Red raspberry (Rubus idaeus) consumption restores the impaired vasoconstriction and vasorelaxation in the aorta of the obese zucker rat, a model of the metabolic syndrome

2020 ◽  
pp. 1-13
Author(s):  
Natalie E. VandenAkker ◽  
Stefano Vendrame ◽  
Panagiotis Tsakiroglou ◽  
Dorothy Klimis-Zacas
Keyword(s):  
Metabolic Syndrome ◽  
Vascular Function ◽  
Vascular Tone ◽  
Rubus Idaeus ◽  
Relaxation Response ◽  
Zucker Rat ◽  
Red Raspberry ◽  
The Metabolic Syndrome ◽  
Obese Zucker Rat ◽  
Pre Treatment

Metabolic Syndrome (MetS) increases the risk of cardiovascular disease. Whole red raspberry (WRR) consumption on vascular function was investigated in the obese Zucker rat (OZR), model of MetS. Male OZR and their lean littermates (LZR) were placed on a control (C) or an 8% w/w WRR-enriched diet for 8 weeks. Phenylephrine (Phe)-induced vasoconstriction and acetylcholine (Ach)-induced vasorelaxation were measured in aortic rings in the presence or absence of L-N-monomethyl-arginine (L-NMMA) and mefenamic acid (MFA). Phe-induced vasoconstriction was lower in the OZR-C compared to LZR-C (p <  0.05). The WRR diet partially restored aortic response in the OZR-WRR aorta (p <  0.05) compared to OZR- C. The OZR-WRR group pre-treated with L-NMMA increased compared to OZR-C (p <  0.05). Pre-treatment with L-NMMA, maximal relaxation response was higher in the OZR compared to the LZR (p <  0.05). With L-NMMA, maximal relaxation response in OZR-WRR (p <  0.05) was lower compared to the OZR-C. Prostacyclin I2 concentration was higher in the OZR compared to the LZR (p <  0.05) and was attenuated in the OZR-WRR (p <  0.05). Aortic expression of eNOS and COX-2 were downregulated in the OZR-WRR (p <  0.05). In conclusion, WRR restores the impaired vascular tone of the OZR by enhancing Phe-induced vasoconstriction and attenuating Ach-induced vasorelaxation.

Whole Red Raspberry (Rubus idaeus)-Enriched Diet Is Hepatoprotective in the Obese Zucker Rat, a Model of the Metabolic Syndrome

2020 ◽  
Author(s):  
Natalie E. VandenAkker ◽  
Stefano Vendrame ◽  
Panagiotis Tsakiroglou ◽  
Marissa McGilvrey ◽  
Dorothy Klimis-Zacas
Keyword(s):  
Metabolic Syndrome ◽  
Rubus Idaeus ◽  
Zucker Rat ◽  
Red Raspberry ◽  
The Metabolic Syndrome ◽  
Obese Zucker Rat

Vascular function in the metabolic syndrome and the effects on skeletal muscle perfusion: lessons from the obese Zucker rat

2006 ◽  
Vol 42 ◽  
pp. 145-160 ◽  
Author(s):  
Jefferson C. Frisbee ◽  
Michael D. Delp
Keyword(s):  
Metabolic Syndrome ◽  
Vascular Function ◽  
Human Condition ◽  
Therapeutic Interventions ◽  
Western Society ◽  
Zucker Rat ◽  
Metabolic Demand ◽  
Muscle Perfusion ◽  
The Metabolic Syndrome ◽  
Obese Zucker Rat

