Liraglutide Improves Hypertension and Metabolic Perturbation in a Rat Model of Polycystic Ovarian Syndrome

Polycystic ovarian syndrome (PCOS) is the most common endocrine disorder in women of reproductive age, with a prevalence of 5–8%. Type 2 diabetes and cardiovascular disease (CVD) are its long-term complications. Targeted therapies addressing both these complications together are lacking. Glucagon like peptide-1 (GLP-1) agonists that are used to treat type 2 diabetes mellitus have beneficial effects on the cardiovascular system. Hence we hypothesized that a GLP-1 agonist would improve both cardiovascular and metabolic outcomes in PCOS. To test this hypothesis, we used an established rat model of PCOS. Prepubertal female Sprague Dawley rats were sham-implanted or implanted s.c. with dihydrotestosterone (DHT) pellets (90 day release; 83μg/day). At 12 wks of age, sham implanted rats received saline injections and the DHT treated animals were administered either saline or liraglutide (0.2mg/kg s.c twice daily) for 4 weeks. Subgroups of rats were implanted with telemeters between 12-13 weeks of age to monitor blood pressure. DHT implanted rats had irregular estrus cycles and were significantly heavier than the control females at 12 weeks (mean± SEM 251.9±3.4 vs 216.8±3.4 respectively; p<0.05) and 4 weeks of treatment with liraglutide in DHT treated rats significantly decreased body weight (mean± SEM 294.75 ±3.2 in DHT+ saline vs 276.25±2.7 in DHT+ liraglutide group respectively; p<0.01). Liraglutide treatment in the DHT implanted rats significantly improved glucose excursion during oral glucose tolerance test (area under the curve: DHT+ saline 28674±310 vs 24990± 420 in DHT +liraglutide p <0.01). DHT rats were hypertensive and liraglutide treatment significantly improved mean arterial pressure. These results suggest that GLP-1 treatment could improve DHT–induced metabolic and blood pressure deficits associated with PCOS.     

Sensory Dysfunction of Bladder Mucosa and Bladder Oversensitivity in a Rat Model of Metabolic Syndrome

Purpose

To study the role of sensory dysfunction of bladder mucosa in bladder oversensitivity of rats with metabolic syndrome.

Materials and Methods

Female Wistar rats were fed a fructose-rich diet (60%) or a normal diet for 3 months. Based on cystometry, the fructose-fed rats (FFRs) were divided into a group with normal detrusor function or detrusor overactivity (DO). Acidic adenosine triphosphate (ATP) solution (5mM, pH 3.3) was used to elicit reflex micturition. Cystometric parameters were evaluated before and after drug administration. Functional proteins of the bladder mucosa were assessed by western blotting.

Results

Compared to the controls, intravesical acidic ATP solution instillation induced a significant increase in provoked phasic contractions in both FFR groups and a significant decrease in the mean functional bladder capacity of group DO. Pretreatment with capsaicin for C-fiber desentization, intravesical liposome for mucosal protection, or intravenous pyridoxal 5-phosphate 6-azophenyl-2′,4′-disulfonic acid for antagonized purinergic receptors can interfere with the urodynamic effects of intravesical ATP in FFRs and controls. Over-expression of TRPV1, P2X₃, and iNOS proteins, and down-regulation of eNOS proteins were observed in the bladder mucosa of both fructose-fed groups.

Conclusions

Alterations of sensory receptors and enzymes in the bladder mucosa, including over-expression of TRPV1, P2X₃, and iNOS proteins, can precipitate the emergence of bladder phasic contractions and oversensitivity through the activation of C-afferents during acidic ATP solution stimulation in FFRs. The down-regulation of eNOS protein in the bladder mucosa of FFRs may lead to a failure to suppress bladder oversensitivity and phasic contractions. Sensory dysfunction of bladder mucosa and DO causing by metabolic syndrome are easier to elicit bladder oversensitivity to certain urothelium stimuli.     

