Transcriptomic analysis of mRNA of inguinal white adipose tissues from ZSF1 lean and obese rats, ZSF1 obese rats under calorie restriction, as well as ZSF1 obese rats dosed with Cmpd1.
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ABSTRACT: The analysis is performed to understand the role of Cmpd1 in modulating transcritomic profiles in the inguinal white adipose tissues of ZSF1 rats.
Project description:Transcriptomic analysis of mRNA of inguinal white adipose tissues from ZSF1 lean and obese rats, ZSF1 obese rats under calorie restriction, as well as ZSF1 obese rats dosed with Cmpd1.
Project description:BackgroundChildhood obesity is an important early predictor of adult obesity and associated comorbidities. Common forms of obesity are underpinned by both environmental and genetic factors. However, the rising prevalence of obesity in genetically stable populations strongly suggests that contemporary lifestyle is a premier factor to the disease. In pediatric population, the current treatment/prevention options for obesity are lifestyle interventions such as caloric restriction (CR) and increase physical activity. In obese individuals, CR improves many metabolic parameters in peripheral tissues. Little is known about the effect of CR on the hypothalamus. This study aimed to assess the effect of CR on hypothalamic metabolic gene expression of young obese- and lean-prone animals.MethodsMale juvenile JCR:LA-cp obese-prone rats were freely fed (Obese-FF) or pair fed (Obese-FR) to lean-prone, free-feeding animals (Lean-FF). A group of lean-prone rats (Lean-FR) were matched for relative average degree of CR to Obese-FR rats.ResultsIn free-feeding conditions, obese-prone rats consumed more energy than lean-prone rats (P<0.001) and showed greater increases in body weight, fat mass, plasma glucose, insulin and lipids (P<0.01). These metabolic differences were associated with alterations of feeding-related neuropeptides expression in the hypothalamus, as well as pro-inflammatory cytokines and oxidative stress markers. When submitted to the same degree of CR, the two genotypes responded differently; hypothalamic inflammatory and oxidative stress gene expression was improved in Obese-FR, while it was worsened in Lean-FR rats.ConclusionsWe demonstrate in JCR rats that the metabolic and inflammatory response of the brain to CR is genotype dependent.
Project description:AimsTo investigate the influence of the dose in the FITC-Dextran 4kDa (FD-4) permeability test in an obese mouse model, we tested the bodyweight dose regimen and a lean body mass-based dose regimen in high fat diet (HFD) mice and low fat diet (LFD) mice. We hypothesized that the FD-4 permeation result would be dose-dependent.MethodsThe two dose regimens were compared in HFD and LFD mice. Furthermore, we conducted a dose-response study to test the effect of a low or high dose of FD-4 in weight-stratified lean mice. Gene analysis of tight junctions was also carried out.ResultsThe FD-4 intestinal permeability test was dose-dependent as we found a significant increase in plasma levels of FD-4 in obese mice with the bodyweight dose regimen. However, this difference was not detectable with the lean body mass dose regimen, even with variability-adjusted group sizes. However, the qPCR analysis revealed a decrease in tight junction gene expression in obese mice. Furthermore, we found a dose-dependent significant increase in FD-4 measured in plasma samples in lean mice. No significant difference in intestinal weight was observed between lean and obese mice.ConclusionEvaluation of the intestinal permeability by FD-4 with the typical bodyweight dose regimen in obese mice will be confounded by the significant difference in dose given when compared to a lean control group. If the test dose is based on lean body mass, no significant difference in intestinal permeability is observed, even with large group sizes. Furthermore, we showed a dose-dependent difference in plasma FD-4 levels in lean mice. Therefore, we conclude that the dose should be based on lean body mass for the FD-4 permeability test if mice with considerable obesity differences are to be compared or to use another test with fixed doses.
Project description:Obesity has been on the rise in the US and worldwide for the last several decades. Obesity has been associated with chronic disease development, such as certain types of cancer, type 2 diabetes, cardiovascular disease, and liver diseases. Previously, we reported that obesity promotes DMBA-induced mammary tumor development using the obese Zucker rat model. The intestinal microbiota is composed of a diverse population of obligate and facultative anaerobic microorganisms, and these organisms carry out a broad range of metabolic activities. Obesity has been linked to changes in the intestinal microbiota, but the composition of the bacterial populations in lean and obese Zucker rats has not been carefully studied. Therefore, the objective of this study was to determine the effects of obesity on the gut microbiota in this model. Lean and obese female Zucker rats (n = 16) were fed an AIN-93G-like diet for 8 weeks. Rats were weighed twice weekly, and fecal samples were collected at the beginning and end of the experiment. 16S rRNA gene sequencing was used to evaluate the composition of the fecal bacterial populations. At the outset of the study, the lean rats exhibited much lower ratios of the Firmicutes to Bacteroidetes phyla than the obese rats, but after 60 days, this ratio in the lean rats exceeded that of the obese. This shift was associated with reductions in the Bacteroidaceae, S24-7 and Paraprevotellaceae families in the lean rats. Obese rats also showed increased levels of the genus Akkermansia at day 60. PCoA plots of beta diversity showed clustering of the different test groups, indicating clear differences in intestinal microbiota populations associated with both the time point of the study and the lean or obese status in the Zucker rat model for obesity.
