Perivascular adipose tissue mediated aortic reactivity data: Female lean and obese Zucker rats.
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ABSTRACT:
SUBMITTER: Tilley MA
PROVIDER: S-EPMC7044513 | biostudies-literature |
REPOSITORIES: biostudies-literature
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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.
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Project description:Using two-dimensional electrophoresis on total extracts of adipose tissue from young lean (Fa/fa) and obese (fa/fa) Zucker rats, we have investigated the existence of early events at the protein level, before obvious obesity. Our results indicate that the two genotypes do not differ at 3 days of age in terms of polypeptide pattern. By 7 days of age, two polypeptides are transiently repressed in the fatty genotype, leading us to suggest their potential involvement in the onset of obesity. However, most of the differences between the lean and obese rats are detected at 30 days of age, characterized by an increase in the accumulation of several peptides in the adipose tissue of obese rats, in good agreement with the multiple biochemical changes previously identified at this stage of the disease. These results present evidence of new peptides that may be of interest in the study of the obesity syndrome.
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Project description:Central obesity is associated with low-grade inflammation that promotes type 2 diabetes and cardiovascular disease in obese individuals. The 12- and 5-lipoxygenase (12-LO and 5-LO) enzymes have been linked to inflammatory changes, leading to the development of atherosclerosis. 12-LO has also been linked recently to inflammation and insulin resistance in adipocytes. We analyzed the expression of LO and proinflammatory cytokines in adipose tissue and adipocytes in obese Zucker rats, a widely studied genetic model of obesity, insulin resistance, and the metabolic syndrome. mRNA expression of 12-LO, 5-LO, and 5-LO-activating protein (FLAP) was upregulated in adipocytes and adipose tissue from obese Zucker rats compared with those from lean rats. Concomitant with increased LO gene expression, the 12-LO product 12-HETE and the 5-LO products 5-HETE and leukotriene B4 (LTB4) were also increased in adipocytes. Furthermore, upregulation of key proinflammatory markers interleukin (IL)-6, TNFα, and monocyte chemoattractant protein-1 were observed in adipocytes isolated from obese Zucker rats. Immunohistochemistry indicated that the positive 12-LO staining in adipose tissue represents cells in addition to adipocytes. This was confirmed by Western blotting in stromal vascular fractions. These changes were in part reversed by the novel anti-inflammatory drug lisofylline (LSF). LSF also reduced p-STAT4 in visceral adipose tissue from obese Zucker rats and improved the metabolic profile, reducing fasting plasma glucose and increasing insulin sensitivity in obese Zucker rats. In 3T3-L1 adipocytes, LSF abrogated the inflammatory response induced by LO products. Thus, therapeutic agents reducing LO or STAT4 activation may provide novel tools to reduce obesity-induced inflammation.
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Project description:RationaleMaternal obesity pre-programmes offspring to develop obesity and associated cardiovascular disease. Perivascular adipose tissue (PVAT) exerts an anti-contractile effect on the vasculature, which is reduced in hypertension and obesity.ObjectiveThe objective of this study was to determine whether maternal obesity pre-programmes offspring to develop PVAT dysfunction in later life.MethodsFemale Sprague-Dawley rats were fed a diet containing 10% (control) or 45% fat (high fat diet, HFD) for 12 weeks prior to mating and during pregnancy and lactation. Male offspring were killed at 12 or 24 weeks of age and tension in PVAT-intact or -denuded mesenteric artery segments was measured isometrically. Concentration-response curves were constructed to U46619 and norepinephrine.ResultsOnly 24-week-old HFD offspring were hypertensive (P<0.0001), although the anti-contractile effect of PVAT was lost in vessels from HFD offspring of each age. Inhibition of nitric oxide (NO) synthase with 100 μM l-NMMA attenuated the anti-contractile effect of PVAT and increased contractility of PVAT-denuded arteries (P<0.05, P<0.0001). The increase in contraction was smaller in PVAT-intact than PVAT-denuded vessels from 12-week-old HFD offspring, suggesting decreased PVAT-derived NO and release of a contractile factor (P<0.07). An additional, NO-independent effect of PVAT was evident only in norepinephrine-contracted vessels. Activation of AMP-activated kinase (with 10 μM A769662) was anti-contractile in PVAT-denuded (P<0.0001) and -intact (P<0.01) vessels and was due solely to NO in controls; the AMPK effect was similar in HFD offspring vessels (P<0.001 and P<0.01, respectively) but was partially NO-independent.ConclusionsThe diminished anti-contractile effects of PVAT in offspring of HFD dams are primarily due to release of a PVAT-derived contractile factor and reduced NO bioavailability.
