肥胖可能与病毒感染有关

随着生活水平的提高,肥胖已呈现为全球性问题.当今已将肥胖与艾滋病、癌症并称为21世纪威胁人类健康的三大疾病.而其中肥胖症则是人类健康的最大威胁.当前人们普遍认为肥胖是由于遗传、过食、运动不足、代谢异常、内分泌异常、脑疾患等因素引起.但是这些均不能完满地解释肥胖的成因.为此,美国科学家Dhurandhar等提出了一种新的解释.他们认为,肥胖可能与病毒感染有关[1].并已研究发现了第1株可引起动物肥胖的人腺病毒血清36型(adenouirus Ad-36),这是迄今所发现的第1株与肥胖有关的人腺病毒[2].证据表明,该病毒感染在动物肥胖发病中起着重要作用[2~5].是否能导致人类肥胖尚不得而知.但是,有关肥胖的病毒发现使肥胖成因的研究有了新的思考,为人类进一步了解肥胖问题的根源,以及肥胖的防治开辟了新的领域,展现出新的希望.至于病毒导致动物肥胖的具体机理以及人类肥胖是否与病毒感染有关至今尚不明确,有待深入研究.     

肥胖可能与病毒感染有关

随着生活水平的提高,肥胖已呈现为全球性问题。当今已将肥胖与艾滋病、癌症并称为21世纪威胁人类健康的三大疾病。而其中肥胖症则是人类健康的最大威胁。当前人们普遍认为肥胖是由于遗传、过食、运动不足、代谢异常、内分泌异常、脑疾患等因素引起。但是这些均不能完满地解释肥胖的成因。为此,美国科学家Dhurandhar等提出了一种新的解释。他们认为,肥胖可能与病毒感染有关。     

肥胖孕妇肠道菌群与子代肥胖的相关性

妊娠期肥胖发生率在世界范围内呈上升趋势,成为影响人类健康的公共卫生问题。肥胖母亲肠道菌群失调导致婴儿早期定植菌群异常,而婴儿早期菌群定植情况与其日后生长发育密切相关,容易导致成年后出现肥胖、胰岛素抵抗、代谢综合征等疾病。因此针对肥胖孕妇肠道菌群分析,以及婴儿肠道菌群及生长发育的分析,对于孕妇孕期管理、健康宣教提高国民整体身体素质具有重要意义。     

森林砍伐对苦槠种群遗传结构的影响

人类活动严重干扰着自然生态系统,其中砍伐是对森林生态系统最常见的干扰之一,它导致森林退化,植物种群变小,甚至灭绝,遗传多样性也随之下降。当被破坏的森林未被转换性利用时,则会逐渐恢复,但由于瓶颈效应,恢复起来的生态系统中植物种群的遗传结构可能会改变。恢复种群遗传组成的改变一方面与干扰的强度、频度和持续时间有关,另一方面,也受植物生活史特点的深刻影响。然而,我国对于砍伐后恢复起来的森林生态系统中生物多样性的改变,尤其是遗传多样性的改变的研究并不多见。研究在浙江省宁波市天童国家森林公园及周边地区选择了5个苦槠种群,采用SSR微卫星标记来分析砍伐对苦槠种群遗传结构的影响。5对多态SSR引物共得到了29个等位基因。种群内维持了较高的遗传多样性,种群间遗传分化程度较低,基因流达8．68。恢复林和成熟林种群的遗传多样性相差不大,以阿育王寺地区恢复种群的最高;表明砍伐对于苦槠种群遗传多样性的影响不大,这与苦槠较强的萌条能力有关。尽管如此,在恢复种群中观察到近期的种群瓶颈,显示出砍伐对种群遗传组成的影响;而在一个成熟林中也观察到种群瓶颈,这是因片断化导致种群变小之故。植被保存最好的天童国家森林公园内苦槠种群的遗传多样性却较低,这可能与成熟林中苦槠优势度较低有关。     

