肥胖与高密度脂蛋白代谢异常研究进展

肥胖是代谢综合征发生发展的中心环节,其与代谢综合征的各个危险因素密切相关.高密度脂蛋白胆固醇水平降低是代谢综合征的特征性血脂代谢异常之一.有研究表明肥胖可通过多种途径影响体内高密度脂蛋白水平和功能,如高甘油三酯血症,脂肪细胞因子,炎症状态,载脂蛋白M异常等.而高密度脂蛋白胆固醇水平降低及功能异常是动脉粥样硬化进展的独立危险因素.本文就肥胖与高密度脂蛋白异常及其影响因素的研究进展作一综述.     

高同型半胱氨酸血症与脂肪功能异常

近年来,2型糖尿病、肥胖的发病率在我国急剧增加,并且趋于年轻化,已经成为严重威胁人民健康的重要疾病.脂肪功能异常出现于肥胖的早期阶段,是肥胖患者发生代谢异常及心脑血管疾病的重要机制[1-2].高同型半胱氨酸血症作为动脉粥样硬化的独立危险因素,在我国的发病率处于较高水平[3].研究显示,同型半胱氨酸（Hcy）可通过多条途径导致脂肪功能异常,进而引发机体慢性炎症状态及胰岛素抵抗[4-5].现就同型半胱氨酸与脂肪功能异常的相关机制及最新研究进展作一阐述.     

脂肪因子与肥胖相关心血管疾病关系的研究进展

肥胖是各种心血管疾病（包括高血压、动脉粥样硬化和心肌梗死）的危险因素。通过对脂肪组织微环境以及对全身代谢影响的研究,可揭示肥胖相关心血管疾病的发病机制。脂肪组织具有分泌多种免疫调节蛋白的功能,这些免疫调节蛋白称为脂肪因子。肥胖可导致促炎性脂肪因子的表达增加和抗炎性脂肪因子的表达减少,从而产生一种慢性轻度的炎症状态。这种脂肪因子的失衡被认为是促进全身代谢功能障碍和心血管疾病的关键原因。     

载脂蛋白B48研究进展

载脂蛋白B48主要由小肠合成,参与乳糜微粒的组装、代谢,是食物脂肪吸收中不可缺少的蛋白.其表达量受多种因素影响.异常表达可导致小肠脂代谢异常,进而导致肥胖发生和动脉粥样硬化等疾病.本文主要针对载脂蛋白B48相关研究进行综述.     

内脏脂肪素与冠状动脉性心脏病的研究进展

内脏脂肪素是新近发现的脂肪细胞分泌的特异性蛋白质,循环血液中含量较丰富。内脏脂肪素通过促炎症反应和致动脉粥样硬化形成在冠心病的发生和发展中起重要作用,在冠状动脉性心脏病的危险因素如肥胖、2型糖尿病及胰岛素抵抗中也起到重要作用。它为深入研究冠状动脉心脏病发病机制提供了一个新的思路。     

脂肪因子与冠状动脉粥样硬化关系的研究进展

肥胖是由于脂肪组织增多导致体质量增加的病理状态,并可导致2型糖尿病、高血压等一系列疾病的发生风险增高.同时,肥胖也是冠心病的独立危险因素,已有研究证实胰岛素抵抗、糖代谢异常、脂质代谢异常、内皮功能障碍等是导致冠心病发生的可能机制.脂肪组织是机体最大的内分泌器官,能分泌多种脂肪因子,越来越多的研究揭示瘦素、脂联素等脂肪因子在冠心病的发生过程中发挥着重要作用.近几年发现了众多的脂肪因子,如内脂素、视黄醇结合蛋白4、爱帕琳肽、趋化素、网膜素、二肽基肽酶4、C1q/肿瘤坏死因子相关蛋白9和人分泌型卷曲相关蛋白5等,可能和冠状动脉粥样硬化关系密切,深入研究这些脂肪因子在冠心病中的作用以及相关机制,能为肥胖相关冠心病的治疗寻找新的靶点.我们主要对新近发现的脂肪因子和冠状动脉粥样硬化关系的研究进展进行综述.     

