脂肪细胞因子与糖尿病心肌病变

糖尿病心肌病变在病理上主要表现为心肌间质重构和心肌纤维化,其具体发病机制尚不明确,与糖代谢障碍、心肌微血管病变等有关.新近研究发现脂肪组织可分泌多种生物活性物质如apelin、网膜素、visfatin、chemerin等,这些脂肪因子可能通过影响肾素-血管紧张素系统、心肌胰岛素抵抗、心肌能量代谢及心肌血管内皮功能等途径直接或间接影响心肌纤维化过程,进而对糖尿病心肌病变产生作用.     

心外膜脂肪组织的超声学评估方法及临床应用

<正>心外膜脂肪组织(epicardial adipose tissue,EAT)是位于心肌与脏层心包之间的脂肪组织,其解剖位置与心肌、冠状动脉紧密相连,可释放多种促炎因子。研究显示,EAT与多种心血管及代谢性疾病相关。近年来,EAT超声学评估方法受到广泛采纳,被用于心血管及代谢性疾病的临床研究。1 EAT特点EAT属于内脏脂肪组织,与其他内脏脂肪组织(如肠系膜脂肪、网膜脂肪等)共同来源于消化道相关的内脏中胚层,     

心外膜脂肪与心房颤动的研究进展

心外膜脂肪是位于心肌与脏层心包之间的特殊内脏脂肪组织。心外膜脂肪作为身体脂肪的一个贮存库,与心房颤动的发生、严重程度以及射频消融的结局密切相关。心外膜脂肪可能通过脂肪浸润、促纤维化和炎性反应等多种机制影响心房颤动的发生和发展。近年研究发现,通过B超、CT和磁共振成像(MRI)等技术检测心外膜脂肪的厚度或容积可以预测心房颤动的发生、相关并发症和射频消融的结局。     

心外膜脂肪组织与心血管疾病的研究进展

脂肪组织包括内脏脂肪组织和皮下脂肪组织, 其中内脏脂肪组织异常沉积引起的心血管事件的发生率和病死率较高。心外膜脂肪组织归类为内脏脂肪组织, 尽管重量仅占全身脂肪组织的0.02%, 但因解剖位置和生物学功能特殊, 其在冠心病、心房颤动、心力衰竭、新型冠状病毒肺炎相关的心肌损伤、高血压等心血管疾病的发生和发展中发挥着重要作用。该文主要就心外膜脂肪的解剖与生物学功能、影像学评估及其与心血管疾病的关系进行了综述。     

心外膜脂肪组织在心力衰竭中的研究进展

心外膜脂肪组织(EAT)是位于心肌表面的内脏脂肪库,有研究表明EAT可通过多种机制介导心力衰竭的发生和发展。现主要概述EAT的解剖和生理功能、在心力衰竭中的作用和发病机制,以及将EAT作为治疗靶点的治疗方法。     

白细胞介素与心肌纤维化关系研究进展

心血管疾病已成为全球关注的健康问题,其发病率和病死率呈逐年上升趋势,而心血管疾病导致的心力衰竭与心肌纤维化有着密切的联系。因此,研究心肌纤维化的发病机制有助于预防心血管疾病的发生、发展。心肌纤维化发病机制比较复杂,其中氧化应激和炎症发挥重要作用,作为炎症因子之一的白细胞介素可通过多方面影响心肌纤维化,本文将重点介绍白细胞介素与心肌纤维化关系的研究进展。     

心肌纤维化的信号传导机制及中医药治疗探讨

心肌纤维化是心力衰竭发展的重要机制,是心力衰竭病人预后不良的主要原因。心肌纤维化的形成过程涉及多种信号传导机制,可划分为促进心肌纤维化形成的信号传导机制[肾素-血管紧张素-醛固酮系统、转化生长因子β_1(TGF-β_1)/信号转导蛋白(Smads)、炎症反应、氧化应激反应]和抑制心肌纤维化形成的信号传导机制(gp130-JAKs-STAT3信号通路),通过对信号传导机制的进一步研究,可加深对心肌纤维化的理解,为临床治疗心肌纤维化提供新的靶标。中医药治疗心肌纤维化具有"标本同治"的优势,研究证实多种中药复方和单味药均不同程度的抑制心肌纤维化,但其对心肌纤维化信号传导机制的研究尚存在不足,值得进一步探讨。     

可溶性基质裂解素2与心肌纤维化相关性的研究进展

心肌纤维化可导致心力衰竭、冠心病、心肌病、高血压、心房颤动等多种心血管疾病的发生。多项研究表明可溶性基质裂解素2(sST2)是心肌纤维化的新型标志物,参与心肌纤维化过程,与各种心血管疾病的发生、发展及不良预后密切相关。现对sST2的生物学特性、作用机制及与心肌纤维化相关的心血管疾病进行阐述。     