单基因肥胖的致病基因概述

肥胖是人类体质研究中的重要组成部分,发生率在世界范围内呈快速上升趋势,其预防与控制是当今研究的重要课题。肥胖受遗传与环境因素的共同作用,其中遗传因素对其发生至关重要。截至目前,已有14种单基因肥胖的致病基因被确认,涉及了食欲调控和食物摄取、能量消耗和脂肪细胞分化调控等方面。本文概述了上述基因在单基因肥胖研究中的情况,旨在加深对肥胖病理生理学机制的理解,并为其相关研究的开展提供参考。     

具有脂肪代谢功能的果蝇细胞

果蝇与人类有很多共同基因,实践证明它们对了解几种人类疾病来说很有用,但它们的脂肪代谢机制一直是个谜,这限制了果蝇（及其很多遗传工具）在肝病和肥胖研究中的应用。所以关于果蝇体内也存在具有脂肪代谢功能的细胞、与人类肝脏中同样功能的细胞类似的发现,可以说是一项重要进展。这些细胞是绛细胞（oenocyte）,首次于140多年前发现于昆虫,但以前未发现其有某种特定功能。     

多基因肥胖风险预测及其对生活方式影响的研究进展

肥胖是人类体质研究中的重要组成部分,受遗传与生活方式的共同作用,其发生率在世界范围内呈快速上升趋势,其预防与控制是重要的研究课题。根据致病的基因数不同,肥胖可分为单基因肥胖综合征、单基因肥胖和多基因肥胖。本文对迄今为止的多基因肥胖风险的预测及其对生活方式影响研究中的主要结果进行综述,旨在为相关研究的开展提供参考。     

儿童肥胖的生化机制和遗传特征

肥胖是遗传因素和环境因素共同作用的结果.儿童肥胖的易感性主要由遗传因素决定,具有较高的遗传率和遗传特征.瘦蛋白-促黑素细胞激素调控途径中断、单基因突变以及染色体重排都可能引起肥胖.对儿童肥胖的遗传学研究为治疗靶向药物的研制提供依据.     

慢性代谢性疾病的环境与遗传交互作用以及早期预防

随着我国经济的发展和营养与生活方式的迅速变迁,近年来我国居民肥胖、2型糖尿病等慢性代谢性疾病患病率激增,已成为影响国民健康最主要的威胁。有研究显示:与白种人相比,亚洲人具有较高的2型糖尿病遗传易感性,这可能与"代谢性肥胖"表型和遭遇营养转型中的"致肥胖环境"有关。大量的研究结果表明,此类慢性代谢性疾病是遗传和环境因素交互作用的结果。随着全基因组关联研究开展,目前已发现了20多个肥胖和2型糖尿病易感基因,不仅揭示了不同种族人群在基因结构和效应值方面存在着差异,但同时也发现遗传方面的差异仍无法完全解释东西方人在发病风险方面的不同。膳食、生活方式等环境因素仍被认为是2型糖尿病发病中的重要决定因素。在全基因组关联研究后时代,国际上的研究将更加强调基因—基因、基因—环境、基因—表型之间的交互作用对代谢性疾病的影响和相关的机制。事实上,有研究表明,各种基因多态性、炎性因子和脂肪细胞因子等都可能成为早期诊断的生物标记物,而通过改变膳食和生活方式则是目前国际公认的预防和控制慢性代谢性疾病最有效的方法。然而,我国尤为缺乏在大规模前瞻性流行病学研究中对导致慢性代谢性疾病流行的主要遗传和环境因素,以及基因—环境相互作用对健康的影响方面的系统的研究。而这类研究将为建立适用于中国人群遗传和表型特征的早期诊断生物标记物和有效预防干预策略奠定基础。     

人类线粒体DNA的分子遗传特性

人类线粒体DNA(mitochodrialDNA,mtDNA)是存在于细胞核外唯一的遗传物质,具有独特的分子遗传特性,mtDNA突变可导致人类各种退行性疾病和与衰老相关的疾病发生。     