Rescue of Fructose-Induced Metabolic Syndrome by Antibiotics or Faecal Transplantation in a Rat Model of Obesity

A fructose-rich diet can induce metabolic syndrome, a combination of health disorders that increases the risk of diabetes and cardiovascular diseases. Diet is also known to alter the microbial composition of the gut, although it is not clear whether such alteration contributes to the development of metabolic syndrome. The aim of this work was to assess the possible link between the gut microbiota and the development of diet-induced metabolic syndrome in a rat model of obesity. Rats were fed either a standard or high-fructose diet. Groups of fructose-fed rats were treated with either antibiotics or faecal samples from control rats by oral gavage. Body composition, plasma metabolic parameters and markers of tissue oxidative stress were measured in all groups. A 16S DNA-sequencing approach was used to evaluate the bacterial composition of the gut of animals under different diets. The fructose-rich diet induced markers of metabolic syndrome, inflammation and oxidative stress, that were all significantly reduced when the animals were treated with antibiotic or faecal samples. The number of members of two bacterial genera, Coprococcus and Ruminococcus, was increased by the fructose-rich diet and reduced by both antibiotic and faecal treatments, pointing to a correlation between their abundance and the development of the metabolic syndrome. Our data indicate that in rats fed a fructose-rich diet the development of metabolic syndrome is directly correlated with variations of the gut content of specific bacterial taxa.     

Dysfunction of Inflammation-Resolving Pathways Is Associated with Exaggerated Postoperative Cognitive Decline in a Rat Model of the Metabolic Syndrome

The cholinergic antiinflammatory pathway (CAP), which terminates in the spleen, attenuates postoperative cognitive decline (PCD) in rodents. Surgical patients with metabolic syndrome exhibit exaggerated and persistent PCD that is reproduced in postoperative rats selectively bred for easy fatigability and that contain all features of metabolic syndrome (low-capacity runners [LCRs]). We compared the CAP and lipoxin A₄ (LXA₄), another inflammation-resolving pathway in LCR, with its counterpart high-capacity runner (HCR) rats. Isoflurane-anesthetized LCR and HCR rats either underwent aseptic trauma involving tibial fracture (surgery) or not (sham). At postoperative d 3 (POD3), compared with HCR, LCR rats exhibited significantly exaggerated PCD (trace fear conditioning freezing time 43% versus 57%). Separate cohorts were killed at POD3 to collect plasma for LXA4 and to isolate splenic mononuclear cells (MNCs) to analyze CAP signaling, regulatory T cells (Tregs) and M2 macrophages (M2 Mφ). Under lipopolysaccharide (LPS) stimulation, tumor necrosis factor (TNF)-α produced by splenic MNCs was 117% higher in LCR sham and 52% higher in LCR surgery compared with HCR sham and surgery rats; LPS-stimulated TNF-α production could not be inhibited by an α7 nicotinic acetylcholine receptor agonist, whereas inhibition by the β₂ adrenergic agonist, salmeterol, was significantly less (−35%) than that obtained in HCR rats. Compared to HCR, sham and surgery LCR rats had reduced β₂ adrenergic receptor–expressing T lymphocytes (59%, 44%), Tregs (47%, 54%) and M2 Mφ (45%, 39%); surgical LCR rats’ hippocampal M2 Mφ was 66% reduced, and plasma LXA4 was decreased by 120%. Rats with the metabolic syndrome have ineffective inflammation-resolving mechanisms that represent plausible reasons for the exaggerated and persistent PCD.     

Mecp2影响Rett综合征中代谢功能的研究进展

Rett综合征(RTT)是一种由X连锁的甲基CpG结合蛋白2(Mecp2)基因突变引起的神经系统疾病,突变致病的具体调节机制尚不清楚.对RTT的研究大多聚焦在中枢神经系统,越来越多的研究显示Mecp2在各种代谢系统中也发挥着重要作用.回顾了RTT发展历史、Mecp2的发现及主要作用,并综述了MeCP2在脂质代谢、线粒体...     