基于氧化应激探究中医药防治心肌纤维化的研究进展

心肌纤维化是多数心血管疾病的共同病理机制,其持续性进展将导致心力衰竭和死亡等不良临床预后。近年来,心肌纤维化的机制研究越来越受到中外学者的重视,而氧化应激为心肌纤维化领域的热点话题。心肌组织受到外界影响因子刺激后,活性氧增加,诱导成纤维细胞增殖或通过促进细胞外基质合成,诱发心肌纤维化。中医药在抑制心肌纤维化方面具有多途径、多靶标的优势。本研究以氧化应激为切入点,综述以氧化应激为靶标的中医药防治心肌纤维化的研究进展。     

MicroRNA133a在心肌纤维化中的作用机制及最新进展

MicroRNAs是一类内源性非编码RNA分子,参与细胞生长、增殖和分化,在多种心血管病的进展过程中起着重要的调节作用。MicroRNA133a可通过直接抑制下游靶基因表达和调控相关信号通路参与复杂的心肌纤维化过程,不仅被认为是诊断性生物标志物,而且也被认为对心脏纤维化有潜在的治疗作用。现介绍microRNA133a及其信号通路在心肌纤维化中的作用机制,并将其在心肌纤维化中的治疗应用前景做一综述。     

Adipose tissue as an endocrine organ? A review of recent data related to cardiovascular complications of endocrine dysfunctions

Clinical and experimental data obtained in the last few years have modified the concept of adipose tissue as one solely directed at energy storage and release. The adipose tissue is a target organ for glucocorticoids and several studies have been carried out on the function of hypothalamic-pituitary-adrenal axis in obese subjects without conclusive results. A recent and innovative finding is that adipose tissue can produce cortisol from its inactive precursor, cortisone. The identification of leptin, a hormone synthesised by fat tissue, has ushered in the modern view of this tissue as a true endocrine organ. Leptin is produced primarily by subcutaneous and to a lesser extent by visceral adipose tissue, and has a central role in controlling body weight and, especially in regulating fat stores. Leptin is also involved in several complex functions, including physiological processes associated with puberty. Another hormone of fat tissue is angiotensinogen, which is produced in larger amounts by visceral than subcutaneous fat. Human and animals adipose tissue express a whole renin-angiotensin system (RAS). Angiotensin II, the final effector of this system is probably produced locally by adipose tissue. The function of adipose RAS is not well known. RAS can participate together with other hormones and substances, in adipocyte differentiation and fat tissue growth, but could be also involved in the pathogenesis of complications of obesity including arterial hypertension.     

WILLENDORF AWARDAW0001Establishment of the concept of visceral fat syndrome and the discovery of adiponectin

Clinical studies in recent years have demonstrated that the extent of obesity does not necessarily determine the development of obesity‐related diseases such as type2 diabetes, hyperlipidemia, hypertension, but fat distribution is a much more important determinant In 1983, we reported a method for fat analysis using CT scan which enabled us to analyze in intraabdominal adipose tissue, namely visceral fat as well as subcutaneous fat. Then we demonstrated that visceral fat accumulation correlated to the disturbance of lipid and glucose metabolism, insulin resistance, hypertension and cardiovascular disease in obese subjects and even in non‐obese subjects. From these clinical studies, we proposed the concept of ‘visceral fat syndrome’ in which multiple risk factors cluster through visceral fat accumulation. Besides, this syndrome is designated to be a very atherogenic state. Visceral fat syndrome is corresponding to the concept of metabolic syndrome recently noted. In order to clarify the molecular mechanism why visceral fat accumulation correlates to plural common diseases and also directly to atherosclerosis, we started a project for the analysis of adipose tissue using random sequence of expressed genes in adipose tissues. We found unexpectedly that adipose tissue, especially visceral fat, expressed strongly the genes encoding secretory proteins most of which are important bioactive substances (named as adipocytokines). In addition to known adipocytokines, several novel adipose‐specific genes were identified. Among them, a collagen‐like protein encoded by an adipose most abundant gene (apM‐1) is the most important novel adipocytokine which is named adiponectin. Adiponectin has anti‐diabetic, anti‐atherogenic, anti‐oncogenic and anti‐inflammatory properties and its plasma levels decreases with visceral fat accumulation, suggesting that this molecules may play a central role in the visceral fat syndrome or metabolic syndrome. In this lecture, I would like to present the importance of adiponectin together with other adipocytokines in lifestyle‐related diseases relevant to visceral fat accumulation.     