动脉粥样硬化危险因素衰老、肥胖、生物钟紊乱与核糖体新生的研究进展

动脉粥样硬化是心脑血管疾病的主要原因,可能由吸烟、高血压、衰老、肥胖、生物钟紊乱等多因素导致。核糖体作为蛋白质合成的分子机器,维持细胞内蛋白质稳态。文章聚焦于衰老、肥胖和生物钟紊乱对动脉粥样硬化的影响,以及与核糖体新生的关系,为动脉粥样硬化的机制研究和防治提供理论支持。     

三酰甘油脂肪酶与动脉粥样硬化的研究进展

<正>肥胖是当今影响人类健康的重要疾病,肥胖患者易发生动脉粥样硬化,从而引起心脑血管疾病。肥胖与动脉粥样硬化密切相关,而脂肪组织分泌的细胞因子在二者中起到重要作用。因此,识别新型脂肪因子在调节动脉粥样硬化的过程中的作用,可能会提供新的思路来发现更为有效的预防心血管疾病的方法。脂肪组织分泌的多种细胞因子参与体内的炎症反应,引起代谢紊乱从而引起动脉粥样硬化,如脂联素、瘦素、肿瘤坏死因子α(TNF-α)、内脏     

瘦素与糖尿病动脉粥样硬化

瘦素是由脂肪细胞分泌的激素,其作用有利于维持体重、体脂的稳定,并可影响血糖水平。瘦素与糖尿病大血管病变发生发展的一系列危险因素如肥胖、高血压、糖、脂代谢紊乱等相关,提示瘦素与糖尿病动脉粥样硬化有关。瘦素通过引起内皮功能紊乱、内皮细胞增殖和血管形成、诱导氧化应激、增加泡沫细胞形成、促进血小板聚集和促进血管平滑肌细胞迁移及增殖等机制参与动脉粥样硬化的形成。     

残粒脂蛋白经脂肪细胞发挥致动脉粥样硬化作用

残粒脂蛋白被认为是致动脉粥样硬化的脂蛋白.脂肪细胞分泌的各种促炎脂肪因子在动脉粥样硬化发生、发展的慢性炎症反应中起重要作用.肥胖是冠心病和动脉粥样硬化的一个独立危险因素.残粒脂蛋白通过刺激促炎脂肪因子的释放、诱导前体脂肪细胞向成熟脂肪细胞的成脂分化,从而促进动脉粥样硬化的发生发展.此外,脂肪细胞对残粒脂蛋白代谢的调节也可能影响残粒脂蛋白在体内致动脉粥样硬化作用的强度.     

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.     

Human epicardial adipose tissue: a review

We discuss the anatomy, physiology, and pathophysiology of epicardial adipose tissue and its relationship to coronary atherosclerosis. Epicardial fat stores triglyceride to supply free fatty acids for myocardial energy production and produces adipokines. It shares a common embryological origin with mesenteric and omental fat. Like visceral abdominal fat, epicardial fat thickness, measured by echocardiography, is increased in obesity. Epicardial fat could influence coronary atherogenesis and myocardial function because there is no fibrous fascial layer to impede diffusion of free fatty acids and adipokines between it and the underlying vessel wall as well as the myocardium. Segments of coronary arteries lacking epicardial fat or separated from it by a bridge of myocardial tissue are protected against the development of atherosclerosis in those segments. However, when epicardial fat is totally absent in congenital generalized lipodystrophy, coronary atherosclerosis can still occur. Macrophages are more numerous and densely packed in the periadventitial fat of human atherosclerotic coronary arteries with lipid cores than in that of fibrocalcific or nonatherosclerotic coronary arteries. In obese patients with multiple cardiovascular risk factors, epicardial fat around atheromatous coronaries secretes several proinflammatory cytokines and is infiltrated by macrophages, lymphocytes, and basophils. Epicardial adipokine expression in obesity without coronary atherosclerosis has not been determined. In nonobese patients, epicardial fat around atheromatous coronary arteries expresses proinflammatory cytokines but produces either less adiponectin, a vasoprotective adipokine, than fat around nonatheromatous coronaries or a similar amount compared with thoracic subcutaneous fat. Further studies should be done to test the hypothesis that adipokines produced by and released from human epicardial adipose tissue might contribute locally to the pathogenesis of coronary atherosclerosis.     