Searching for Genomic Region of High-Fat Diet-Induced Type 2 Diabetes in Mouse Chromosome 2 by Analysis of Congenic Strains

SMXA-5 mice are a high-fat diet-induced type 2 diabetes animal model established from non-diabetic SM/J and A/J mice. By using F2 intercross mice between SMXA-5 and SM/J mice under feeding with a high-fat diet, we previously mapped a major diabetogenic QTL (T2dm2sa) on chromosome 2. We then produced the congenic strain (SM.A-T2dm2sa (R0), 20.8–163.0 Mb) and demonstrated that the A/J allele of T2dm2sa impaired glucose tolerance and increased body weight and body mass index in the congenic strain compared to SM/J mice. We also showed that the combination of T2dm2sa and other diabetogenic loci was needed to develop the high-fat diet-induced type 2 diabetes. In this study, to narrow the potential genomic region containing the gene(s) responsible for T2dm2sa, we constructed R1 and R2 congenic strains. Both R1 (69.6–163.0 Mb) and R2 (20.8–128.2 Mb) congenic mice exhibited increases in body weight and abdominal fat weight and impaired glucose tolerance compared to SM/J mice. The R1 and R2 congenic analyses strongly suggested that the responsible genes existed in the overlapping genomic interval (69.6–128.2 Mb) between R1 and R2. In addition, studies using the newly established R1A congenic strain showed that the narrowed genomic region (69.6–75.4 Mb) affected not only obesity but also glucose tolerance. To search for candidate genes within the R1A genomic region, we performed exome sequencing analysis between SM/J and A/J mice and extracted 4 genes (Itga6, Zak, Gpr155, and Mtx2) with non-synonymous coding SNPs. These four genes might be candidate genes for type 2 diabetes caused by gene-gene interactions. This study indicated that one of the genes responsible for high-fat diet-induced diabetes exists in the 5.8 Mb genomic interval on mouse chromosome 2.     

阻塞型睡眠呼吸暂停低通气综合征与代谢综合征组分关系探讨

目的:探讨阻塞型睡眠呼吸暂停低通气综合征(OSAHS)与代谢综合征(MS)组分关系。方法:对我院2003年1月至2010年7月39例诊断为OSAHS住院患者进行回顾性调查,30例同期住院病人为对照组,均记录年龄、性别,测量身高、体重、血压,检测空腹血糖、血脂,分析OSAHS患者合并MS组分情况。结果:1.OSAHS组与对照组比较,体重指数(BMI)、血压、血清甘油三酯、总胆固醇、低密度脂蛋白胆固醇、载脂蛋白A1升高,高密度脂蛋白胆固醇降低(P<0.05);2.OSAHS组与对照组相比较,无MS组分比例低于对照组,差异有统计学意义(P<0.05);3.OSAHS组与对照组相比较,OSAHS组合并MS组分,包括BMI≥25Kg/m2,血脂紊乱的比例,均高于对照组,差异有统计学意义(P<0.05)。结论:OSAHS患者易合并代谢综合征组分。     

阻塞型睡眠呼吸暂停低通气综合征与代谢综合征组分关系探讨

目的：探讨阻塞型睡眠呼吸暂停低通气综合征（OSAHS）与代谢综合征（MS）组分关系。方法：对我院2003年1月至2010年7月39例诊断为0SAHS住院患者进行回顾性调查,30例同期住院病人为对照组,均记录年龄、性别,测量身高、体重、血压,检测空腹血糖、血脂,分析OSAHS患者合并MS组分情况。结果：1．OSAHS组与对照组比较,体重指数（BMI）、血压、血清甘油三酯、总胆固醇、低密度脂蛋白胆固醇、载脂蛋白Al升高,高密度脂蛋白胆固醇降低（P〈0．05）;2．OSAHS组与对照组相比较,无MS组分比例低于对照组,差异有统计学意义（P〈0．05）;3．OSAHS组与对照组相比较,OSAHS组合并MS组分,包括BMI〉25Kg／m2,血脂紊乱的比例,均高于对照组,差异有统计学意义（P〈0．05）。结论：OSAHS患者易合并代谢综合征组分。     

Cortical Metabolic Deficits in a Rat Model of Cholinergic Basal Forebrain Degeneration