Adipose Tissue as an Endocrine Organ? A Review of Recent Data Related to Cardiovascular Complications of Endocrine Dysfunctions

Clinical and experimental data obtained in the last few years have modified the concept of adipose tissue as one solely directed at energy storage and release. The adipose tissue is a target organ for glucocorticoids and several studies have been carried out on the function of hypothalamic‐pituitary‐adrenal axis in obese subjects without conclusive results. A recent and innovative finding is that adipose tissue can produce cortisol from its inactive precursor, cortisone. The identification of leptin, a hormone synthesised by fat tissue, has ushered in the modern view of this tissue as a true endocrine organ. Leptin is produced primarily by subcutaneous and to a lesser extent by visceral adipose tissue, and has a central role in controlling body weight and, especially in regulating fat stores. Leptin is also involved in several complex functions, including physiological processes associated with puberty. Another hormone of fat tissue is angiotensinogen, which is produced in larger amounts by visceral than subcutaneous fat. Human and animals adipose tissue express a whole renin‐angiotensin system (RAS). Angiotensin II, the final effector of this system is probably produced locally by adipose tissue. The function of adipose RAS is not well known. RAS can participate together with other hormones and substances, in adipocyte differentiation and fat tissue growth, but could be also involved in the pathogenesis of complications of obesity including arterial hypertension.     

Potentialités et intérêt du tissu adipeux dans la sclérodermie

Systemic sclerosis is a disorder involving the connective tissue, arterioles and microvessels. It is characterized by skin and visceral fibrosis and ischemic phenomena. Currently, therapy is limited and no antifibrotic treatment has proven its efficacy. Beyond some severe organ lesions (pulmonary arterial hypertension, pulmonary fibrosis, scleroderma renal crisis), which only concern a minority of patients, the skin sclerosis of hands and face and the vasculopathy lead to physical and psychological disability in most patients. Thus, functional improvement of hand motion and face represents a priority for patient therapy. Due to its easy obtention by fat lipopaspirate and adipocytes survival, re injection of adipose tissue is a common therapy used in plastic surgery for its voluming effect. Identification and characterization of the adipose tissue-derived stroma vascular fraction, mainly including mesenchymal stem cells, have revolutionized the science showing that adipose tissue is a valuable source of multipotent stem cells, able to migrate to site of injury and to differentiate according to the receiver tissue's needs. Due to easy harvest by liposuction, its abundance in mesenchymal cells far higher that the bone marrow, and stroma vascular fraction's ability to differentiate and secrete growth angiogenic and antiapoptotic factors, the use of adipose tissue is becoming more attractive in regenerative medicine. We here present the interest of adipose tissue use in the treatment of the hands and face in scleroderma.     

Relationship between C-reactive protein and visceral adipose tissue in healthy Japanese subjects

AIM: Recent studies have suggested that the elevated C-reactive protein (CRP) levels are associated with body fat, especially visceral adipose tissue, but most of them were investigated in Westerners who had higher body mass index (BMI) than Asians. To investigate the association between CRP concentrations, parameters of visceral obesity, the insulin resistance syndrome and carotid atherosclerosis in healthy Japanese who had a lower BMI than Westerners. METHODS: We explored the relationships between fatness and visceral obesity parameters [by anthropometry, bioelectrical impedance analysis and abdominal computed tomography (CT)] and CRP (high sensitivity) and examined their associations with components of insulin resistance syndrome, interleukin-6 (IL-6), tissue necrosis factor-alpha (TNF-alpha) and intima-media thickness (IMT) of common carotid arteries (CCAs) by ultrasonograms in 116 healthy Japanese subjects. RESULTS: In crude regression analyses, CRP was significantly associated with measures of obesity. After adjustment for age, gender and smoking, the association with CRP was stronger for parameters of visceral obesity (waist circumference, waist-to-hip ratio and visceral adipose tissue accumulation) than for other parameters of obesity. IL-6 and TNF-alpha were not associated with CRP. Blood pressure (BP), metabolic variables and CCA-IMT were also significantly associated with CRP. But, after being adjusted for age, gender, smoking and BMI, BP and high-density lipoprotein cholesterol (HDLc) were significantly associated. CONCLUSION: CRP level is associated with visceral adipose tissue and is significantly associated with the components of insulin resistance syndrome in healthy Japanese subjects. These data support a possible role of visceral adipose tissue in inflammation component of atherosclerosis, and further studies are needed to study the mechanism of CRP elevation caused by visceral adipose tissue.     

