High Fat Diet Attenuates the Anticontractile Activity of Aortic PVAT via a Mechanism Involving AMPK and Reduced Adiponectin Secretion

Almabrouk, Tarek Ali Mohamed; White, Anna; Ugusman, Azizah; Skiba, Dominik; Katwan, Omar J.; Alganga, Husam; Guzik, Tomasz J.; Touyz, Rhian M.; Salt, Ian P.; Kennedy, Simon

doi:10.3389/fphys.2018.00051

Cited by 54 publications

(57 citation statements)

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“…The current results indicated that HF diet fed rats exhibited decreased levels of circulating adiponectin and downregulation of its gene expression. Oppositely, hyperleptinemia was detected with upregulation of its gene expression in agreement with some data presented previously (Arita et al, 1999; Trayhurn and Beattie, 2001; Almabrouk et al, 2018). Interestingly, adiponectin level is inversely but leptin is directly correlated to obesity and insulin resistance (Koleva et al, 2013).…”

Section: Discussionsupporting

confidence: 92%

Pharmacological Action of a Pregnane Glycoside, Russelioside B, in Dietary Obese Rats: Impact on Weight Gain and Energy Expenditure

et al. 2018

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Background and purpose: Russelioside B (RB) is a pregnane glycoside obtained from Caralluma quadrangula; a herb with antidiabetic, anti-inflammatory, and antihyperlipidemic activities. The present experiment tested the possible role of RB in controlling weight gain in rats fed on high fat (HF) diet.Methods: RB was separated from the n-butanol fraction of the crude methanolic extract by chromatographic separation on a Si gel column according to the procedures described previously. The experiment of the biological assessment of RB used 32 male Wistar rats (4 groups, n = 8). Group 1 rats were fed with a palatable normal diet. Group 2, 3, and 4 were fed on HF diet for 16 weeks. Group 2 served as the HF diet control group while Group 3 and 4 received daily oral doses of RB (25 and 50 mg/kg) during the last four weeks. Animals’ parameters like weight gain, fasting level of blood sugar, serum lipids, and serum liver enzyme activities were measured. Liver or adipose tissue weight was divided by the rat’s body weight and multiplied by 100 to obtain the liver or adipose tissue index, respectively. Adipose tissues were processed for histopathological examination, measurement of mRNA expression of visfatin, leptin, adiponectin, uncoupling protein-1 (UCP-1), and carnitine palmitoyl transferase-1 (CPT-1). Furthermore, serum levels of insulin, interleukin-6 (IL-6), IL-1β, tumor necrosis factor-α (TNF-α), leptin, resistin, and adiponectin were assessed using ELISA kits.Results: Rats fed with the HF diet exhibited significant body weight gain, abnormal liver function, disturbed lipid profile, and greater serum level of pro-inflammatory cytokines in addition to greater insulin resistance, adipose tissue and liver indices. Further, rats fed with the HF diet displayed upregulations in the expression of visfatin and leptin with downregulations in the expression of adiponectin, UCP-1, and CPT-1 compared to normal rats. Interestingly, RB (25 or 50 mg/kg) favorably modulated the measured parameters.Conclusion: Data from this study documented the beneficial role of RB in diminishing weight gain, improving the inflammatory perturbations and energy expenditure in HF diet fed rats. Therefore, RB might be a promising candidate for obesity.

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Section: Discussionsupporting

confidence: 92%

Pharmacological Action of a Pregnane Glycoside, Russelioside B, in Dietary Obese Rats: Impact on Weight Gain and Energy Expenditure

et al. 2018

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“…It has been proposed that adiponectin induces anti-contractile effects through several mechanisms, including hyperpolarization of vascular smooth muscle cells, stimulating NO release and enhancing endothelial NO production (Xia & Li, 2017). Moreover, adiponectin reduces vascular oxidative stress by inhibiting NADPH oxidase (Antonopoulos et al 2015). We show that the anti-contractile activity of PVAT was absent in adult male offspring of mothers exposed to GIH, which is in keeping with other studies of a loss of anti-contractile activity in PVAT-intact mesenteric arteries from 12-and 24-week-old male rat offspring of dams a fed a high-fat diet (Zaborska et al 2016).…”

