat pads. The SCaEA and vein supplied blood and drained the fifth mammary fat pad. The anatomical continuity of the fourth and fifth mammary fat pads provided common drainage for both mammary fat pads. The BALB/c and C57BL/6 mice strains studied did not differ in topography and size of mammary fat pads. The vascular supply and drainage of the mammary fat pads also did not differ in the strains studied. Only minor variations could be noted in the small veins draining into the lateral thoracic vein. Lateral tributaries seen in the terminal end of the lateral thoracic vein were absent in the C57BL/6 mice.
Assuntos
Tecido Adiposo , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Animais , Camundongos/anatomia & histologia , Camundongos Endogâmicos C57BL/anatomia & histologia , Tecido Adiposo/anatomia & histologia , Tecido Adiposo/irrigação sanguínea , Feminino , Glândulas Mamárias Animais/irrigação sanguínea , Glândulas Mamárias Animais/anatomia & histologia , Artérias Torácicas/anatomia & histologiaRESUMO
PURPOSE: The aim of this study is to investigate the origin and course of the orbital fat arterial supply in the lower eyelid using traditional anatomy and three-dimensional computed tomography (CT). METHODS: Twenty-seven cadaver heads were infused with mercury sulfide contrast media through the ophthalmic artery, maxillary artery, transverse facial artery, and facial artery. CT images were obtained after contrast agent injection, three-dimensional CT scans were reconstructed, and the cadaver heads were dissected. RESULTS: Forty-five qualified hemifaces showed that the orbital fat arterial supply in the lower eyelid originates primarily from the inferomedial muscular trunk (IMT) of the ophthalmic artery and the orbital branch of the infraorbital artery. The medial branch of the IMT terminated at the medial fat pad (35.6%) or the orbital floor (64.4%). The lateral branch terminated at the inferior oblique (IO) muscle (28.9%) or the central and lateral fat pads (17.8%). In 53.3%, the lateral branch extended to the anterior part of the lateral fat pad and terminated in the orbital wall or the zygomaticoorbital foramina. The orbital branch of the infraorbital artery coursed between the orbital floor and the orbital fat, providing supply to the IO muscle, inferior rectus (IR) muscle, nasolacrimal duct, and orbital fat. CONCLUSION: This study elucidated the origin and course of the orbital fat arterial supply in the lower eyelid, which may help to avoid reducing the blood supply of the orbital fat pedicles during surgery. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .
Assuntos
Tecido Adiposo , Cadáver , Pálpebras , Órbita , Tomografia Computadorizada por Raios X , Humanos , Pálpebras/irrigação sanguínea , Pálpebras/anatomia & histologia , Pálpebras/diagnóstico por imagem , Feminino , Tecido Adiposo/irrigação sanguínea , Tecido Adiposo/anatomia & histologia , Órbita/irrigação sanguínea , Órbita/diagnóstico por imagem , Órbita/anatomia & histologia , Masculino , Imageamento Tridimensional , Pessoa de Meia-Idade , Adulto , Relevância ClínicaRESUMO
Arterioles are key determinants of the total peripheral vascular resistance, which, in turn, is a key determinant of arterial blood pressure. However, the amount of protein available from one isolated human arteriole may be less than 5 µg, making proteomic analysis challenging. In addition, obtaining human arterioles requires manual dissection of unfrozen clinical specimens. This limits its feasibility, especially for powerful multicenter clinical studies in which clinical specimens need to be shipped overnight to a research laboratory for arteriole isolation. We performed a study to address low-input, test overnight tissue storage and develop a reference human arteriolar proteomic profile. In tandem mass tag proteomics, use of a booster channel consisting of human induced pluripotent stem cell-derived endothelial and vascular smooth muscle cells (1:5 ratio) increased the number of proteins detected in a human arteriole segment with a false discovery rate of <0.01 from 1051 to more than 3000. The correlation coefficient of proteomic profile was similar between replicate arterioles isolated freshly, following cold storage, or before and after the cold storage (1-way analysis of variance; P = .60). We built a human arteriolar proteomic profile consisting of 3832 proteins based on the analysis of 12 arteriole samples from 3 subjects. Of 1945 blood pressure-relevant proteins that we curated, 476 (12.5%) were detected in the arteriolar proteome, which was a significant overrepresentation (χ2 test; P < .05). These findings demonstrate that proteomic analysis is feasible with arterioles isolated from human adipose tissue following cold overnight storage and provide a reference human arteriolar proteome profile highly valuable for studies of arteriole-related traits.