The increased prevalence of obesity in Western society has been well established for many years, and with this trend, the prevalence of other associated pathologies including insulin resistance, dyslipidaemia, hypertension and the genesis of a proinflammatory and prothrombotic environment within individuals is also rapidly increasing, resulting in a condition known as the~metabolic syndrome. From a physiological perspective, one of the most severe consequences of the metabolic syndrome is a progressive inability of the cardiovascular system to adequately perfuse tissues and organs during either elevated metabolic demand and, if sufficiently severe, under basal levels of demand. For the study of the metabolic syndrome, the OZR (obese Zucker rat) represents an important tool in this effort, as the metabolic syndrome in these animals results from a chronic hyperphagia, and thus can be an excellent representation of the human condition. As in afflicted humans, OZR experience an attenuated functional and reactive hyperaemia, and can ultimately experience an ischaemic condition in their skeletal muscles at rest. The source of this progressive ischaemia appears to lie at multiple sites, as endothelium-dependent vasodilator responses are strongly impaired in OZR, and specific constrictor processes (e.g. adrenergic tone) may be enhanced. Whilst these active processes may contribute to a reduction in blood flow under resting conditions or with mild elevations in metabolic demand, an evolving structural alteration to individual microvessels (reduced distensibility) and microvascular networks (reduced microvessel density) also develop and may act to constrain perfusion at higher levels of metabolic demand. Given that constrained muscle perfusion in the metabolic syndrome appears to reflect a highly integrated, multi-faceted effect in OZR, and probably in humans as well, therapeutic interventions must be designed to address each of these contributing elements.

scholarly journals Red raspberry (Rubus idaeus) consumption attenuates inflammation in the obese Zucker rat, a model of the Metabolic Syndrome (OR24-01-19)

2019 ◽  
Vol 3 (Supplement_1) ◽  
Author(s):  
Natalie VandenAkker ◽  
Stefano Vendrame ◽  
Dorothy Klimis-Zacas
Keyword(s):  
Metabolic Syndrome ◽  
Body Weight ◽  
Food Consumption ◽  
Zucker Rat ◽  
Red Raspberry ◽  
High Blood Glucose ◽  
The Metabolic Syndrome ◽  
Obese Zucker Rat ◽  
Tnf Α ◽  
Inflammatory State

Abstract Objectives Metabolic syndrome (MetS) is a major public health problem that is escalating quickly globally. MetS is defined as a combination of obesity, high blood pressure, high blood glucose, low high-density lipoprotein and high cholesterol resulting in a pro-thrombotic and pro-inflammatory state. This study investigated the effect of whole red raspberry (WRR) consumption on inflammation in the obese Zucker rat (OZR), a model of the MetS. Methods At 8 weeks of age, male OZR (n = 16) and their lean littermates (LZR) (n = 16) were placed on a control (C) or an 8% w/w WRR-enriched diet for 8 weeks. Body weight and daily food consumption was measured. Circulating levels of inflammatory cytokines and their gene expression in the liver and adipose tissue (AT) were evaluated. Results No significant differences were observed in body weight or food consumption between diet groups. Consumption of WRR significantly reduced the plasma level of pro-inflammatory molecule, C-reactive protein (CRP) in the OZR compared to OZR-C (1024 ± 108.74 μg/ml vs 4250 ± 1120.12 μg/ml, p < 0.05) respectively. Plasma levels of interleukin-6 (IL-6), a pro-inflammatory cytokine decreased in the OZR consuming a WRR diet compared to the OZR-C (20.69 ± 1.41 pg/ml vs 50.50 ± 3.66 pg/ml, p < 0.0001) respectively. Following the consumption of WRR, the expression of pro-inflammatory molecules IL-6 and tumor necrosis factor-alpha (TNF-α) in the OZR significantly down-regulated (p < 0.01 and p < 0.05) respectively, in the AT. The expression of pro-inflammatory markers IL-6, TNF-α, and nuclear factor kappa-B (NF-ΚB) also significantly down-regulated (p < 0.01, p < 0.0001 and p < 0.05) respectively, following the consumption of WRR in the OZR compared to the OZR-C. Conclusions The results from the present study demonstrate that daily consumption of WRR improves the pro-inflammatory state associated with MetS. Funding Sources National Processed Raspberry Council USDA National Institute of Food and Agriculture Hatch FutureCeuticals (Momence, IL USA)

Habitual Physical Exercise Improves Macrophage IL-6 and TNF-α Deregulated Release in the Obese Zucker Rat Model of the Metabolic Syndrome