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Project description:OBJECTIVE:The effects of coronary perivascular adipose tissue (PVAT) on vasomotor tone are influenced by an obese phenotype and are distinct from other adipose tissue depots. The purpose of this investigation was to examine the effects of lean and obese coronary PVAT on end-effector mechanisms of coronary vasodilation and to identify potential factors involved. APPROACH AND RESULTS:Hematoxylin and eosin staining revealed similarities in coronary perivascular adipocyte size between lean and obese Ossabaw swine. Isometric tension studies of isolated coronary arteries from Ossabaw swine revealed that factors derived from lean and obese coronary PVAT attenuated vasodilation to adenosine. Lean coronary PVAT inhibited K(Ca) and KV7, but not KATP channel-mediated dilation in lean arteries. In the absence of PVAT, vasodilation to K(Ca) and KV7 channel activation was impaired in obese arteries relative to lean arteries. Obese PVAT had no effect on K(Ca) or KV7 channel-mediated dilation in obese arteries. In contrast, obese PVAT inhibited KATP channel-mediated dilation in both lean and obese arteries. The differential effects of obese versus lean PVAT were not associated with changes in either coronary KV7 or K(ATP) channel expression. Incubation with calpastatin attenuated coronary vasodilation to adenosine in lean but not in obese arteries. CONCLUSIONS:These findings indicate that lean and obese coronary PVAT attenuates vasodilation via inhibitory effects on vascular smooth muscle K(+) channels and that alterations in specific factors such as calpastatin are capable of contributing to the initiation or progression of smooth muscle dysfunction in obesity.
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Project description:Interactions between macrophages and adipocytes influence both metabolism and inflammation. Obesity-induced changes to macrophages and adipocytes lead to chronic inflammation and insulin resistance. This paper reviews the various functions of macrophages in lean and obese adipose tissue and how obesity alters adipose tissue macrophage phenotypes. Metabolic disease and insulin resistance shift the balance between numerous pro- and anti-inflammatory regulators of macrophages and create a feed-forward loop of increasing inflammatory macrophage activation and worsening adipocyte dysfunction. This ultimately leads to adipose tissue fibrosis and diabetes. The molecular mechanisms underlying these processes have therapeutic implications for obesity, metabolic syndrome, and diabetes.
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Project description:RationaleAlthough obstructive sleep apnea is strongly associated with obesity, we have little understanding of how obesity may alter the mechanical properties of the pharynx and the role of obesity in the pathogenesis of sleep apnea.ObjectivesThe overall objective of this study was to determine the effect of obesity on pharyngeal airway size and pharyngeal wall tissue strain in lean and obese Zucker rats.MethodsRespiratory-gated magnetic resonance imaging with noninvasive tissue tagging was performed in anesthetized, spontaneously breathing lean (n = 9) and obese (n = 9) Zucker rats. Images acquired during expiration and inspiration of the rostral, mid-, and caudal pharynx were analyzed for airway size and pharyngeal wall tissue strain, using planimetry, optical flow, and finite element analyses. Differences in cross-sectional airway area, lateral and anteroposterior airway diameters, and tissue strain (stretch, compression, and direction of stretch) in the lateral and ventral pharyngeal walls were compared by analysis of variance (significance at p < 0.05).Measurements and main resultsCompared with their lean littermates, obese rats had the following significant findings: reduced pharyngeal airway cross-sectional area during inspiration and expiration, smaller increases in airway area during inspiration, and decreased lateral airway dilation during inspiration. Tissue strain in the pharyngeal walls showed no significant differences between obese and lean rats.ConclusionsThese findings suggest that obesity results in a mechanical abnormality that decreases pharyngeal airway size and prevents a normal airway response to a given change in pharyngeal wall tissue strain.
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