Assuntos
Tecido Adiposo , Proteômica , Humanos , Arteríolas/metabolismo , Proteômica/métodos , Tecido Adiposo/metabolismo , Tecido Adiposo/irrigação sanguínea , Proteoma/metabolismo , Proteoma/análise , Feminino , Masculino , Adulto , Pessoa de Meia-IdadeRESUMO
The regenerative potential of adipose-derived stromal cells (ASCs) has gained significant attention in regenerative and translational research. In the past, the extraction of these cells from adipose tissue required a multistep enzyme-based process, resulting in a heterogenous cell mix consisting of ACSs and other cells, which are jointly termed the stromal vascular fraction (SVF). More recently introduced mechanical SVF (mSVF) isolation protocols are less time-consuming and bypass regulatory concerns. We recently proposed a protocol that generates mSVF rich in stromal cells based on a combination of emulsification and centrifugation. One current issue in mSVF application for wound therapy application is the lack of a scaffold providing protection from mechanical manipulation and desiccation. Fibrin hydrogels have been shown to be a useful adjunct in cell transfer for wound healing purposes in the past. In the work herein, we delineate the preparation steps of an mSVF-fibrin hydrogel construct as a novel approach for translational research and clinical application.
Assuntos
Fibrina , Fração Vascular Estromal , Hidrogéis , Células Estromais , Tecido Adiposo/irrigação sanguíneaRESUMO
In the research setting, white adipose tissue (WAT) transplantation, also known as fat transplantation, is often used to understand the physiological function of adipocytes or associated stromal vascular cells such as macrophages in the context of local and systemic metabolism. The mouse is the most common animal model used where WAT from a donor is transferred either to a subcutaneous site of the same organism or to a subcutaneous region of a recipient. Here, we describe in detail the procedure for heterologous fat transplantation, and, given the need for survival surgery, peri- and postoperative care and subsequent histological confirmation of fat grafts will also be discussed.
Assuntos
Adipócitos , Tecido Adiposo Branco , Camundongos , Animais , Tecido Adiposo Branco/metabolismo , Adipócitos/metabolismo , Modelos Animais , Tecido Adiposo/irrigação sanguíneaRESUMO
In this study, we explored the relationship between inflammatory adipokine levels and coronary artery disease (CAD). We collected subcutaneous adipose tissues(SAT), pericardial adipose tissues(PAT), and epicardial adipose tissues (EAT) and serum samples from 26 inpatients with CAD undergone coronary artery bypass grafting and 20 control inpatients without CAD. Serum inflammatory adipokines were measured by ELISA. Quantitative real-time PCR and western blot were used to measure gene and protein expression. Adipocyte morphology was assessed by H&E staining. Immunohistochemistry and immunofluorescence were used to measure endothelial and inflammatory markers. Serum pro- and anti-inflammatory adipokine levels were higher and lower, respectively, in the CAD group than those in the control group (P < 0.05). In CAD, the pro-inflammatory adipokine levels via ELISA in EAT and PAT were elevated. Pro-inflammatory adipokine mRNA expression was increased, while anti-inflammatory adipokine mRNA expression decreased, in CAD relative to NCAD in EAT and PAT rather than SAT. In EAT, adipocyte area and macrophage-specific staining were lower, while lymphatic vessel marker expression was higher in CAD. Additionally, the endothelial marker expression in EAT was higher than PAT in CAD. The three tissue types had different blood vessel amounts in CAD. The regulation and imbalance expression of the novel biomarkers, including inflammatory adipokine, macrophage infiltration, angiogenesis, and lymphangiogenesis in EAT and PAT, may be related to the pathogenesis of CAD. The serum levels of inflammatory adipokines may correlate to CAD, which requires large sample size studies to get further validation before clinic practice.