2011 ◽  
Vol 18 (2) ◽  
pp. 123-130 ◽  
Author(s):  
Leticia Martín-Cordero ◽  
Juan José García ◽  
María Dolores Hinchado ◽  
Elena Bote ◽  
Rafael Manso ◽  
...  
Keyword(s):  
Metabolic Syndrome ◽  
Physical Exercise ◽  
Rat Model ◽  
Zucker Rat ◽  
The Metabolic Syndrome ◽  
Obese Zucker Rat ◽  
Tnf Α

Wild blueberry (Vaccinium angustifolium) consumption improves inflammatory status in the obese Zucker rat model of the metabolic syndrome

2013 ◽  
Vol 24 (8) ◽  
pp. 1508-1512 ◽  
Author(s):  
Stefano Vendrame ◽  
Allison Daugherty ◽  
Aleksandra S. Kristo ◽  
Patrizia Riso ◽  
Dorothy Klimis-Zacas
Keyword(s):  
Metabolic Syndrome ◽  
Rat Model ◽  
Zucker Rat ◽  
Vaccinium Angustifolium ◽  
The Metabolic Syndrome ◽  
Inflammatory Status ◽  
Obese Zucker Rat ◽  
Wild Blueberry

Abstract 3672: Loss of Perivascular Adipocyte Paracrine Function Leads to Increased Vascular Tone and Glucose Intolerance in Hypertension

Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Kaivan Khavandi ◽  
Adam Greenstein ◽  
Sarah Withers ◽  
Kazuhiko Sonoyama ◽  
Sarah Lewis ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Metabolic Syndrome ◽  
Adipose Tissue ◽  
Vascular Tone ◽  
Tnf Alpha ◽  
Perivascular Adipose Tissue ◽  
The Metabolic Syndrome ◽  
Adipocyte Cell ◽  
Therapeutic Opportunity

In order to investigate the contribution of perivascular adipose tissue (PVAT) to arterial function, a total of 55 small arteries harvested from 35 skin biopsies of patients with Metabolic Syndrome and matched controls were mounted as ring preparations in a wire myograph. Contractility to cumulative doses of Norepinephrine in the presence or absence of PVAT showed an anticontractile effect in arteries from healthy volunteers (p=0.009), which was lost in patients with Metabolic Syndrome. Bioassay studies confirmed that PVAT releases a hydrophilic anticontractile factor in health, which is absent in obesity. Using a soluble fragment of the human Type 1 receptor, we identified that the anticontractile factor was adiponectin, which is the sole mediator of vasodilation, acting by increasing endothelial bioavailability of nitric oxide. Significant endothelial dysfunction was observed in patients with Metabolic Syndrome (p<0.001). Quantitative image analysis of adipose tissue revealed significantly increased adipocyte cell size in patients with Metabolic Syndrome, compared with healthy controls (p<0.006). There was immunohistochemical evidence of inflammation with upregulation of TNF-alpha receptor 1 in these patients (p<0.001). Application of exogenous TNF-alpha abolished the anticontractile effect of PVAT by reducing adiponectin bioavailability. Oxidative stress also induced by cytokines TNF-alpha and IL-6 but not IL-1, reduced adiponectin production from PVAT and increased basal tone. When the obese microenvironment was replicated in vitro by inflicting hypoxia on PVAT, adiponectin activity was lost but then rescued by incubation with cytokine antagonists. Further application of the adiponectin receptor fragment abolished PVAT relaxation. We conclude that in healthy arteries, PVAT releases adiponectin which reduces vascular tone. In obesity, this is lost by a cascade of adipocyte hypertrophy, hypoxia, inflammation and oxidative stress. The resulting vasoconstriction contributes to hypertension, hypertriglyceridaemia and insulin resistance. Direct targeting of adiponectin release from PVAT therefore provides a novel therapeutic opportunity in the Metabolic Syndrome.