代谢炎症与肥胖相关研究进展

肥胖是能量代谢失衡所导致的体脂过度积聚,可引起动脉粥样硬化、胰岛素抵抗和血脂异常等多种代谢综合征的发生。肥胖本身是一种发生在脂肪组织的慢性炎症疾病,伴随着脂肪组织细胞内炎症信号通路的激活、炎性细胞因子的释放和免疫细胞的浸润等病理改变。脂肪组织释放的炎症介质也可进入循环系统而影响其他组织器官功能,引起相关代谢综合征的发生。因此,代谢炎症在肥胖中的发生机制是研究肥胖及其相关疾病的基础,针对肥胖代谢炎症的治疗方法和新靶点的开发也将为肥胖及其相关代谢疾病的治疗带来新的思路。     

Lipotoxicity plays a key role in the development of both insulin resistance and muscle atrophy in patients with type 2 diabetes

Insulin resistance and muscle mass loss often coincide in individuals with type 2 diabetes. Most patients with type 2 diabetes are overweight, and it is well established that obesity and derangements in lipid metabolism play an important role in the development of insulin resistance in these individuals. Specifically, increased adipose tissue mass and dysfunctional adipose tissue lead to systemic lipid overflow and to low‐grade inflammation via altered secretion of adipokines and cytokines. Furthermore, an increased flux of fatty acids from the adipose tissue may contribute to increased fat storage in the liver and in skeletal muscle, resulting in an altered secretion of hepatokines, mitochondrial dysfunction, and impaired insulin signalling in skeletal muscle. Recent studies suggest that obesity and lipid derangements in adipose tissue can also lead to the development of muscle atrophy, which would make insulin resistance and muscle atrophy two sides of the same coin. Unfortunately, the exact relationship between lipid accumulation, type 2 diabetes, and muscle atrophy remains largely unexplored. The aim of this review is to discuss the relationship between type 2 diabetes and muscle loss and to discuss some of the joint pathways through which lipid accumulation in organs may affect peripheral insulin sensitivity and muscle mass.     

Adipose tissue and atherosclerosis: exploring the connection

The prevalence of obesity, especially among the young, is dramatically increasing in the United States. Obesity is associated with accelerated atherosclerosis and increased rates of cardiovascular death. There are many plausible mechanisms by which an increase in adipose tissue could adversely affect the vessel wall. These include the changes in blood pressure, glucose level, lipid/lipoprotein metabolism, and systemic inflammation. In addition, factors secreted by adipose tissue may directly influence vessel wall homeostasis by influencing the function of endothelial cells, arterial smooth muscle cells, and macrophages in the vessel wall. There is general agreement that central, as opposed to peripheral, adipose tissue confers the most cardio-metabolic risk. Although the basis of this differential risk has not been not established, the pattern of gene expression and secretory products in visceral fat would be predicted to be more atherogenic compared with that in subcutaneous peripheral fat. Numerous studies have shown the beneficial effects of weight loss on markers of cardiovascular risk but fewer have demonstrated improvement in direct measures of large vessel disease. The unfolding role of adipose tissue as an important metabolic and secretory organ provides new opportunities for developing more effective approaches for preventing obesity and its atherosclerotic complications.     

Gender difference in postprandial lipemia : importance of visceral adipose tissue accumulation.

Insulin resistance, hyperinsulinemia, hypertriglyceridemia, and low HDL-cholesterol concentrations are common features of a plurimetabolic syndrome, which increases the risk of coronary artery disease. Although it has been proposed that the development of atherosclerosis through alterations in plasma lipid levels could be a postprandial phenomenon, most studies on gender differences in plasma lipoprotein-lipid concentrations have reported fasting levels. Therefore, the aim of our study was to examine the response of postprandial triglyceride-rich lipoproteins to a standardized meal in 63 men and 25 women. In addition to the measurement of fasting and postprandial plasma lipid levels, numerous physical and metabolic variables were assessed, including body composition by underwater weighing and body fat distribution by computed tomography. Although no gender difference was noted in total body fat mass, men were characterized by a preferential accumulation of abdominal adipose tissue as revealed by an increased waist circumference and a greater visceral adipose tissue accumulation (50% difference) compared with women (P<0.001). Men also showed a greater plasma triglyceride response (P<0.005) as well as increased postprandial insulin and free fatty acid levels compared with women (P<0.01). Visceral adipose tissue was significantly associated with the postprandial triglyceride response in both genders (men: r=0.49, P<0. 0001; women: r=0.43, P<0.05). Finally, when men and women were matched for visceral adipose tissue accumulation, the gender difference in postprandial plasma triglyceride response was eliminated. Thus results of the present study suggest that the well known gender difference in visceral adipose tissue accumulation is an important contributing factor involved in the exaggerated postprandial triglyceride-rich lipoprotein response noted in men compared with women.     