Assuntos
Tecido Adiposo , Doença da Artéria Coronariana , Pericárdio , Humanos , Adipocinas/sangue , Adipocinas/genética , Adipocinas/metabolismo , Tecido Adiposo/irrigação sanguínea , Tecido Adiposo/metabolismo , Tecido Adiposo/fisiopatologia , Biomarcadores/sangue , Biomarcadores/metabolismo , Doença da Artéria Coronariana/sangue , Doença da Artéria Coronariana/genética , Doença da Artéria Coronariana/metabolismo , Doença da Artéria Coronariana/fisiopatologia , Linfangiogênese/fisiologia , Neovascularização Patológica/sangue , Neovascularização Patológica/metabolismo , Neovascularização Patológica/fisiopatologia , Pericárdio/metabolismo , Pericárdio/fisiopatologia , RNA Mensageiro/genética , RNA Mensageiro/metabolismoRESUMO
Adipose tissue (AT) is a highly active and plastic endocrine organ. It secretes numerous soluble molecules known as adipokines, which act locally to AT control the remodel and homeostasis or exert pleiotropic functions in different peripheral organs. Aberrant production or loss of certain adipokines contributes to AT dysfunction associated with metabolic disorders, including obesity. The AT plasticity is strictly related to tissue vascularization. Angiogenesis supports the AT expansion, while regression of blood vessels is associated with AT hypoxia, which in turn mediates tissue inflammation, fibrosis and metabolic dysfunction. Several adipokines can regulate endothelial cell functions and are endowed with either pro- or anti-angiogenic properties. Here we address the role of adipokines in the regulation of angiogenesis. A better understanding of the link between adipokines and angiogenesis will open the way for novel therapeutic approaches to treat obesity and metabolic diseases.
Assuntos
Adipocinas , Tecido Adiposo , Doenças Metabólicas , Humanos , Adipocinas/metabolismo , Tecido Adiposo/irrigação sanguínea , Tecido Adiposo/metabolismo , Inflamação/metabolismo , Doenças Metabólicas/metabolismo , Obesidade/metabolismo , Neovascularização Fisiológica/fisiologiaRESUMO
Neurodegenerative disorders are characterized by the gradual decline and irreversible loss of cognitive functions and CNS structures. As therapeutic recourse stagnates, neurodegenerative diseases will cost over a trillion dollars by 2050. A dearth of preventive and regenerative measures to hinder regression and enhance recovery has forced patients to settle for traditional therapeutics designed to manage symptoms, leaving little hope for a cure. In the last decade, pre-clinical animal models and clinical investigations in humans have demonstrated the safety and promise of an emerging cellular product from subcutaneous fat. The adipose-derived stromal vascular fraction (SVF) is an early intervention and late-stage novel 'at point' of care cellular treatment, demonstrating improvements in clinical applications for Multiple Sclerosis, Alzheimer's disease, and Parkinson's disease. SVF is a heterogeneous fraction of cells forming a robust cellular ecosystem and serving as a novel and valuable source of point-of-care autologous cell therapy, providing an easy-to-access population that we hypothesize can mediate repair through 'bi-directional' communication in response to pathological cues. We provide the first comprehensive review of all pre-clinical and clinical findings available to date and highlight major challenges and future directions. There is a greater medical and economic urgency to innovate and develop novel cellular therapy solutions that enable the repair and regeneration of neuronal tissue that has undergone irreversible and permanent damage.