Abstract 3203: The role of Neprilysin in the Development of Insulin Resistance, Type 2 Diabetes and Cardiovascular Disease

Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Kristina F Standeven ◽  
Angela M Carter ◽  
Anthony J Balmforth ◽  
Stephen B Wheatcroft ◽  
Nigel M Hooper ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Metabolic Syndrome ◽  
Vascular Function ◽  
Animal Studies ◽  
Obese Mice ◽  
Human Adipocytes ◽  
The Metabolic Syndrome ◽  
Mesenteric Fat ◽  
Order Of Magnitude ◽  
Average Gene

Neprilysin (NEP) cleaves several bioactive peptides involved in the regulation of vascular function. In human microvascular endothelial cells, fatty acids and glucose increase NEP activity, and inhibition of NEP in animal studies results in increased insulin sensitivity, suggesting that NEP may be related to the metabolic syndrome. We tested this hypothesis in cell, animal and human based models. Microarray analysis of mRNA expression in differentiated human adipocytes (Affymetrix Human Genome U133 Plus 2.0 arrays) showed NEP expression to be an order of magnitude higher than the average gene signal, suggesting that human adipocytes express high endogenous levels of NEP mRNA. Real time PCR confirmed high levels of NEP mRNA in preadipocytes which increased 28 fold during differentiation and reached levels equivalent to the endogenous control, GAPDH, by 14 days. We created a diet induced model of obesity by feeding male C57BL/6J mice a high-fat diet, which resulted in decreased glucose tolerance and insulin resistance in obese mice. Plasma NEP levels measured after 15 weeks of feeding were significantly higher in obese mice (1642 [± 529]) pg/μl) compared to lean mice (820 [± 487] pg/μl) (p < 0.01). NEP levels increased 4- and 9-fold in epididymal and mesenteric fat in obese, compared to lean, mice. In a study of 318 healthy white European males, plasma NEP measured by activity assay was significantly higher in subjects with the metabolic syndrome (MetS) and levels increased progressively with increasing number of MetS components, being ~8-fold higher in those with 5 MetS components compared with those with none. NEP correlated with insulin, HOMA and BMI in all subjects. In conclusion, we have generated cell, murine and human data which suggest that NEP may have an important role in cardio-metabolic risk associated with insulin resistance, with the adipocyte as a major source of NEP. These findings indicate that NEP is a novel adipokine that links insulin resistance to vascular risk.

scholarly journals Metabolic syndrome: what is it and what are the implications?

2005 ◽  
Vol 64 (3) ◽  
pp. 349-357 ◽  
Author(s):  
D. I. Shaw ◽  
W. L. Hall ◽  
C. M. Williams
Keyword(s):  
Type 2 Diabetes ◽  
Metabolic Syndrome ◽  
Abdominal Obesity ◽  
Vascular Function ◽  
Hdl Cholesterol ◽  
The Metabolic Syndrome ◽  
Obesity And Overweight ◽  
Increased Risk ◽  
Diet And Exercise

Obesity and overweight are linked with a cluster of metabolic and vascular disorders that have been termed the metabolic syndrome. Although there is not yet a universally-accepted set of diagnostic criteria, most expert groups agree that the syndrome is characterised by impaired insulin sensitivity and hyperglycaemia, dyslipidaemia (elevated blood triacyglycerols with depressed HDL-cholesterol), abdominal obesity and hypertension. Based on existing published criteria estimates suggest that the syndrome affects a substantial percentage of the middle-aged and elderly populations of most European countries (10–20%) and confers increased risk of type 2 diabetes (2–8.8-fold) and CVD (1.5–6-fold), as well as having a marked effect on morbidity. Although the pathophysiology is incompletely understood, insulin resistance and abdominal obesity are central to subsequent abnormalities in circulating glucose and lipoproteins, and vascular function that lead to type 2 diabetes, atherosclerosis and CVD. The link between metabolic syndrome, type 2 diabetes and CVD, as well as inability to reverse the present rising rates of obesity, will lead to economically-unsustainable costs of health care in the next 10–20 years. Preventative strategies for metabolic syndrome are required to slow rates of progression and to reduce dependence on costly medical management. A notable development is recent evidence that shows that diet and exercise are more effective than drug treatment in preventing the development of type-2 diabetes in high-risk individuals. The LIPGENE project will investigate dietary fat quality as a strategy for the prevention of metabolic syndrome and identify food chain approaches that can support consumer attempts to alter their dietary patterns.

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