Section: Figure 10 Metabolic and Vascular Effects Of Gestational Intmentioning

confidence: 99%

“…Inflammation diminishes the anti‐contractility effects of PVAT (Nosalski & Guzik, ) and also reduces adiponectin secretion (Almabrouk et al . ) in mice. However, the effects of GIH on endothelial and PVAT function in offspring from GIH are unknown.…”

Section: Introductionmentioning

confidence: 97%

“…Perivascular adipose tissue (PVAT) modulates vascular reactivity through the secretion of bioactive molecules such as adiponectin (Xia & Li, 2017). Inflammation diminishes the anti-contractility effects of PVAT and also reduces adiponectin secretion (Almabrouk et al 2018) in mice. However, the effects of GIH on endothelial and PVAT function in offspring from GIH are unknown.…”

Section: Introductionmentioning

confidence: 99%

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Gestational intermittent hypoxia induces endothelial dysfunction, reduces perivascular adiponectin and causes epigenetic changes in adult male offspring

Badran

Yassin

Lin

et al. 2019

The Journal of Physiology

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Key points Obstructive sleep apnoea (OSA) is characterized by intermittent hypoxia, which causes oxidative stress and inflammation and increases the risk of cardiovascular disease. OSA during pregnancy causes adverse maternal and fetal outcomes. The effects of pre‐existing OSA in pregnant women on cardiometabolic outcomes in the offspring are unknown. We evaluated basic metabolic parameters, as well as aortic vascular and perivascular adipose tissue (PVAT) function in response to adiponectin, and examined DNA methylation of adiponectin gene promoter in PVAT in 16‐week‐old adult offspring exposed to gestational intermittent hypoxia (GIH). GIH decreased body weights at week 1 in both male and female offspring, and caused subsequent increases in body weight and food consumption in male offspring only. Adult female offspring had normal levels of lipids, glucose and insulin, with no endothelial dysfunction. Adult male offspring exhibited dyslipidaemia, insulin resistance and hyperleptinaemia. Decreased endothelial‐dependent vasodilatation, loss of anti‐contractile activity of PVAT and low circulating PVAT adiponectin levels, as well as increased pro‐inflammatory gene expression and DNA methylation of adiponectin gene promoter, occurred in adult male offspring. Our results suggest that male offspring of women with OSA could be at risk of developing cardiometabolic disease during adulthood. Abstract Perturbations during pregnancy can program the offspring to develop cardiometabolic diseases later in life. Obstructive sleep apnoea (OSA) is a chronic condition that frequently affects pregnancies and leads to adverse fetal outcomes. We assessed the offspring of female mice experiencing gestational intermittent hypoxia (GIH), a hallmark of OSA, for changes in metabolic profiles, aortic nitric oxide (NO)‐dependent relaxations, perivascular adipose tissue (PVAT) anti‐contractile activities and the responses to adiponectin, and DNA methylation of the adiponectin gene promoter in PVAT tissue. Pregnant mouse dams were exposed to intermittent hypoxic cycles (FnormalIO2 21–12%) for 18 days. GIH resulted in lower body weights of pups at week 1, followed by significant weight gain by week 16 of age in male but not female offspring. Plasma lipids, leptin and insulin resistance were higher in GIH male adult offspring. Endothelium‐dependent relaxation in response to ACh and the anti‐contractile activity of PVAT in the abdominal aorta was reduced in GIH adult male offspring. Incubation of arteries from GIH adult male offspring with adiponectin restored the anti‐contractile activity of PVAT. Both circulating and PVAT tissue homogenate levels of adiponectin, as well as gene expression of adiponectin in PVAT, were lower in GIH male offspring, along with an increased gene expression of inflammatory cytokines. Pyrosequencing of adiponectin gene promoter in PVAT showed increased DNA methylation in GIH male offspring. Our results indicate that GIH leads to vascular disease in adult male offspring through PVAT dysfunction, which was associate...

