Plasticizers and Cardiovascular Health: Role of Adipose Tissue Dysfunction

Since the 1950s, the production of plastics has increased 200-fold, reaching 360 million tonnes in 2019. Plasticizers, additives that modify the flexibility and rigidity of the product, are ingested as they migrate into food and beverages. Human exposure is continuous and widespread; between 75 and 97% of urine samples contain detectable levels of bisphenols and phthalates, the most common plasticizers. Concern over the toxicity of plasticizers arose in the late 1990s, largely focused around adverse developmental and reproductive effects. More recently, many studies have demonstrated that exposure to plasticizers increases the risk for obesity, type 2 diabetes, and cardiovascular disease (CVD). In the 2000s, many governments including Canada, the United States and European countries restricted the use of certain plasticizers in products targeted towards infants and children. Resultant consumer pressure motivated manufacturers to substitute plasticizers with analogues, which have been marketed as safe. However, data on the effects of these new substitutes are limited and data available to-date suggest that many exhibit similar properties to the chemicals they replaced. The adverse effects of plasticizers have largely been attributed to their endocrine disrupting properties, which modulate hormone signaling. Adipose tissue has been well-documented to be a target of the disrupting effects of both bisphenols and phthalates. Since adipose tissue function is a key determinant of cardiovascular health, adverse effects of plasticizers on adipocyte signaling and function may underlie their link to cardiovascular disease. Herein, we discuss the current evidence linking bisphenols and phthalates to obesity and CVD and consider how documented impacts of these plasticizers on adipocyte function may contribute to the development of CVD.

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Long non-coding RNAs in regulation of adipogenesis and adipose tissue function

eLife ◽

10.7554/elife.59053 ◽

2020 ◽

Vol 9 ◽

Author(s):

Tiziana Squillaro ◽

Gianfranco Peluso ◽

Umberto Galderisi ◽

Giovanni Di Bernardo

Keyword(s):

Gene Expression ◽

Adipose Tissue ◽

Drug Targets ◽

Metabolic Diseases ◽

Tissue Development ◽

Cellular Functions ◽

Adipose Tissue Development ◽

And Function

Complex interaction between genetics, epigenetics, environment, and nutrition affect the physiological activities of adipose tissues and their dysfunctions, which lead to several metabolic diseases including obesity or type 2 diabetes. Here, adipogenesis appears to be a process characterized by an intricate network that involves many transcription factors and long noncoding RNAs (lncRNAs) that regulate gene expression. LncRNAs are being investigated to determine their contribution to adipose tissue development and function. LncRNAs possess multiple cellular functions, and they regulate chromatin remodeling, along with transcriptional and post-transcriptional events; in this way, they affect gene expression. New investigations have demonstrated the pivotal role of these molecules in modulating white and brown/beige adipogenic tissue development and activity. This review aims to provide an update on the role of lncRNAs in adipogenesis and adipose tissue function to promote identification of new drug targets for treating obesity and related metabolic diseases.

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The Role of Adiponectin in Cancer: A Review of Current Evidence

Endocrine Reviews ◽

10.1210/er.2011-1015 ◽

2012 ◽

Vol 33 (4) ◽

pp. 547-594 ◽

Cited By ~ 340

Author(s):

Maria Dalamaga ◽

Kalliope N. Diakopoulos ◽

Christos S. Mantzoros

Keyword(s):

Adipose Tissue ◽

Cancer Progression ◽

Anticancer Agents ◽

Current Evidence ◽

Excess Body Weight ◽

Increased Risk ◽

Patients With Diabetes

Excess body weight is associated not only with an increased risk of type 2 diabetes and cardiovascular disease (CVD) but also with various types of malignancies. Adiponectin, the most abundant protein secreted by adipose tissue, exhibits insulin-sensitizing, antiinflammatory, antiatherogenic, proapoptotic, and antiproliferative properties. Circulating adiponectin levels, which are determined predominantly by genetic factors, diet, physical activity, and abdominal adiposity, are decreased in patients with diabetes, CVD, and several obesity-associated cancers. Also, adiponectin levels are inversely associated with the risk of developing diabetes, CVD, and several malignancies later in life. Many cancer cell lines express adiponectin receptors, and adiponectin in vitro limits cell proliferation and induces apoptosis. Recent in vitro studies demonstrate the antiangiogenic and tumor growth-limiting properties of adiponectin. Studies in both animals and humans have investigated adiponectin and adiponectin receptor regulation and expression in several cancers. Current evidence supports a role of adiponectin as a novel risk factor and potential diagnostic and prognostic biomarker in cancer. In addition, either adiponectin per se or medications that increase adiponectin levels or up-regulate signaling pathways downstream of adiponectin may prove to be useful anticancer agents. This review presents the role of adiponectin in carcinogenesis and cancer progression and examines the pathophysiological mechanisms that underlie the association between adiponectin and malignancy in the context of a dysfunctional adipose tissue in obesity. Understanding of these mechanisms may be important for the development of preventive and therapeutic strategies against obesity-associated malignancies.