Evidence indicates that the degeneration of basal forebrain cholinergic neurons may represent an important factor underlying the progressive cognitive decline characterizing Alzheimer’s disease (AD). However, the nature of the relationship between cholinergic depletion and AD is not fully elucidated. This study aimed at clarifying some aspects of the relation existing between deficits in cerebral energy metabolism and degeneration of cholinergic system in AD, by investigating the neuronal metabolic activity of several cortical areas after depletion of basal forebrain cholinergic neurons. In cholinergically depleted rats, we evaluated the neuronal metabolic activity by assaying cytochrome oxidase (CO) activity in frontal, parietal and posterior parietal cortices at four different time-points after unilateral injection of 192 IgG-saporin in the nucleus basalis magnocellularis. Unilateral depletion of cholinergic cells in the basal forebrain induced a bilateral decrease of metabolic activity in all the analyzed areas. Frontal and parietal cortices showed decreased metabolic activity even 3 days after the lesion, when the cholinergic degeneration was still incomplete. In posterior parietal cortex metabolic activity decreased only 7 days after the lesion. The possible molecular mechanisms underlying these findings were also investigated. Real-time PCR showed an increase of CO mRNA levels at 3, 7 and 15 days after the lesion both in frontal and parietal cortices, followed by normalization at 30 days. Western Blot analysis did not show any change in CO protein levels at any time-point after the lesion. Our findings support a link between metabolic deficit and cholinergic hypofunctionality characterizing AD pathology. The present model of cholinergic hypofunctionality provides a useful means to study the complex mechanisms linking two fundamental and interrelated phenomena characterizing AD from the early stages.     

饮食诱导代谢综合征小鼠模型的建立

目的建立以高脂纯化饲料诱导的、遗传背景和环境因素共同起作用的C57BL/6J小鼠代谢综合征（MS）模型,为研究营养因素与代谢综合征的关系提供周期较短、稳定性好、可重复性、与人类发病可比性高的动物模型。方法雄性3周龄C57BL/6J小鼠30只适应性喂养10d后随机分为2组,其中一组（10只）给予普通生长饲料（对照组）,另一组（20只）给予高脂纯化饲料（模型组）。喂养期间对空腹血糖（FBG）、体重进行连续监测,同时监测体重指数（BMI）、血清胰岛素（FINS）、血清甘油三脂（TG）、总胆固醇（TC）、高密度脂蛋白（HDL-C）、低密度脂蛋白（LDL-C）,实验期10周。实验结束时取内脏脂肪和肝脏称重,取肝胰做病理分析。结果分组喂养1周时,模型组小鼠体重出现显著性升高（P〈0.001）,并表现为中心型肥胖。4周时FBG显著性升高（P〈0.05）,5周时FINS开始升高但无显著性差异。8周时血清TC、HDL-C显著性升高（P〈0.001）,10周时TG、TC、HDL-C、LDL-C均升高（P〈0.01）。HE染色显示肝脏中度脂肪变,胰岛细胞无明显改变。结论单纯施以高脂饲料10周即可建立MS小鼠模型。并且该模型造模方法简单易行、周期较短、稳定性好、可重复性高,与人类MS自然发病过程类似,是MS较理想的动物模型。     

Factors Affecting Gender Differences in the Association between Health-Related Quality of Life and Metabolic Syndrome Components: Tehran Lipid and Glucose Study

Objective

Using structural equation modeling, this study is one of the first efforts aimed at assessing influential factors causing gender differences in the association between health-related quality of life (HRQoL) and metabolic syndrome.

Methods

A sample of 950 adults, from Tehran Lipid and Glucose Study were recruited for this cross sectional study in 2005–2007. Health-related quality of life was assessed using the Iranian version of SF-36. Metabolic syndrome components (MetSCs) and physical and mental HRQoL were considered as continuous latent constructs explaining the variances of their observed components. Structural equation modeling was performed to examine the association between the constructs of MetSCs and the physical and mental HRQoL within the two gender groups.

