成脂调控网络(ARN)数据库的分析和预测功能

脂肪组织中脂类的过量积累会导致肥胖,进而引发心血管疾病、二型糖尿病和其他疾病.成脂是指干细胞分化为能够积聚脂滴的脂肪细胞的过程,受到一个复杂且高度协调的基因表达网络的调节,为促进成脂调控中关键基因和通路的发现,探索脂肪生成的分子调控机理,在之前的研究中,本实验室通过对成脂相关文献进行文本挖掘构建出一个包含3万多条成脂相关数据和信息的成脂调控网络(Adipogenesis Regulation Network,ARN)数据库(http://210.27.80.93/arn/).为了进一步充分发掘ARN数据库促进成脂相关研究的潜在价值,本研究通过“开放的”和“闭合的”两种构建假说的原理,设计出能够用于分析成脂分化相关试验数据或构建科学假说的在线分析工具-ARN-analysis.另外,通过对成脂调控网络中各节点(基因和小分子RNA)的互作关系数、差异表达记录数和互作关系预测数进行统计分析,计算得到体现各节点重要性的节点影响值(impact factor,IF).最后,通过对成脂调控网络中各节点的互作关系进行统计分析和作图,探索了成脂调控网络的拓扑结构.结果显示,ARN数据库的分析工具能够有效分析“节点相关”、“表达相关”及“用户录入”3类数据,帮助科研人员分析试验数据或构建科学假说.节点的IF值能够帮助科研人员快速识别重要的节点或假说,对调控网络拓扑结构的分析能加深对成脂调控机理的认识.本研究对成脂专业数据库的分析和预测功能的探索,为专业研究人员分析数据和构建假说提供了新的途径,探索了运用过去积累的大量科研数据促进未来的科研实践的可能性.     

Characterization of the gut microbiota in leptin deficient obese mice – Correlation to inflammatory and diabetic parameters

Gut microbiota have been implicated as a relevant factor in the development of type 2 diabetes mellitus (T2DM), and its diversity might be a cause of variation in animal models of T2DM. In this study, we aimed to characterise the gut microbiota of a T2DM mouse model with a long term vision of being able to target the gut microbiota to reduce the number of animals used in experiments. Male B6.V-Lep^ob/J mice were characterized according to a number of characteristics related to T2DM, inflammation and gut microbiota. All findings were thereafter correlated to one another in a linear regression model. The total gut microbiota profile correlated to glycated haemoglobin, and high proportions of Prevotellaceae and Lachnospiraceae correlated to impaired or improved glucose intolerance, respectively. In addition, Akkermansia muciniphila disappeared with age as glucose intolerance worsened. A high proportion of regulatory T cells correlated to the gut microbiota and improved glucose tolerance. Furthermore, high levels of IL-10, IL-12 and TNF-α correlated to impaired glucose tolerance, blood glucose or glycated haemoglobin. The findings indicate that gut microbiota may contribute to variation in various disease read-outs in the B6.V-Lep^ob/J model and considering them in both quality assurance and data evaluation for the B6.V-Lep^ob/J model may have a reducing impact on the inter-individual variation.     

Effects of Body Condition Score on the Reproductive Physiology of the Broodmare: A Review

The feeding management of broodmares is essential for breeding and successfully raising a healthy foal. A feeding regime will depend on the breed of mare, her age, body condition score (BCS), and general health and management. To maintain the broodmare in adequate body condition, her BCS should be ascertained and a feed regime implemented to maintain her optimum BCS and body weight, thus increasing fertility, milk yield, and the health of the mare and foal. Excesses and deficits in nutrition of the broodmare are regularly observed because nutritional recommendations are not well known or often not well instigated by horse breeders. Some short-term unbalanced rations are of little detriment to the health of the broodmare, but prolonged unbalanced rations can predispose the broodmare and foal to nutritional- and pathologic-related problems. By providing the broodmare with sufficient dietary energy, key nutrients, protein, and minerals in a balanced form, the risk of the foal developing orthopedic diseases will be greatly diminished. Obesity in the broodmare causes increased fetal adiposity, which can affect growth and performance of the adult horse. Conversely, undernutrition of the broodmare can cause intrauterine growth retardation of the fetus, resulting in altered development of the system(s) involved, which may have long-term effects on the horse that manifest during fetal, neonatal, or even adult life.     

Use of starting condition score to estimate changes in body weight and composition during weight loss in obese dogs

Prior to starting a weight loss programme, target weight (TW) is often estimated, using starting body condition score (BCS). The current study assessed how well such estimates perform in clinical practice. Information on body weight, BCS and body composition was assessed before and after weight loss in 28 obese, client-owned dogs. Median decrease in starting weight per BCS unit was 10% (5–15%), with no significant difference between dogs losing moderate (1–2 BCS points) or marked (3–4 BCS points) amounts of weight (P = 0.627). Mean decrease in body fat per BCS unit change was 5% (3–9%). A model based on a change of 10% of starting weight per unit of BCS above ideal (5/9) most closely estimated actual TW, but marked variability was seen. Therefore, although such calculations may provide a guide to final TW in obese dogs, they can either over- or under-estimate the appropriate end point of weight loss.     