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Perivascular adipose tissue and coronary atherosclerosis

Heart ◽

10.1136/heartjnl-2017-312324 ◽

2018 ◽

Vol 104 (20) ◽

pp. 1654-1662 ◽

Cited By ~ 15

Author(s):

Jennifer Mancio ◽

Evangelos K Oikonomou ◽

Charalambos Antoniades

Keyword(s):

Cardiovascular Disease ◽

Adipose Tissue ◽

Cardiovascular Health ◽

Biological Significance ◽

Vascular Wall ◽

Clinical Diagnostics ◽

Current Evidence ◽

Perivascular Adipose Tissue ◽

Inflammatory Status ◽

Spatial Changes

Adipose tissue (AT) is no longer viewed as a passive, energy-storing depot, and a growing body of evidence supports the concept that both quantitative and qualitative aspects of AT are critical in determining an individual’s cardiometabolic risk profile. Among all AT sites, perivascular AT (PVAT) has emerged as a depot with a distinctive biological significance in cardiovascular disease given its close anatomical proximity to the vasculature. Recent studies have suggested the presence of complex, bidirectional paracrine and vasocrine signalling pathways between the vascular wall and its PVAT, with far-reaching implications in cardiovascular diagnostics and therapeutics. In this review, we first discuss the biological role of PVAT in both cardiovascular health and disease, highlighting its dual pro-atherogenic and anti-atherogenic roles, as well as potential therapeutic targets in cardiovascular disease. We then review current evidence and promising new modalities on the non-invasive imaging of epicardial AT and PVAT. Specifically, we present how our expanding knowledge on the bidirectional interplay between the vascular wall and its PVAT can be translated into novel clinical diagnostics tools to assess coronary inflammation. To this end, we present the example of a new CT-based method that tracks spatial changes in PVAT phenotype to extract information about the inflammatory status of the adjacent vasculature, highlighting the numerous diagnostic and therapeutic opportunities that arise from our increased understanding of PVAT biology.

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The Role of Brown Adipose Tissue in Cardiovascular Disease Protection: Current Evidence and Future Directions

International Journal of Clinical Research & Trials ◽

10.15344/2456-8007/2019/136 ◽

2019 ◽

Vol 4 (2) ◽

Author(s):

Renata Pereira ◽

Samy McFarlane

Keyword(s):

Cardiovascular Disease ◽

Adipose Tissue ◽

Brown Adipose Tissue ◽

Current Evidence ◽

Future Directions ◽

Brown Adipose

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Metabolic Inflammation and Insulin Resistance in Obesity

Circulation Research ◽

10.1161/circresaha.119.315896 ◽

2020 ◽

Vol 126 (11) ◽

pp. 1549-1564 ◽

Cited By ~ 15

Author(s):

Huaizhu Wu ◽

Christie M. Ballantyne

Keyword(s):

Diabetes Mellitus ◽

Insulin Resistance ◽

Type 2 Diabetes ◽

Cardiovascular Disease ◽

Type 2 Diabetes Mellitus ◽

Adipose Tissue ◽

The United States ◽

Atherosclerotic Cardiovascular Disease ◽

Metabolic Inflammation

Obesity is becoming an epidemic in the United States and worldwide and increases risk for many diseases, particularly insulin resistance, type 2 diabetes mellitus, and cardiovascular disease. The mechanisms linking obesity with these diseases remain incompletely understood. Over the past 2 to 3 decades, it has been recognized that in obesity, inflammation, with increased accumulation and inflammatory polarization of immune cells, takes place in various tissues, including adipose tissue, skeletal muscle, liver, gut, pancreatic islet, and brain and may contribute to obesity-linked metabolic dysfunctions, leading to insulin resistance and type 2 diabetes mellitus. Therapies targeting inflammation have shed light on certain obesity-linked diseases, including type 2 diabetes mellitus and atherosclerotic cardiovascular disease, but remain to be tested further and confirmed in clinical trials. This review focuses on inflammation in adipose tissue and its potential role in insulin resistance associated with obesity.

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Abstract # P-18: Economic Burden of Type 2 Diabetes Mellitus in Patients with Cardiovascular Disease in Commercially-Insured Patients in the United States

Endocrine Practice ◽

10.1016/s1530-891x(20)43831-5 ◽

2016 ◽

Vol 22 ◽

pp. 21-22

Author(s):

Weijia Wang ◽

Eileen M. Farrelly ◽

Sharash Shetty ◽

Dana Stafkey-Mailey ◽

Stephen D. Sander ◽

...