Results

Based on the primary hypothesis, MetSCs and HRQoL were fitted in a model. The negative effect of MetSCs on HRQoL was found to be significant only in the physical domain and only in women. The proportion of all the cardio-metabolic risk factors as well as subscales of physical HRQoL that have been explained via the two constructs of MetSCs and HRQoL, respectively, were significantly higher in women. Physical activity in both men (β = 3.19, p<0.05) and women (β = 3.94, p<0.05), age (β = -3.28, p<0.05), education (β = 2.63, p<0.05) only in women and smoking (β = 2.28, p<0.05) just in men, directly affected physical HRQoL. Regarding the mental domain, physical activity (β = 3.37, p<0.05) and marital status (β = 3.44, p<0.05) in women and age (β = 2.01, p<0.05) in men were direct effective factors. Age and education in women as well as smoking in men indirectly affected physical HRQoL via MetSCs.

Conclusion

Gender differences in the association between MetSCs and physical HRQoL could mostly be attributed to the different structures of both MetSCs and physical HRQoL constructs in men and women. Age and smoking are the most important socio-behavioral factors which could affect this gender-specific association in the mental domain.     

Genes on Rat Chromosomes 3, 5, 10, and 16 Are Linked With Facets of Metabolic Syndrome

WOKW (Wistar Ottawa Karlsburg W) rats develop metabolic syndrome closely resembling human disorder. In crossing studies between disease‐prone WOKW and disease‐resistant DA (Dark Agouti) rats, several quantitative trait loci (QTLs) were mapped. To prove the in vivo relevance of QTLs, congenic DA.WOKW rats, briefly termed DA.3aW, DA.3bW, DA.5W, DA.10W, and DA.16W, were generated by transferring chromosomal regions of WOKW chromosomes 3, 5, 10, and 16 onto DA genetic background. Male (n = 12) and female (n = 12) rats of each congenic strain and their parental strain DA were characterized for adiposity index (AI), serum leptin, and serum insulin as well as serum cholesterol and serum triglycerides as single facets of metabolic syndrome at the age of 30 weeks. The data showed a significant higher AI for male and female DA.3aW and female DA.16W compared with DA. Serum leptin was significantly elevated in male and female DA.3aW, DA.10W, and DA.16W rats in comparison with DA. Rats of both sexes of DA.10W and female DA.16W showed significantly elevated serum insulin in comparison to DA. Female rats of all congenics had significantly higher serum cholesterol compared with DA, while males did not differ. Finally, triglycerides were only elevated in male DA.16W. The results demonstrate an involvement of WOKW chromosomes 3, 5, 10, and 16 in developing facets of the metabolic syndrome.     

实验性X综合征大鼠模型的建立

目的　建立一种典型的X综合症动物模型。方法　雄性SD大鼠施行两肾一夹术后普通饲料喂养 4周 ,诱发肾性高血压 ,继以高果糖饲料喂养 4周 ,诱导建立X综合症模型。结果　术后 4周 ,大鼠仅出现收缩压升高 ,血糖、血脂未见明显改变。高果糖饲料喂养 4周后 ,大鼠出现高血糖、高胰岛素血症、胰岛素抵抗、高血压和高脂血症。结论　肾性高血压形成后高果糖饮食 1个月 ,可诱导SD大鼠出现典型的X综合症 ,为研究胰岛素抵抗及其伴随的心血管疾病提供了一种理想的动物模型。     