Genetics of obesity

Considerable attention is currently being paid to the secular changes in food intake and physical activity that underlie the increase in the prevalence of obesity that is apparent in many societies. While this is laudable it would be unwise to view these environmental factors in isolation from the biological factors that normally control body weight and composition and the compelling evidence that inter-individual differences in susceptibility to obesity have strong genetic determinants. This is particularly important, as it is only in the past decade that we have begun to obtain substantive information regarding the molecular constituents of pathways controlling mammalian energy balance and therefore, for the first time, are in a position to achieve a better mechanistic understanding of this disease. Population-based association and linkage studies have highlighted a number of loci at which genetic variation is associated with obesity and related phenotypes and the identification and characterization of monogenic obesity syndromes has been particularly fruitful. While there is widespread acceptance that hereditary factors might predispose to human obesity, it is frequently assumed that such factors would influence metabolic rate or the selective partitioning of excess calories into fat. However, it is notable that, thus far, all monogenic defects causing human obesity actually disrupt hypothalamic pathways and have a profound effect on satiety and food intake. To conclude, the evidence we have to date suggests that the major impact of genes on human obesity is just as likely (or perhaps more likely) to directly impact on hunger, satiety and food intake rather than metabolic rate or nutrient partitioning. At the risk of oversimplification, it seems that from an aetiological/genetic standpoint, human obesity appears less a metabolic than a neuro-behavioural disease.     

Comparative Analyses of QTLs Influencing Obesity and Metabolic Phenotypes in Pigs and Humans

The pig is a well-known animal model used to investigate genetic and mechanistic aspects of human disease biology. They are particularly useful in the context of obesity and metabolic diseases because other widely used models (e.g. mice) do not completely recapitulate key pathophysiological features associated with these diseases in humans. Therefore, we established a F2 pig resource population (n = 564) designed to elucidate the genetics underlying obesity and metabolic phenotypes. Segregation of obesity traits was ensured by using breeds highly divergent with respect to obesity traits in the parental generation. Several obesity and metabolic phenotypes were recorded (n = 35) from birth to slaughter (242 ± 48 days), including body composition determined at about two months of age (63 ± 10 days) via dual-energy x-ray absorptiometry (DXA) scanning. All pigs were genotyped using Illumina Porcine 60k SNP Beadchip and a combined linkage disequilibrium-linkage analysis was used to identify genome-wide significant associations for collected phenotypes. We identified 229 QTLs which associated with adiposity- and metabolic phenotypes at genome-wide significant levels. Subsequently comparative analyses were performed to identify the extent of overlap between previously identified QTLs in both humans and pigs. The combined analysis of a large number of obesity phenotypes has provided insight in the genetic architecture of the molecular mechanisms underlying these traits indicating that QTLs underlying similar phenotypes are clustered in the genome. Our analyses have further confirmed that genetic heterogeneity is an inherent characteristic of obesity traits most likely caused by segregation or fixation of different variants of the individual components belonging to cellular pathways in different populations. Several important genes previously associated to obesity in human studies, along with novel genes were identified. Altogether, this study provides novel insight that may further the current understanding of the molecular mechanisms underlying human obesity.     

Past, present and future strategies to study the genetics of body weight regulation.

Genetic advances have made remarkable progress towards our understanding of body weight regulation. Much of our current knowledge has come from the cloning and characterisation of the genes responsible for obesity syndromes in the mouse, and the identification of homologous mutations causing rare forms of obesity in humans. Gene targeting experiments in mice have been instrumental in confirming the importance of many genes in the aetiology of obesity, and the existence of a fundamental physiological pathway that controls energy balance is becoming clear. The genetic determinants that underlie common forms of human obesity are largely polygenic, with most genes producing small effects. Thus, elucidating the many genetic determinants of obesity is a current challenge for modern geneticists. Despite the inherent difficulties, progress has been made through linkage/association studies and a genetic map of quantitative trait loci for human obesity is beginning to emerge. Obesity research is now very much in a transition period. Not so long ago, access to high throughput screening, as well as microarray and proteomic techniques, was prohibitively expensive and available only to the few. In recent years, these technologies have become more accessible to the larger scientific community and, in this paper, we will discuss how such technological advances are likely to drive the next wave of progress in obesity research. For example, large-scale mutagenesis screens in rodents coupled with high throughput screening are likely to emerge as important technologies for identifying genes previously unexpected to be involved in body weight regulation. Furthermore, applications of microarray and proteomic techniques will further refine our understanding of currently known peptides as well as identify novel pathways and molecules which are involved in energy homeostasis.     