Project description:BackgroundObesity associates with low-grade inflammation and adipose tissue remodeling. Using sensitive high-throughput protein arrays we here investigated adipose tissue cytokine and angiogenesis-related protein profiles from obese and lean mice, and in particular, the influence of calorie restriction (CR).MethodsTissue samples from visceral fat were harvested from obese mice fed with a high-fat diet (60% of energy), lean controls receiving low-fat control diet as well as from obese and lean mice kept under CR (energy intake 70% of ad libitum intake) for 50 days. Protein profiles were analyzed using mouse cytokine and angiogenesis protein array kits.ResultsIn obese and lean mice, CR was associated with 11.3% and 15.6% reductions in body weight, as well as with 4.0% and 4.6% reductions in body fat percentage, respectively. Obesity induced adipose tissue cytokine expressions, the most highly upregulated cytokines being IL-1ra, IL-2, IL-16, MCP-1, MIG, RANTES, C5a, sICAM-1 and TIMP-1. CR increased sICAM-1 and TIMP-1 expression both in obese and lean mice. Overall, CR showed distinct effects on cytokine expressions; in obese mice CR largely decreased but in lean mice increased adipose tissue cytokine expressions. Obesity was also associated with increased expressions of angiogenesis-related proteins, in particular, angiogenin, endoglin, endostatin, endothelin-1, IGFBP-3, leptin, MMP-3, PAI-1, TIMP-4, CXCL16, platelet factor 4, DPPIV and coagulation factor III. CR increased endoglin, endostatin and platelet factor 4 expressions, and decreased IGFBP-3, NOV, MMP-9, CXCL16 and osteopontin expressions both in obese and lean mice. Interestingly, in obese mice, CR decreased leptin and TIMP-4 expressions, whereas in lean mice their expressions were increased. CR decreased MMP-3 and PAI-1 only in obese mice, whereas CR decreased FGF acidic, FGF basic and coagulation factor III, and increased angiogenin and DPPIV expression only in lean mice.ConclusionsCR exerts distinct effects on adipocyte cytokine and angiogenesis profiles in obese and lean mice. Our study also underscores the importance of angiogenesis-related proteins and cytokines in adipose tissue remodeling and development of obesity.
Project description:This study evaluated the intestinal effects of alkalinized filtered water in lean and obese adult Zucker rats. For 3 months, 12-week-old rats consumed either tap water or filtered alkalinized tap water from Madrid city. Weight gain was monitored, changes in metabolism were evaluated by indirect calorimetry, and total antioxidant capacity and levels of inflammatory mediators were measured in plasma. Feces were collected, their microbial composition was analyzed and histological analysis of the small and large intestine was performed, assessing the general state of the mucosa (MUC2), the inflammatory state (F4/80) and the presence of oxidative modifications in protein 4-Hydroxynonenal (4-HNE) by immunofluorescence (IF) and immunohistochemistry (IHC). The results obtained showed that the consumption of alkalinized filtered water improved the composition of the intestinal microbiome and the state of the intestinal mucosa, reducing both local and systemic inflammation and the level of oxidative stress. These changes were accompanied by a better maintenance of the oxidative status in rats. No differences were observed in antioxidant capacity nor in weight gain. The incorporation of probiotics in the diet had a significant impact on the microbiome. These effects were indicative of an improvement in general metabolic, oxidative and inflammatory status.
Project description:We asked if miRNAs are involved in PRDM16 protein expression. Thus microarray was employed with inguinal adipose tissues from contol, fasted and cold exposure C57BL/6J male mice In this dataset, we include all the miRNA expression data obtained from dissected mouse inguinal adipose tissues from control, fasted and cold exposure mice.
Project description:Perivascular adipose tissue (PVAT) is recognized as a paracrine organ that controls vascular function. One of the early data demonstrated PVAT from male Sprague-Dawley rats altered aortic vascular reactivity [1]. Subsequent studies have suggested PVAT mediated vascular reactivity is impaired in a variety of vascular beds with animal models of metabolic syndrome [2]. Findings in these experimental animals are generally reported by only male data. Here we report the new data on the effects of PVAT on the aortic reactivity of female lean zucker rats (LZR) and obese zucker rats (OZR). The data presented here is related to a recent manuscript entitled "Aortic dysfunction in metabolic syndrome mediated by perivascular adipose tissue TNFα- and NOX2-dependent pathway" [3] which demonstrated PVAT from male obese Zucker rats (OZR) impaired endothelial function of aorta which is associated with altered PVAT inflammatory signaling.
Project description:Obesity is risk factor for development of fatty liver. Analysis of altered gene expression gives better understading about the mechanisms involved/alterted in the development of obesity-induced fattyliver in this new obese rat model. We used Microarrays to delinate the alted gene expression in liver of WNIN/Ob obese rats