Genetic Analysis of a Rat Model of Aerobic Capacity and Metabolic Fitness

Aerobic capacity is a strong predictor of all-cause mortality and can influence many complex traits. To explore the biological basis underlying this connection, we developed via artificial selection two rat lines that diverge for intrinsic (i.e. inborn) aerobic capacity and differ in risk for complex disease traits. Here we conduct the first in-depth pedigree and molecular genetic analysis of these lines, the high capacity runners (HCR) and low capacity runners (LCR). Our results show that both HCR and LCR lines maintain considerable narrow-sense heritability (h²) for the running capacity phenotype over 28 generations (h² = 0.47 ± 0.02 and 0.43 ± 0.02, respectively). To minimize inbreeding, the lines were maintained by rotational mating. Pedigree records predict that the inbreeding coefficient increases at a rate of <1% per generation, ~37-38% slower than expected for random mating. Genome-wide 10K SNP genotype data for generations 5, 14, and 26 demonstrate substantial genomic evolution: between-line differentiation increased progressively, while within-line diversity deceased. Genome-wide average heterozygosity decreased at a rate of <1% per generation, consistent with pedigree-based predictions and confirming the effectiveness of rotational breeding. Linkage disequilibrium index r² decreases to 0.3 at ~3 Mb, suggesting that the resolution for mapping quantitative trait loci (QTL) can be as high as 2-3 cM. To establish a test population for QTL mapping, we conducted an HCR-LCR intercross. Running capacity of the F1 population (n=176) was intermediate of the HCR and LCR parentals (28 pairs); and the F2 population (n=645) showed a wider range of phenotypic distribution. Importantly, heritability in the F0-F2 pedigree remained high (h²~0.6). These results suggest that the HCR-LCR lines can serve as a valuable system for studying genomic evolution, and a powerful resource for mapping QTL for a host of characters relevant to human health.     

Components of Metabolic Syndrome as Risk Factors for Hearing Threshold Shifts

Background

Hearing loss was a common, chronically disabling condition in the general population and had been associated with several inflammatory diseases. Metabolic syndrome, which was associated with insulin resistance and visceral obesity, was considered a chronic inflammatory disease. To date, few attempts had been made to establish a direct relationship between hearing loss and metabolic syndrome. The aim of the present study was to investigate the relationship between metabolic syndrome and hearing loss by analyzing the data in the reports of the National Health and Nutrition Examination Survey 1999–2004.

Methods

This study included 2100 participants aged ≤ 65 years who enrolled in the National Health and Nutrition Examination Survey (1999–2004). We examined the relationship between the presence of different features of metabolic syndrome in the participants and their pure-tone air-conduction hearing thresholds, including low-frequency and high-frequency thresholds.

Results

After adjusting for potential confounders, such as age, medical conditions, and smoking status, the participants with more components of metabolic syndrome were found to have higher hearing thresholds than those with fewer components of metabolic syndrome (p < 0.05 for a trend). The low-frequency hearing threshold was associated with individual components of metabolic syndrome, such as abdominal obesity, high blood pressure, elevated triglycerides, and a low level of high-density lipoprotein cholesterol (HDL-C) (p < 0.05 for all parameters).

Conclusions

The results indicated that the presence of a greater number of components of metabolic syndrome was significantly associated with the hearing threshold in the US adult population. Among the components of metabolic syndrome, the most apparent association was observed between low HDL and hearing loss.     

Ghrelin Gene Variants Influence on Metabolic Syndrome Components in Aged Spanish Population

Background

The role of genetic variations within the ghrelin gene on cardiometabolic profile and nutritional status is still not clear in humans, particularly in elderly people.

Objectives

We investigated six SNPs of the ghrelin gene and their relationship with metabolic syndrome (MS) components.

Subjects and Methods

824 subjects (413 men/411 women, age 77.31±5.04) participating in the Mataró aging study (n = 310) and the Hortega study (n = 514) were analyzed. Anthropometric variables, ghrelin, lipids, glucose and blood pressure levels were measured, and distribution of SNPs -994CT (rs26312), -604GA (rs27647), -501AC (rs26802), R51Q (rs34911341), M72L (rs696217) and L90G (rs4684677) of the ghrelin gene evaluated. Genotypes were determined by multiplex PCR and SNaPshot minisequencing. MS (IDF criteria) was found in 54.9%.

Results

No association between any of the SNPs and levels of total fasting circulating ghrelin levels was found. C/A-A/A genotype of M72L was associated with increased risk of central obesity according to IDF criteria, while G/A-G/G genotypes of -604GA with reduced risk. A/A genotype of -501AC polymorphism was associated to decreased BMI. In relation to lipid profile, the same genotypes of -604GA were associated with increased total cholesterol and LDL-cholesterol and -501AC with reduced triglycerides. There were no associations with systolic or diastolic blood pressure levels or with hypertension, glucose levels or diabetes and ghrelin polymorphisms. However, G/G genotype of -604GA was associated with glucose >100 mg/dL. Haplotype analysis showed that only one haplotype is associated with increased risk of waist circumference and central obesity. The analysis of subjects by gender showed an important and different association of these polymorphisms regarding MS parameters.