Diet-induced obesity in zebrafish shares common pathophysiological pathways with mammalian obesity

Background  

Obesity is a multifactorial disorder influenced by genetic and environmental factors. Animal models of obesity are required to help us understand the signaling pathways underlying this condition. Zebrafish possess many structural and functional similarities with humans and have been used to model various human diseases, including a genetic model of obesity. The purpose of this study was to establish a zebrafish model of diet-induced obesity (DIO).     

Primary cilia in energy balance signaling and metabolic disorder

Energy homeostasis in our body system is maintained by balancing the intake and expenditure of energy. Excessive accumulation of fat by disrupting the balance system causes overweight and obesity, which are increasingly becoming global health concerns. Understanding the pathogenesis of obesity focused on studying the genes related to familial types of obesity. Recently, a rare human genetic disorder, ciliopathy, links the role for genes regulating structure and function of a cellular organelle, the primary cilium, to metabolic disorder, obesity and type II diabetes. Primary cilia are microtubule based hair-like membranous structures, lacking motility and functions such as sensing the environmental cues, and transducing extracellular signals within the cells. Interestingly, the subclass of ciliopathies, such as Bardet-Biedle and Alström syndrome, manifest obesity and type II diabetes in human and mouse model systems. Moreover, studies on genetic mouse model system indicate that more ciliary genes affect energy homeostasis through multiple regulatory steps such as central and peripheral actions of leptin and insulin. In this review, we discuss the latest findings in primary cilia and metabolic disorders, and propose the possible interaction between primary cilia and the leptin and insulin signal pathways which might enhance our understanding of the unambiguous link of a cell’s antenna to obesity and type II diabetes. [BMB Reports 2015; 48(12): 647-654]     

Molecular genetics of human obesity: A comprehensive review

Obesity and its related health complications is a major problem worldwide. Hypothalamus and their signalling molecules play a critical role in the intervening and coordination with energy balance and homeostasis. Genetic factors play a crucial role in determining an individual's predisposition to the weight gain and being obese. In the past few years, several genetic variants were identified as monogenic forms of human obesity having success over common polygenic forms. In the context of molecular genetics, genome-wide association studies (GWAS) approach and their findings signified a number of genetic variants predisposing to obesity. However, the last couple of years, it has also been noticed that alterations in the environmental and epigenetic factors are one of the key causes of obesity. Hence, this review might be helpful in the current scenario of molecular genetics of human obesity, obesity-related health complications (ORHC), and energy homeostasis. Future work based on the clinical discoveries may play a role in the molecular dissection of genetic approaches to find more obesity-susceptible gene loci.     

Greater replication and differentiation of preadipocytes in inherited corticosteroid-binding globulin deficiency

Glucocorticoids are pivotal for adipose tissue development. Rodent studies suggest that corticosteroid-binding globulin (CBG) modulates glucocorticoid action in adipose tissue. In humans, both genetic CBG deficiency and suppressed CBG concentrations in hyperinsulinemic states are associated with obesity. We hypothesized that CBG deficiency in humans modulates the response of human preadipocytes to glucocorticoids, predisposing them to obesity. We compared normal preadipocytes with subcultured preadipocytes from an individual with the first ever described complete deficiency of CBG due to a homozygous null mutation. CBG-negative preadipocytes proliferated more rapidly and showed greater peroxisome proliferator-activated receptor-gamma-mediated differentiation than normal preadipocytes. CBG was not expressed in normal human preadipocytes. Glucocorticoid receptor number and binding characteristics and 11beta-hydroxysteroid dehydrogenase activity were similar for CBG-negative and normal preadipocytes. We propose that the increased proliferation and enhanced differentiation of CBG-negative preadipocytes may promote adipose tissue deposition and explain the obesity seen in individuals with genetic CBG deficiency. Furthermore, these observations may be relevant to obesity occurring with suppressed CBG concentrations associated with hyperinsulinemia.     

