Mechanistic Links Between Obesity, Diabetes, and Blood Pressure: Role of Perivascular Adipose Tissue

Saxton, Sophie; Clark, Ben; Withers, Sarah; Eringa, Etto C.; Heagerty, Anthony M.

doi:10.1152/physrev.00034.2018

Cited by 188 publications

(146 citation statements)

References 784 publications

(1,012 reference statements)

Supporting

Mentioning

122

Contrasting

Unclassified

Order By: Relevance

“…Obesity has reached epidemic proportions worldwide owing to the paradigm shift to a high-calorie diet and a sedentary lifestyle. Moreover, obesity has placed a heavy financial burden on healthcare costs related to numerous pathologies, especially CVD, including coronary artery disease, arrhythmias, heart failure, and sudden cardiac death [29,30]. In the current study, we investigated the global molecular events implicated in the mechanism of cardiac structural remodeling using RNA-Sequencing analysis in an HFD-induced obesity mouse model.…”

Section: Discussionmentioning

confidence: 99%

Cardiac Transcriptome Analysis Reveals Nr4a1 Mediated Glucose Metabolism Dysregulation in Response to High-Fat Diet

Men

Hui

Guan

et al. 2020

Genes

View full text Add to dashboard Cite

Obesity is associated with an increased risk of developing cardiovascular disease (CVD), with limited alterations in cardiac genomic characteristics known. Cardiac transcriptome analysis was conducted to profile gene signatures in high-fat diet (HFD)-induced obese mice. A total of 184 differentially expressed genes (DEGs) were identified between groups. Based on the gene ontology (GO) term enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis of DEGs, the critical role of closely interlocked glucose metabolism was determined in HFD-induced cardiac remodeling DEGs, including Nr4a1, Fgf21, Slc2a3, Pck1, Gck, Hmgcs2, and Bpgm. Subsequently, the expression levels of these DEGs were evaluated in both the myocardium and palmitic acid (PA)-stimulated H9c2 cardiomyocytes using qPCR. Nr4a1 was highlighted according to its overexpression resulting from the HFD. Additionally, inhibition of Nr4a1 by siRNA reversed the PA-induced altered expression of glucose metabolism-related DEGs and hexokinase 2 (HK2), the rate-limiting enzyme in glycolysis, thus indicating that Nr4a1 could modulate glucose metabolism homeostasis by regulating the expression of key enzymes in glycolysis, which may subsequently influence cardiac function in obesity. Overall, we provide a comprehensive understanding of the myocardium transcript molecular framework influenced by HFD and propose Nr4a1 as a key glucose metabolism target in obesity-induced CVD.

show abstract

Section: Discussionmentioning

confidence: 99%

Cardiac Transcriptome Analysis Reveals Nr4a1 Mediated Glucose Metabolism Dysregulation in Response to High-Fat Diet

Men

Hui

Guan

et al. 2020

Genes

View full text Add to dashboard Cite

show abstract

“…However, adipose tissue depots are diverse in function and type. Adipose tissue has striking heterogeneity, with changes in phenotype relating to its location and physiological function (reviewed [18]). There are two classical types of adipose tissue; brown and white adipose tissue.…”

Section: Adipose Tissuementioning

confidence: 99%

MiRNAs as Novel Adipokines: Obesity-Related Circulating MiRNAs Influence Chemosensitivity in Cancer Patients

Withers

Dewhurst

Hammond

et al. 2020

ncRNA

Self Cite

View full text Add to dashboard Cite

Adipose tissue is an endocrine organ, capable of regulating distant physiological processes in other tissues via the release of adipokines into the bloodstream. Recently, circulating adipose-derived microRNAs (miRNAs) have been proposed as a novel class of adipokine, due to their capacity to regulate gene expression in tissues other than fat. Circulating levels of adipokines are known to be altered in obese individuals compared with typical weight individuals and are linked to poorer health outcomes. For example, obese individuals are known to be more prone to the development of some cancers, and less likely to achieve event-free survival following chemotherapy. The purpose of this review was twofold; first to identify circulating miRNAs which are reproducibly altered in obesity, and secondly to identify mechanisms by which these obesity-linked miRNAs might influence the sensitivity of tumors to treatment. We identified 8 candidate circulating miRNAs with altered levels in obese individuals (6 increased, 2 decreased). A second literature review was then performed to investigate if these candidates might have a role in mediating resistance to cancer treatment. All of the circulating miRNAs identified were capable of mediating responses to cancer treatment at the cellular level, and so this review provides novel insights which can be used by future studies which aim to improve obese patient outcomes.

show abstract

“…Adipose tissue is classically defined as white or brown adipose tissue, with the colour reflecting the number of mitochondria within the cell, and further non‐classical categories of beige and pink, representing tissue that has undergone a phenotypic change from white to brown or that has transformed into lobulo‐alveolar glandular structures that produce milk, respectively. This has been reviewed recently by Saxton, Clark, Withers, Eringa, & Heagerty (2019). What is common to these different depots is twofold.…”

Section: Perivascular Adipose Tissuementioning

confidence: 99%

Perivascular adipose tissue: An immune cell metropolis

Saxton

Heagerty

Withers

2020

Experimental Physiology

View full text Add to dashboard Cite

New Findings What is the topic of this review?The review discusses how eosinophils can contribute to the function of perivascular adipose tissue and explores the mechanisms involved. What advances does it highlight?Understanding the communication between the cell populations that constitute perivascular adipose tissue function is important for exploring therapeutic options in the treatment of obesity‐related cardiovascular complications. This article highlights that eosinophils are able to contribute directly to healthy perivascular adipose tissue function. These immune cells contribute to adrenergic signalling and nitric oxide‐ and adiponectin‐dependent mechanisms in perivascular adipose tissue. Abstract Perivascular adipose tissue is a heterogeneous tissue that surrounds most blood vessels in the body. This review focuses on the contribution of eosinophils located within the adipose tissue to vascular contractility. A high‐fat diet reduces the number of these immune cells within perivascular adipose tissue, and this loss is linked to an increase in vascular contractility and hypertension. We explored the mechanisms by which eosinophils contribute to this function using genetically modified mice, ex vivo assessment of contractility and pharmacological tools. We found that eosinophils contribute to adrenergic signalling and nitric oxide‐ and adiponectin‐dependent mechanisms in perivascular adipose tissue. It is now important to explore whether manipulation of these pathways in obesity can alleviate cardiovascular complications, in order to determine whether eosinophils are a valid target for obesity‐related disease.

show abstract

Mechanistic Links Between Obesity, Diabetes, and Blood Pressure: Role of Perivascular Adipose Tissue

Cited by 188 publications

References 784 publications

Cardiac Transcriptome Analysis Reveals Nr4a1 Mediated Glucose Metabolism Dysregulation in Response to High-Fat Diet

Cardiac Transcriptome Analysis Reveals Nr4a1 Mediated Glucose Metabolism Dysregulation in Response to High-Fat Diet

MiRNAs as Novel Adipokines: Obesity-Related Circulating MiRNAs Influence Chemosensitivity in Cancer Patients

Perivascular adipose tissue: An immune cell metropolis

Contact Info

Product

Resources

About