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“…Increased production of reactive oxygen species, which inactivates endothelial-derived nitric oxide (NO) 16,17 , may explain reduced agonist-induced vasodilation in obese animals. Impaired endothelium-dependent vasodilation in obesity may also arise from changes in potassium channel activity [18][19][20] , NO release 20 , or how perivascular adipose tissue modulates endothelial function [21][22][23] . The number of diverse signaling mechanisms proposed to account for endothelial dysfunction in obesity demonstrates how complex changes occur in this cell layer, and point to changes in another regulator that is common to each dysfunction.…”

Section: Introductionmentioning

confidence: 99%

Disrupted Endothelial Cell Heterogeneity and Network Organization Impairs Vascular Function in Prediabetic Obesity

Wilson

Zhang

Lee

et al. 2020

Preprint

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Rationale: Obesity is a major risk factor for diabetes and cardiovascular diseases such as hypertension, heart failure, and stroke. Impaired endothelial function occurs in the earliest stages of obesity and underlies vascular alterations giving rise to cardiovascular disease. However, the mechanisms that link weight gain to endothelial dysfunction are ill-defined. Increasing evidence suggests that, rather than being a population of uniformly responding cells, neighboring endothelial cells are highly heterogeneous and are organized as a communicating multicellular network that controls vascular function.Objective: To investigate the hypothesis that disrupted endothelial heterogeneity and network-level organization contributes to impaired vascular reactivity in obesity. Methods and Results:To study obesity-related vascular function without the complications associated with diabetes, we induced a state of prediabetic obesity in rats. Small artery diameter recordings confirmed nitric-oxide mediated vasodilator responses were dependent on increases in endothelial calcium levels and were impaired in obese animals. Single-photon imaging revealed a linear relationship between blood vessel relaxation and network-level calcium responses. Obesity did not alter the slope of this relationship, but impaired network-level endothelial calcium responses. The network itself was comprised of structural and functional components. The structural component, a hexagonal lattice network of endothelial cells, was unchanged in obesity. The functional network contained subpopulations of clustered agonist-sensing cells from which signals were communicate through the network. In obesity there were fewer but larger clusters of agonist-sensing cells and communication path lengths between clusters was increased. Communication between neighboring cells was unaltered in obesity. Altered network organization resulted in impaired, population-level calcium signaling and deficient endothelial control of vascular tone. Specialized subpopulations of endothelial cells had increased agonist sensitivity. These agonistresponsive cells were spatially clustered in a non-random manner and drove network level calcium responses. Communication between adjacent cells was unaltered in obesity, but there was a decrease in the size of the agonist-sensitive cell population and an increase in the clustering of agonist-responsive cells Conclusions: The distribution of cells in the endothelial network is critical in determining overall vascular function. Altered cell heterogeneity and arrangement in obesity decrease endothelial function and provide a novel framework for understanding compromised endothelial function in cardiovascular disease.

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High Fat Diet Attenuates the Anticontractile Activity of Aortic PVAT via a Mechanism Involving AMPK and Reduced Adiponectin Secretion

Cited by 54 publications

References 54 publications

Pharmacological Action of a Pregnane Glycoside, Russelioside B, in Dietary Obese Rats: Impact on Weight Gain and Energy Expenditure

Pharmacological Action of a Pregnane Glycoside, Russelioside B, in Dietary Obese Rats: Impact on Weight Gain and Energy Expenditure

Gestational intermittent hypoxia induces endothelial dysfunction, reduces perivascular adiponectin and causes epigenetic changes in adult male offspring

Disrupted Endothelial Cell Heterogeneity and Network Organization Impairs Vascular Function in Prediabetic Obesity

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