Conclusion

Ghrelin gene variants -604GA, -501AC and M72L are associated with certain components of MS, in particular to BMI and lipid profile in elderly Spanish subjects.     

Isolation of Three Novel Rat and Mouse Papillomaviruses and Their Genomic Characterization

Despite a growing knowledge about the biological diversity of papillomaviruses (PV), only little is known about non-human PV in general and about PV mice models in particular. We cloned and sequenced the complete genomes of two novel PV types from the Norway rat (Rattus norvegicus; RnPV2) and the wood mouse (Apodemus sylvaticus; AsPV1) as well as a novel variant of the recently described MmuPV1 (originally designated as MusPV) from a house mouse (Mus musculus; MmuPV1 variant). In addition, we conducted phylogenetic analyses using a systematically representative set of 79 PV types, including the novel sequences. As inferred from concatenated amino acid sequences of six proteins, MmuPV1 variant and AsPV1 nested within the Beta+Xi-PV super taxon as members of the Pi-PV. RnPV2 is a member of the Iota-PV that has a distant phylogenetic position from Pi-PV. The phylogenetic results support a complex scenario of PV diversification driven by different evolutionary forces including co-divergence with hosts and adaptive radiations to new environments. PV types particularly isolated from mice and rats are the basis for new animal models, which are valuable to study PV induced tumors and new treatment options.     

Congenic mapping of a blood pressure QTL on Chromosome 16 of Dahl rats

A Chromosome (Chr) 16 segment of the Dahl salt-sensitive (S) rat was shown by linkage to contain a blood pressure (BP) quantitative trait locus (QTL). To verify and further narrow down the region harboring the QTL, we made two congenic strains by replacing two segments of the S rats with the homologous segments of the Lewis (LEW) rats. The construction of these congenic strains was facilitated by a genome-wide marker screening. The two congenic strains contained a segment in common, and BPs of both were significantly lower than that of the S strain. Consequently, a BP QTL could be localized to the overlapping region of about 49.4 centiRay (cR) including the telomere on a radiation hybrid map. Heart weights, left and right ventricular weights, kidney weights, and aortic weights over length were all significantly decreased in the congenic strains compared with the S strain. Thus, there appeared to exist an association between the effects of the QTL on BP and on cardiac, renal, and vascular hypertrophy.     

Clustering of the Metabolic Syndrome Components in Adolescence: Role of Visceral Fat

Visceral fat (VF) promotes the development of metabolic syndrome (MetS), which emerges as early as in adolescence. The clustering of MetS components suggests shared etiologies, but these are largely unknown and may vary between males and females. Here, we investigated the latent structure of pre-clinical MetS in a community-based sample of 286 male and 312 female adolescents, assessing their abdominal adiposity (VF) directly with magnetic resonance imaging. Principal component analysis of the five MetS-defining variables (VF, blood pressure [BP], fasting serum triglycerides, HDL-cholesterol and glucose) identified two independent components in both males and females. The first component was sex-similar; it explained >30% of variance and was loaded by all but BP variables. The second component explained >20% of variance; it was loaded by BP similarly in both sexes but additional loading by metabolic variables was sex-specific. This sex-specificity was not detected in analyses that used waist circumference instead of VF. In adolescence, MetS-defining variables cluster into at least two sub-syndromes: (1) sex-similar metabolic abnormalities of obesity-induced insulin resistance and (2) sex-specific metabolic abnormalities associated with BP elevation. These results suggest that the etiology of MetS may involve more than one pathway and that some of the pathways may differ between males and females. Further, the sex-specific metabolic abnormalities associated with BP elevation suggest the need for sex-specific prevention and treatment strategies of MetS.