Keyword(s):

Diabetes Mellitus ◽

United States ◽

Type 2 Diabetes ◽

Cardiovascular Disease ◽

Type 2 Diabetes Mellitus ◽

Economic Burden ◽

The United States ◽

Insured Patients

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An Overview of Adipose Tissue ACE2 Modulation by Diet and Obesity. Potential Implications in COVID-19 Infection and Severity

International Journal of Molecular Sciences ◽

10.3390/ijms22157975 ◽

2021 ◽

Vol 22 (15) ◽

pp. 7975

Author(s):

Saioa Gómez-Zorita ◽

Iñaki Milton-Laskibar ◽

Laura García-Arellano ◽

Marcela González ◽

María P. Portillo

Keyword(s):

Adipose Tissue ◽

Protective Role ◽

Inflammatory Factors ◽

Current Evidence ◽

Disease Outcomes ◽

Lower Activation ◽

Two Factors ◽

Obese Subjects ◽

Ace2 Gene

The present review is aimed at analysing the current evidence concerning the potential modulation of obesity and/or diet in adipose tissue ACE2. Additionally, the potential implications of these effects on COVID-19 are also addressed. The results published show that diet and obesity are two factors that effectively influence the expression of Ace2 gene in adipose tissue. However, the shifts in this gene do not always occur in the same direction, nor with the same intensity. Additionally, there is no consensus regarding the implications of increased adipose tissue ACE2 expression in health. Thus, while in some studies a protective role is attributed to ACE2 overexpression, other studies suggest otherwise. Similarly, there is much debate regarding the role played by ACE2 in COVID-19 in terms of degree of infection and disease outcomes. The greater risk of infection that may hypothetically derive from enhanced ACE2 expression is not clear since the functionality of the enzyme seems to be as important as the abundance. Thus, the greater abundance of ACE2 in adipose tissue of obese subjects may be counterbalanced by its lower activation. In addition, a protective role of ACE2 overexpression has also been suggested, associated with the increase in anti-inflammatory factors that it may produce.

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Vitamin D signalling in adipose tissue

British Journal Of Nutrition ◽

10.1017/s0007114512003285 ◽

2012 ◽

Vol 108 (11) ◽

pp. 1915-1923 ◽

Cited By ~ 161

Author(s):

Cherlyn Ding ◽

Dan Gao ◽

John Wilding ◽

Paul Trayhurn ◽

Chen Bing

Keyword(s):

Vitamin D ◽

Adipose Tissue ◽

Vitamin D Deficiency ◽

Vitamin D Metabolites ◽

Hydroxyvitamin D ◽

The Metabolic Syndrome ◽

Prevalence Of Obesity ◽

Adipose Tissue Development ◽

And Function

Vitamin D deficiency and the rapid increase in the prevalence of obesity are both considered important public health issues. The classical role of vitamin D is in Ca homoeostasis and bone metabolism. Growing evidence suggests that the vitamin D system has a range of physiological functions, with vitamin D deficiency contributing to the pathogenesis of several major diseases, including obesity and the metabolic syndrome. Clinical studies have shown that obese individuals tend to have a low vitamin D status, which may link to the dysregulation of white adipose tissue. Recent studies suggest that adipose tissue may be a direct target of vitamin D. The expression of both the vitamin D receptor and 25-hydroxyvitamin D 1α-hydroxylase (CYP27B1) genes has been shown in murine and human adipocytes. There is evidence that vitamin D affects body fat mass by inhibiting adipogenic transcription factors and lipid accumulation during adipocyte differentiation. Some recent studies demonstrate that vitamin D metabolites also influence adipokine production and the inflammatory response in adipose tissue. Therefore, vitamin D deficiency may compromise the normal metabolic functioning of adipose tissue. Given the importance of the tissue in energy balance, lipid metabolism and inflammation in obesity, understanding the mechanisms of vitamin D action in adipocytes may have a significant impact on the maintenance of metabolic health. In the present review, we focus on the signalling role of vitamin D in adipocytes, particularly the potential mechanisms through which vitamin D may influence adipose tissue development and function.

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Adipose tissue inflammation and metabolic dysfunction: a clinical perspective

Hormone Molecular Biology and Clinical Investigation ◽

10.1515/hmbci-2013-0032 ◽

2013 ◽

Vol 15 (1) ◽

Cited By ~ 2

Author(s):

Charmaine S. Tam ◽

Leanne M. Redman

Keyword(s):

Insulin Resistance ◽

Adipose Tissue ◽

Low Grade ◽

Metabolic Dysfunction ◽

Adipose Tissue Inflammation ◽

Tissue Inflammation ◽

Proinflammatory Mediators ◽

Low Grade Inflammation

AbstractObesity is characterized by a state of chronic low-grade inflammation due to increased immune cells, specifically infiltrated macrophages into adipose tissue, which in turn secrete a range of proinflammatory mediators. This nonselective low-grade inflammation of adipose tissue is systemic in nature and can impair insulin signaling pathways, thus, increasing the risk of developing insulin resistance and type 2 diabetes. The aim of this review is to provide an update on clinical studies examining the role of adipose tissue in the development of obesity-associated complications in humans. We will discuss adipose tissue inflammation during different scenarios of energy imbalance and metabolic dysfunction including obesity and overfeeding, weight loss by calorie restriction or bariatric surgery, and conditions of insulin resistance (diabetes, polycystic ovarian syndrome).

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