血管周围脂肪组织与心肺血管疾病的研究进展

血管周围脂肪组织（perivascular adipose tissue, PVAT）是包绕在血管外膜的脂肪组织,与心肺血管疾病密切相关。在生理条件下,血管周围脂肪组织通过分泌血管活性物质调节血管张力;在病理条件下,失功能的血管周围脂肪组织通过分泌大量炎症因子、抗血管舒张因子、脂肪因子等参与高血压、动脉粥样硬化、肺动脉高压等疾病的进展。我们的既往研究还发现：失功能PVAT增加动脉粥样斑块易损性。心外膜脂肪（EAT）是位于心肌与脏层心包之间的脂肪组织,是血管周围脂肪组织的一种特殊类型,与心房颤动的发生和预后密切相关。本文拟对血管周围脂肪组织的结构特征和功能及其对心血管疾病的影响和作用机制进行综述。     

Hepatitis C virus directly associates with insulin resistance independent of the visceral fat area in nonobese and nondiabetic patients

Insulin resistance (IR) is known to be associated with the visceral adipose tissue area. Elucidation of the relationship between hepatitis C virus (HCV) and IR is of great clinical relevance, because IR promotes liver fibrosis. In this study, we tested the hypothesis that HCV infection by itself may promote IR. We prospectively evaluated 47 patients with chronic HCV infection who underwent liver biopsy. Patients with obesity, type 2 diabetes mellitus (DM), or a history of alcohol consumption were excluded. IR was estimated by calculation of the modified homeostasis model of insulin resistance (HOMA-IR) index. Abdominal fat distribution was determined by computed tomography. Fasting blood glucose levels were within normal range in all the patients. The results of univariate analysis revealed a significant correlation between the quantity of HCV-RNA and the HOMA-IR (r = 0.368, P = 0.0291). While a significant correlation between the visceral adipose tissue area and the HOMA-IR was also observed in the 97 control, nondiabetic, non-HCV-infected patients (r = 0.398, P < 0.0001), no such significant correlation between the visceral adipose tissue area and the HOMA-IR (r = 0.124, P = 0.496) was observed in the patients with HCV infection. Multiple regression analysis with adjustment for age, gender and visceral adipose tissue area revealed a significant correlation between the HCV-RNA and the HOMA-IR (P = 0.0446). HCV is directly associated with IR in a dose-dependent manner, independent of the visceral adipose tissue area. This is the first report to demonstrate the direct involvement of HCV and IR in patients with chronic HCV infection.     

Contribution of CB1 blockade to the management of high-risk abdominal obesity

The worldwide increase in the prevalence of type 2 diabetes represents a tremendous challenge for our healthcare system, especially if we consider that this phenomenon is largely explained by the epidemic of obesity. However, despite the well-recognized increased morbidity and mortality associated with an elevated body weight, there is now more and more evidence highlighting that abdominal adipose tissue is the fat depot that conveys the greatest risk of metabolic complications. This cluster of metabolic abnormalities has been referred to as the metabolic syndrome and this condition is largely the consequence of abdominal obesity, especially when accompanied by a high accumulation of visceral adipose tissue. This cluster of metabolic complications has also been found to be predictive of a substantially increased risk of coronary heart disease beyond the presence of traditional risk factors. Moreover, a moderate weight loss in initially abdominally obese patients is associated with a selective mobilization of visceral adipose tissue, leading to improvements in the metabolic risk profile predictive of a reduced risk of coronary heart disease and of type 2 diabetes. The recent discovery of the endocannabinoid-CB1 receptor system and of its impact on the regulation of energy metabolism represents a significant advance, which will help physicians target abdominal obesity and its related metabolic complications. In this regard, studies have shown that rimonabant therapy (the first developed CB1 blocker) could be useful for the management of clustering cardiovascular disease risk factors in high-risk abdominally obese patients through its effects not only on energy balance but also on adipose tissue metabolism. For instance, the presence of CB1 receptors in adipose tissue and the recently reported effect of rimonabant on adiponectin production by adipose cells may represent a key factor responsible for the weight loss-independent effect of this CB1 blocker on cardiometabolic risk variables.     

Visceral Adipose Tissue and Cardiovascular Disease Risk

Adipose tissue has been recognized as an endocrine organ. Cytokines released from adipose tissue not only influence lipid metabolism, they also affect multiple organ systems such as the immune and nervous systems, and of interest in this review, the cardiovascular system. While there are multiple depots of adipose tissue, visceral adipose tissue appears to be the most metabolically active. This fat depot has been linked to dysfunction of the vascular endothelium with the subsequent development of atherosclerosis and incident cardiovascular events. In this regard and within the last two years, several studies have examined the effect of visceral adipose tissue on subclinical and clinical CVD outcomes. This review highlights these findings and focuses on the associations between visceral adipose tissue and ethnicity, risk factors, vascular changes, clinical effects and cardiovascular disease outcomes.