Assuntos
Tecido Adiposo , Doenças Neurodegenerativas , Animais , Humanos , Tecido Adiposo/irrigação sanguínea , Células Estromais/patologia , Sistemas Automatizados de Assistência Junto ao Leito , Doenças Neurodegenerativas/terapia , Doenças Neurodegenerativas/patologia , Ecossistema , Terapia Baseada em Transplante de Células e TecidosRESUMO
OBJECTIVE: The objective of the study is to demonstrate the innovation and utility of mesenteric tissue culture for discovering the microvascular growth dynamics associated with adipose-derived stromal vascular fraction (SVF) transplantation. Understanding how SVF cells contribute to de novo vessel growth (i.e., neovascularization) and host network angiogenesis motivates the need to make observations at single-cell and network levels within a tissue. METHODS: Stromal vascular fraction was isolated from the inguinal adipose of adult male Wistar rats, labeled with DiI, and seeded onto adult Wistar rat mesentery tissues. Tissues were then cultured in MEM + 10% FBS for 3 days and labeled for BSI-lectin to identify vessels. Alternatively, SVF and tissues from green fluorescent-positive (GFP) Sprague Dawley rats were used to track SVF derived versus host vasculature. RESULTS: Stromal vascular fraction-treated tissues displayed a dramatically increased vascularized area compared to untreated tissues. DiI and GFP+ tracking of SVF identified neovascularization involving initial segment formation, radial outgrowth from central hub-like structures, and connection of segments. Neovascularization was also supported by the formation of segments in previously avascular areas. New segments characteristic of SVF neovessels contained endothelial cells and pericytes. Additionally, a subset of SVF cells displayed the ability to associate with host vessels and the presence of SVF increased host network angiogenesis. CONCLUSIONS: The results showcase the use of the rat mesentery culture model as a novel tool for elucidating SVF cell transplant dynamics and highlight the impact of model selection for visualization.
Assuntos
Células Endoteliais , Células Estromais , Ratos , Masculino , Animais , Fração Vascular Estromal , Ratos Sprague-Dawley , Ratos Wistar , Microvasos , Tecido Adiposo/irrigação sanguínea , Neovascularização Patológica , MesentérioRESUMO
BACKGROUND: Cortisol and corticosterone both circulate in human plasma and, due to differing export by ATP-binding cassette (ABC) transporters, may exert differential cellular effects. ABCB1 (expressed in brain) exports cortisol not corticosterone while ABCC1 (expressed in adipose and skeletal muscle) exports corticosterone not cortisol. We hypothesised that ABCC1 inhibition increases corticosteroid receptor occupancy by corticosterone but not cortisol in humans. METHODS: A randomised double-blind crossover study was conducted in 14 healthy men comparing placebo and ABCC1 inhibitor probenecid. Blood sampling, including from veins draining adipose and muscle, was undertaken before and after administration of mineralocorticoid receptor antagonist potassium canrenoate and glucocorticoid receptor antagonist mifepristone (RU486). RESULTS: During placebo, systemic plasma cortisol and corticosterone concentrations increased promptly after canrenoate. Cortisol uptake was detected from adipose but not muscle following canrenoateâ¯+â¯RU486. Probenecid significantly increased systemic cortisol concentrations, and tended to increase corticosterone and ACTH concentrations, after combined receptor antagonism but had no effects on net glucocorticoid balance in either adipose or muscle. Using quantitative PCR in brain bank tissue, ABCC1 expression was 5-fold higher in human pituitary than hypothalamus and hippocampus. ABCB1 was more highly expressed in hypothalamus compared to pituitary. CONCLUSIONS: Although displacement of corticosterone and/or cortisol from receptors in adipose and skeletal muscle could not be measured with sufficient precision to detect effects of probenecid, ABCC1 inhibition induced a greater incremental activation of the hypothalamic-pituitary-adrenal axis after combined receptor blockade, consistent with ABCC1 exporting corticosterone from the pituitary and adding to the evidence that ABC transporters modulate tissue glucocorticoid sensitivity.