FBW7 inhibits ox-LDL-induced granulosa cell apoptosis by promoting NOX1 degradation

AIM To investigate the effect of F-box and WD repeat domain containing protein 7 （FBW7） on the injury of granulosa cells （GCs） induced by oxidized low-density lipopretion （ox-LDL） stimulation and its potential mechanism. METHODS The GCs isolated from women of reproductive age with different obesity levels, the GCs isolated from high fatty diet （HFD）-fed rats, and the ox-LDL-treated rat GCs were collected, and the expression of FBW7 was detected by Western blot. After the rat GCs were infected with adenovirus encoding FBW7 （Ad-FBW7）, the cells were treated with ox-LDL （80 mg/L） for 48 h, and then the cell viability, apoptosis, NADPH oxidase （NOX） activity and the key subunit proteins of NOX were detected by CCK-8 assay, Annexin V/PI staining, lucigenin chemiluminescence and Western blot, respectively. The effect of FBW7 over-expression on NOX1 degradation was evaluated by cycloheximide （CHX） chase assay. RESULTS The expression of FBW7 was lower in the GCs isolated from obese women of reproductive age, the GCs isolated from HFD-fed rats, and the ox-LDL-treated rat GCs （P<0.05）. Over-expression of FBW7 inhibited ox-LDL-induced injury of GCs, NOX activity, and NOX1 expression （P<0.05）. The results of CHX chase assay showed that over-expression of FBW7 accelerated the degradation of NOX1 protein under ox-LDL condition （P<0.05）. CONCLUSION Over-expression of FBW7 reduces ox-LDL-induced injury of GCs by accelerating NOX1 degradation and then weakening NOX activity.     

Gut microbiota—a positive contributor in the process of intermittent fasting-mediated obesity control

Historically, intermittent fasting (IF) has been considered as an effective strategy for controlling the weight of athletes before competition. Along with excellent insight into its application in various spaces by numerous studies, increasing IF-mediated positive effects have been reported, including anti-aging, neuroprotection, especially obesity control. Recently, the gut microbiota has been considered as an essential manipulator for host energy metabolism and its structure has been reported to be sensitive to dietary structure and habits, indicating that there is a potential and strong association between IF and gut microbiota. In this paper, we focus on the crosstalk between these symbionts and energy metabolism during IF which hold the promise to optimize host energy metabolism at various physical positions, including adipose tissue, liver and intestines, and further improve milieu internal homeostasis. Moreover, this paper also discusses the positive function of a potential recommendatory strain (Akkermansia muciniphila) based on the observational data for IF-mediated alternated pattern of gut microbiota and a hopefully regulatory pathway (circadian rhythm) for gut microbiota in IF-involved improvement on host energy metabolism. Finally, this review addresses the limitation and perspective originating from these studies, such as the association with tissue-specific bio-clock and single strain research, which may continuously reveal novel viewpoints and mechanisms to understand the energy metabolism and develop new strategies for treating obesity, diabetes, and metabolic disorders.     

Maternal obesity in ewes results in reduced fetal pancreatic β-cell numbers in late gestation and decreased circulating insulin concentration at term

About 30% of U.S. women of reproductive age are obese, a condition linked to offspring obesity and diabetes. This study utilized an ovine model of maternal obesity in which ewes are overfed to induce obesity at conception and throughout gestation. At mid-gestation, fetuses from these obese ewes are macrosomic, hyperglycemic, and hyperinsulinemic, and they exhibited markedly increased pancreatic weight and β-cell numbers compared with fetuses of ewes fed to requirements. This study was conducted to establish fetal pancreatic phenotype and function in late gestation and at term in this ovine model. Multiparous ewes were fed a control (C, 100% National Research Council [NRC] recommendations) or obesogenic (OB, 150% NRC) diet from 60 days before conception to necropsy at day 135 of gestation or to lambing. No differences were observed in fetal size or weight on day 135 or in lamb birth weights between C and OB ewes. In contrast to our previously published results at mid-gestation, pancreatic weights (P < 0.01) and β-cell numbers (P < 0.05) of OB fetuses were markedly lower than those from C fetuses, whereas the β-cell apoptotic rate was increased (P < 0.05) in day 135 OB versus C fetuses. At birth, blood insulin concentration was lower (P < 0.05) and glucose level was higher (P < 0.05) in newborn lambs from OB versus C ewes. These data demonstrate differential impacts of maternal obesity on fetal pancreatic growth and β-cell numbers during early and late gestation. During the first half of gestation there was a marked increase in pancreatic growth, β-cell proliferation, and insulin secretion, followed by a reduction in pancreatic growth and β-cell numbers in late gestation, resulting in reduced circulating insulin at term. It is speculated that the failure of the pancreas to return to a normal cellular composition and function postnatally could result in glucose/insulin dysregulation, leading to obesity, glucose intolerance, and diabetes in postnatal life.