Dataset Information

Loss of anti-contractile effect of perivascular adipose tissue in offspring of obese rats.

ABSTRACT:

Rationale

Maternal 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.

Objective

The objective of this study was to determine whether maternal obesity pre-programmes offspring to develop PVAT dysfunction in later life.

Methods

Female 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.

Results

Only 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??M 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??M 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.

Conclusions

The 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.

SUBMITTER: Zaborska KE

PROVIDER: S-EPMC4973217 | biostudies-literature | 2016 Aug

REPOSITORIES: biostudies-literature

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Publications

Loss of anti-contractile effect of perivascular adipose tissue in offspring of obese rats.

Zaborska K E KE Wareing M M Edwards G G Austin C C

International journal of obesity (2005) 20160422 8

<h4>Rationale</h4>Maternal 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.<h4>Objective</h4>The objective of this study was to determine whether maternal obesity pre-programmes offspring to develop PVAT dysfunction in later life.<h4>Methods</h4>Female Sprague-Dawley rats were fed a diet containing 10% (control) or 45% fa ...[more]

PMID: 27102050

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Project description:Background and purposeObesity is associated with structural and functional changes in perivascular adipose tissue (PVAT), favouring release of reactive oxygen species (ROS), vasoconstrictor and proinflammatory factors. The cytokine TNF-? induces vascular dysfunction and is produced by PVAT. We tested the hypothesis that obesity-associated PVAT dysfunction was mediated by augmented mitochondrial ROS (mROS) generation due to increased TNF-? production in this tissue.Experimental approachC57Bl/6J and TNF-? receptor-deficient mice received control or high fat diet (HFD) for 18 weeks. We used pharmacological tools to determine the participation of mROS in PVAT dysfunction. Superoxide anion (O2.- ) and H2 O2 were assayed in PVAT and aortic rings were used to assess vascular function.Key resultsAortae from HFD-fed obese mice displayed increased contractions to phenylephrine and loss of PVAT anti-contractile effect. Inactivation of O2.- , dismutation of mitochondria-derived H2 O2 , uncoupling of oxidative phosphorylation and Rho kinase inhibition, decreased phenylephrine-induced contractions in aortae with PVAT from HFD-fed mice. O2.- and H2 O2 were increased in PVAT from HFD-fed mice. Mitochondrial respiration analysis revealed decreased O2 consumption rates in PVAT from HFD-fed mice. TNF-? inhibition reduced H2 O2 levels in PVAT from HFD-fed mice. PVAT dysfunction, i.e. increased contraction to phenylephrine in PVAT-intact aortae, was not observed in HFD-obese mice lacking TNF-? receptors. Generation of H2 O2 was prevented in PVAT from TNF-? receptor deficient obese mice.Conclusion and implicationsTNF-?-induced mitochondrial oxidative stress is a key and novel mechanism involved in obesity-associated PVAT dysfunction. These findings elucidate molecular mechanisms whereby oxidative stress in PVAT could affect vascular function.Linked articlesThis article is part of a themed section on Molecular Mechanisms Regulating Perivascular Adipose Tissue - Potential Pharmacological Targets? To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v174.20/issuetoc.

Dataset Information

Loss of anti-contractile effect of perivascular adipose tissue in offspring of obese rats.

Rationale

Objective

Methods

Results

Conclusions

Publications

Loss of anti-contractile effect of perivascular adipose tissue in offspring of obese rats.

Similar Datasets

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