Assuntos
Sistema Hipotálamo-Hipofisário/fisiologia , Proteínas Associadas à Resistência a Múltiplos Medicamentos/fisiologia , Sistema Hipófise-Suprarrenal/fisiologia , Subfamília B de Transportador de Cassetes de Ligação de ATP/fisiologia , Tecido Adiposo/irrigação sanguínea , Tecido Adiposo/metabolismo , Hormônio Adrenocorticotrópico/sangue , Adulto , Estudos Cross-Over , Método Duplo-Cego , Humanos , Masculino , Proteínas Associadas à Resistência a Múltiplos Medicamentos/antagonistas & inibidores , Proteínas Associadas à Resistência a Múltiplos Medicamentos/genética , Músculo Esquelético/metabolismoRESUMO
Adipose tissue depots are invested with an extensive capillary network that is closely associated with maintenance of adipose functions and enables healthy tissue expansion. The capillary network displays a high level of plasticity, demonstrating either growth (angiogenesis) or regression (rarefaction) under various physiological/pathological conditions, which has significant consequences for cardiometabolic health. Thus, the visualization and quantification of adipose vascular networks is an important aspect of studying factors that regulate adipose tissue health. This chapter provides an overview of several methods to quantify adipose vascularization. In-depth protocols are provided for the visualization of vascular structures by staining and imaging of whole-mount adipose tissues or paraffin-embedded adipose tissue sections, together with the quantitative analysis of vascularization from these images.
Assuntos
Tecido Adiposo , Neovascularização Patológica , Tecido Adiposo/irrigação sanguínea , Humanos , Neovascularização Fisiológica , Coloração e RotulagemAssuntos
Tecido Adiposo/irrigação sanguínea , Arteríolas/virologia , COVID-19/virologia , Vasos Coronários/virologia , SARS-CoV-2/patogenicidade , Vasodilatação , Acetilcolina/farmacologia , Adulto , Arteríolas/efeitos dos fármacos , Arteríolas/fisiopatologia , Apêndice Atrial , COVID-19/diagnóstico , COVID-19/fisiopatologia , Estudos de Casos e Controles , Vasos Coronários/efeitos dos fármacos , Vasos Coronários/fisiopatologia , Feminino , Interações Hospedeiro-Patógeno , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Tempo , Vasodilatação/efeitos dos fármacos , Vasodilatadores/farmacologiaRESUMO
Adipose tissue-derived microvascular fragments (MVF) are functional vessel segments, which rapidly reassemble into new microvasculatures under experimental in vitro and in vivo conditions. Accordingly, they have been used for many years in microcirculation research to study basic mechanisms of endothelial cell function, angiogenesis, and microvascular network formation in two- and three-dimensional environments. Moreover, they serve as vascularization units for musculoskeletal regeneration and implanted biomaterials as well as for the treatment of myocardial infarction and the generation of prevascularized tissue organoids. Besides, multiple factors determining the vascularization capacity of MVF have been identified, including their tissue origin and cellular composition, the conditions for their short- and long-term storage, as well as their implantation site and the general health status and medication of the recipient. The next challenging step is now the successful translation of all these promising experimental findings into clinical practice. If this succeeds, a multitude of future therapeutic applications may significantly benefit from the remarkable properties of MVF. Impact Statement The present review provides a complete overview of the broad application spectrum of adipose tissue-derived microvascular fragments (MVF) in angiogenesis research and regenerative medicine. Moreover, it systematically describes factors determining their vascularization capacity. These factors may be used to further improve the remarkable properties of MVF in personalized medicine and to promote their rapid introduction as vascularization units into clinical practice.
Assuntos
Neovascularização Fisiológica , Medicina Regenerativa , Humanos , Microcirculação , Microvasos , Tecido Adiposo/irrigação sanguínea , Materiais Biocompatíveis , Engenharia TecidualRESUMO
The perivascular adipose tissue (PVAT) refers to an ectopic local deposit of connective tissue that anatomically surrounds most of the blood vessels. While it was initially known only as a structural support for vasculature, the landmark findings of Soltis and Cassis (1991), first demonstrating that PVAT reduces the contractions of norepinephrine in the isolated rat aorta, brought the potential vascular role of PVAT into the limelight. This seminal work implied the potential ability of PVAT to influence vascular responsiveness. Several vasoactive/vasocrine substances influencing vascular homeostasis were successively shown to be released from PVAT that include both adipocyte-derived relaxing and contracting factors. The PVAT is currently recognized as a metabolically active endocrine organ and is eventually considered as the 'protagonist' in vascular homeostasis. It plays prominent defending and opposing roles in vascular function, while the actual vascular influences of PVAT vary with an increase in adiposity. Recent studies have presented compelling evidence implicating the pivotal role of PVAT in the local activation of the renin-angiotensin system (RAS), which substantially impacts vascular physiology and physiopathology. Current findings have advanced our understanding of the role of PVAT in favorably or adversely modulating the vascular function through differential RAS activation. Given that adipocytes also produce major RAS components locally to influence vascular function, this review provides a scientific basis to distinctly understand the key role of PVAT in regulating the autocrine and paracrine functions of vascular RAS components and its potential as an emerging therapeutic target for mitigating cardiovascular complications.