OB gene not linked to human obesity in Mexican American affected sib pairs from Starr County,Texas

Obesity is a highly prevalent disease, which is associated with a number of chronic conditions and, as such, represents a major public health burden. Numerous studies indicate that there is a genetic component contributing to interindividual variability in obesity. The discovery of the ob gene in mice, mutations in which produce extreme obesity and non-insulin-dependent diabetes mellitus (NIDDM), provides a prime candidate gene for human obesity. We investigated linkage between the human OB gene and obesity in a sample of Mexican Americans from Starr County, Texas. Markers D7S635 and D7S1875, estimated to lie within a region approximately 290 to 400 kb proximal to the OB gene, were used to genotype 177 obese individuals distributed in 64 sibships. Obesity was defined as a body mass index (BMI) above 30 kg/m². Linkage analyses for affected sibling pairs provided no evidence for linkage in this sample. In addition, differences between siblings for weight, BMI, systolic and diastolic blood pressure, percent body fat, waist-to-hip ratio, and blood lipid measures were not significantly related to number of alleles shared identical by state (IBS) for either of the two markers. While the OB gene may be involved in the metabolic sequences leading to obesity, the present linkage results do not support the existence of common genetic variation at or near the OB locus that increases risk for human obesity. Received: 17 April 1996 / Revised: 18 June 1996     

Genetic variation and correlation of dietary response in an advanced intercross mouse line produced from two divergent growth lines

Levels of human obesity have increased over the past 20 years worldwide, primarily due to changes in diet and activity levels. Although environmental changes are clearly responsible for the increasing prevalence of obesity, individuals may show genetic variation in their response to an obesogenic environment. Here, we measure genetic variation in response to a high-fat diet in a mouse model, an F16 Advanced Intercross Line derived from the cross of SM/J and LG/J inbred mouse strains. The experimental population was separated by sex and fed either a high-fat (42% of energy from fat) or low-fat (15% of energy from fat) diet. A number of phenotypic traits related to obesity and diabetes such as growth rate, glucose tolerance traits, organ weights and fat pad weights were collected and analysed in addition to serum levels of insulin, free fatty acids, cholesterol and triglycerides. Most traits are different between the sexes and between dietary treatments and for a few traits, including adult growth, fat pad weights, insulin and glucose tolerance, the dietary effect is stronger in one sex than the other. We find that fat pad weights, liver weight, serum insulin levels and adult growth rates are all phenotypically and genetically correlated with one another in both dietary treatments. Critically, these traits have relatively low genetic correlations across environments (average r =0.38). Dietary responses are also genetically correlated across these traits. We found substantial genetic variation in dietary response and low cross environment genetic correlations for traits aligned with adiposity. Therefore, genetic effects for these traits are different depending on the environment an animal is exposed to.     

Quantitative and molecular genetic determination of protein and fat deposition

After 30 years of selection, breeding of the pig breed sus scrofa Piétrain has resulted in reduced backfat thickness (from 3.2 to 1.9 mm) and increased loin muscle area (40 to 60 cm2) which indicates high genetic determination of these body composition traits. The use of sophisticated quantitative genetic methods that include all genetic relationships of large populations has led to a high response to selection of these traits. Selection on feed intake, lean and fat tissue growth using nonlinear functions to optimise these traits during the entire growth period in a biological model offers the opportunity to further improve total genetic potential. Protein and lipid deposition rates during the entire growth period have to be known for this biological model to be applied; thus knowledge of the genetic background of these traits is of high economic value. With the use of molecular genetic methods, such as candidate gene and genome scan approaches, the identification of genes for obesity and growth can be obtained. In sus scrofa, candidate genes associated with obesity and growth include Leptin Receptor, Melanocortin-4 Receptor, Agouti related protein, Heart fatty acid binding protein 3, and Insulin-like growth factor 2. Some of these candidate genes also explain variation in obesity levels in humans. Initial genome-wide scans have identified quantitative trait loci (QTL) on chromosomes 1, 4, 5, 7 and X for obesity and on chromosomes 1, 4, 7, 8, 13 and 18 for growth. Physiological candidate genes and predispositional QTL for obesity are not always located on the same chromosome; this is known the "polygenic paradox". Use of a nonlinear growth function is recommended in order to give more insight into the physiological regulation of obesity traits. Sus scrofa is an excellent model organism to examine the genetic regulation of obesity. The conservation of DNA sequence and chromosomal segments between sus scrofa and homo sapiens will permit easy transfer of results to human studies.