Role of the RIP140 corepressor in ovulation and adipose biology

RIP140 is a ligand-dependent corepressor for most, if not all, nuclear receptors. It is expressed widely in many different tissues, but the phenotype of mice devoid of RIP140 indicates that it plays a crucial role in the ovary and in adipose biology. Ovarian expression of RIP140 is cell-type-specific during follicular development and it is essential for oocyte release during ovulation, but not for luteinization of mature ovarian follicles. In adipose tissue, RIP140 is essential for normal fat accumulation and RIP140-null mice show decreased lipid storage even on a high-fat diet, with upregulation of mitochondrial uncoupling protein (UCP1) in some fat depots. Thus RIP140 plays a crucial role in female fertility and in energy homeostasis, and could be a target for infertility treatment, new contraceptive strategies or prevention of obesity.     

21st Century Advances in Multimodality Imaging of Obesity for Care of the Cardiovascular Patient

Although obesity is typically defined by body mass index criteria, this does not differentiate true body fatness, as this includes both body fat and muscle. Therefore, other fat depots may better define cardiometabolic and cardiovascular disease (CVD) risk imposed by obesity. Data from translational, epidemiological, and clinical studies over the past 3 decades have clearly demonstrated that accumulation of adiposity in the abdominal viscera and within tissue depots lacking physiological adipose tissue storage capacity (termed "ectopic fat") is strongly associated with the development of a clinical syndrome characterized by atherogenic dyslipidemia, hyperinsulinemia/glucose intolerance/type 2 diabetes mellitus, hypertension, atherosclerosis, and abnormal cardiac remodeling and heart failure. This state-of-the-art paper discusses the impact of various body fat depots on cardiometabolic parameters and CVD risk. Specifically, it reviews novel and emerging imaging techniques to evaluate adiposity and the risk of cardiometabolic diseases and CVD.     

Metabolic liver disease of obesity and role of adipose tissue in the pathogenesis of nonalcoholic fatty liver disease

Nonalcoholic fatty liver disease （NAFLD） is an increasingly recognized cause of liver-related morbidity and mortality. It can develop secondary to numerous causes but a great majority of NAFLD cases occur in patients who are obese or present with other components of metabolic syndrome （hypertension, dyslipidemia, diabetes）. This is called primary NAFLD and insulin resistance plays a key role in its pathogenesis. Obesity is characterized by expanded adipose tissue, which is under a state of chronic inflammation. This disturbs the normal storage and endocrine functions of adipose tissue. In obesity, the secretome （adipokines, oytokines, free fatty acids and other lipid moieties） of fatty tissue is amplified, which through its autocrine, paracrine actions in fat tissue and systemic effects especially in the liver leads to an altered metabolic state with insulin resistance （IR）. IR leads to hyperglycemia and reactive hyperinsulinemia, which stimulates lipid-accumulating processes and impairs hepatic lipid metabolism. IR enhances free fatty acid delivery to liver from the adipose tissue storage due to uninhibited lipolysis. These changes result in hepatic abnormal fat accumulation, which may initiate the hepatic IR and further aggravate the altered metabolic state of whole body. Hepatic steatosis can also be explained by the fact that there is enhanced dietary fat delivery and physical inactivity. IR and NAFLD are also seen in various lipodystrophic states in contrary to popular belief that these problems only occur due to excessive adiposity in obesity. Hence, altered physiology of adipose tissue is central to development of IR, metabolic syndrome and NAFLD.