Assuntos
Tecido Adiposo/irrigação sanguínea , Sistema Renina-Angiotensina , Tecido Adiposo/fisiologia , Animais , HumanosRESUMO
Investigations into the mechanisms regulating obesity are frantic and novel translational approaches are needed. The raccoon dog (Nyctereutes procyonoides) is a canid species representing a promising model to study metabolic regulation in a species undergoing cycles of seasonal obesity and fasting. To understand the molecular mechanisms of metabolic regulation in seasonal adaptation, we analyzed key central nervous system and peripheral signals regulating food intake and metabolism from raccoon dogs after autumnal fattening and winter fasting. Expressions of neuropeptide Y (NPY), orexin-2 receptor (OX2R), pro-opiomelanocortin (POMC) and leptin receptor (ObRb) were analyzed as examples of orexigenic and anorexigenic signals using qRT-PCR from raccoon dog hypothalamus samples. Plasma metabolic profiles were measured with 1H NMR-spectroscopy and LC-MS. Circulating hormones and cytokines were determined with canine specific antibody assays. Surprisingly, NPY and POMC were not affected by the winter fasting nor autumn fattening and the metabolic profiles showed a remarkable equilibrium, indicating conserved homeostasis. However, OX2R and ObRb expression changes suggested seasonal regulation. Circulating cytokine levels were not increased, demonstrating that the autumn fattening did not induce subacute inflammation. Thus, the raccoon dog developed seasonal regulatory mechanisms to accommodate the autumnal fattening and prolonged fasting making the species unique in coping with the extreme environmental challenges.
Assuntos
Adiposidade , Jejum/metabolismo , Metaboloma , Cães Guaxinins/metabolismo , Estações do Ano , Tecido Adiposo/irrigação sanguínea , Tecido Adiposo/patologia , Animais , Biomarcadores/metabolismo , Peso Corporal , Análise Discriminante , Feminino , Hormônios/sangue , Hipotálamo/metabolismo , Inflamação/patologia , Análise dos Mínimos Quadrados , Limite de Detecção , Análise Multivariada , Peptídeos/genética , Peptídeos/metabolismo , Espectroscopia de Prótons por Ressonância Magnética , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Cães Guaxinins/sangue , Receptores de Peptídeos/metabolismoRESUMO
Several studies have suggested that extracellular matrix (ECM) remodeling and the microenvironment are tightly associated with adipogenesis and adipose angiogenesis. In the present study, we demonstrated that transforming growth factor-beta induced (TGFBI) suppresses angiogenesis stimulated by adipocyte-conditioned medium (Ad-CM), both in vitro and in vivo. TGFBI knockout (KO) mice exhibited increased numbers of blood vessels in adipose tissue, and blood vessels from these mice showed enhanced infiltration into Matrigel containing Ad-CM. The treatment of Ad-CM-stimulated SVEC-10 endothelial cells with TGFBI protein reduced migration and tube-forming activity. TGFBI protein suppressed the activation of the Src and extracellular signaling-related kinase signaling pathways of these SVEC-10 endothelial cells. Our findings indicated that TGFBI inhibited adipose angiogenesis by suppressing the activation of Src and ERK signaling pathways, possibly because of the stimulation of the angiogenic activity of endothelial cells.
Assuntos
Tecido Adiposo/irrigação sanguínea , Endotélio Vascular/metabolismo , Proteínas da Matriz Extracelular/metabolismo , Neovascularização Fisiológica , Fator de Crescimento Transformador beta/metabolismo , Tecido Adiposo/metabolismo , Animais , Capilares/crescimento & desenvolvimento , Capilares/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos KnockoutRESUMO
The purpose of present study was to longitudinally investigate the alterations in infrapatellar fat pad (IPFP) vascularity in 5/6 nephrectomized rats by using dynamic contrast enhanced (DCE) MRI and IPFP degeneration by using MRI T2* relaxation time. Twelve male Sprague-Dawley rats were assigned to a control group and a 5/6 nephrectomy CKD group. The right knees of all rats were longitudinally scanned by 4.7 T MRI, and serial changes in the IPFP were assessed at 0, 8, 16, 30, and 44 weeks by DCE-MRI (parameters A, kel and kep) and MRI T2* mapping. After MRI measurements, knee specimens were obtained and evaluated histologically. The CKD group had IPFPs with lower blood volume A and lower permeability kep values from 16 weeks (p < 0.05), lower venous washout kel value from 30 weeks (p < 0.001), and significantly higher T2* values reflecting adipocyte degeneration beginning at 16 weeks (p < 0.05). The histopathological results confirmed the MRI findings. Hypoperfusion and adipocytes degeneration related to CKD were demonstrated in a rodent 5/6 nephrectomy model. DCE parameters and MRI T2* can serve as imaging biomarkers of fat pad degeneration during CKD progression.
Assuntos
Tecido Adiposo/patologia , Rim/patologia , Articulação do Joelho/patologia , Insuficiência Renal Crônica/patologia , Tecido Adiposo/irrigação sanguínea , Animais , Progressão da Doença , Articulação do Joelho/irrigação sanguínea , Imageamento por Ressonância Magnética , Masculino , Nefrectomia , Ratos , Ratos Sprague-Dawley , Insuficiência Renal Crônica/etiologiaRESUMO
BACKGROUND/OBJECTIVES: Ghrelin is an orexigenic hormone that increases food intake, adiposity, and insulin resistance through its receptor Growth Hormone Secretagogue Receptor (GHS-R). We previously showed that ghrelin/GHS-R signaling has important roles in regulation of energy homeostasis, and global deletion of GHS-R reduces obesity and improves insulin sensitivity by increasing thermogenesis. However, it is unknown whether GHS-R regulates thermogenic activation in adipose tissues directly. METHODS: We generated a novel adipose tissue-specific GHS-R deletion mouse model and characterized the mice under regular diet (RD) and high-fat diet (HFD) feeding. Body composition was measured by Echo MRI. Metabolic profiling was determined by indirect calorimetry. Response to environmental stress was assessed using a TH-8 temperature monitoring system. Insulin sensitivity was evaluated by glucose and insulin tolerance tests. Tissue histology was analyzed by hematoxylin/eosin and immunofluorescent staining. Expression of genes involved in thermogenesis, angiogenesis and fibrosis in adipose tissues were analyzed by real-time PCR. RESULTS: Under RD feeding, adipose tissue-specific GHS-R deletion had little or no impact on metabolic parameters. However, under HFD feeding, adipose tissue-specific GHS-R deletion attenuated diet-induced obesity and insulin resistance, showing elevated physical activity and heat production. In addition, adipose tissue-specific GHS-R deletion increased expression of master adipose transcription regulator of peroxisome proliferator-activated receptor (PPAR) γ1 and adipokines of adiponectin and fibroblast growth factor (FGF) 21; and differentially modulated angiogenesis and fibrosis evident in both gene expression and histological analysis. CONCLUSIONS: These results show that GHS-R has cell-autonomous effects in adipocytes, and suppression of GHS-R in adipose tissues protects against diet-induced obesity and insulin resistance by modulating adipose angiogenesis and fibrosis. These findings suggest adipose GHS-R may constitute a novel therapeutic target for treatment of obesity and metabolic syndrome.