The Sick Adipose Tissue: New Insights Into Defective Signaling and Crosstalk With the Myocardium

Adipose tissue (AT) biology is linked to cardiovascular health since obesity is associated with cardiovascular disease (CVD) and positively correlated with excessive visceral fat accumulation. AT signaling to myocardial cells through soluble factors known as adipokines, cardiokines, branched-chain amino acids and small molecules like microRNAs, undoubtedly influence myocardial cells and AT function via the endocrine-paracrine mechanisms of action. Unfortunately, abnormal total and visceral adiposity can alter this harmonious signaling network, resulting in tissue hypoxia and monocyte/macrophage adipose infiltration occurring alongside expanded intra-abdominal and epicardial fat depots seen in the human obese phenotype. These processes promote an abnormal adipocyte proteomic reprogramming, whereby these cells become a source of abnormal signals, affecting vascular and myocardial tissues, leading to meta-inflammation, atrial fibrillation, coronary artery disease, heart hypertrophy, heart failure and myocardial infarction. This review first discusses the pathophysiology and consequences of adipose tissue expansion, particularly their association with meta-inflammation and microbiota dysbiosis. We also explore the precise mechanisms involved in metabolic reprogramming in AT that represent plausible causative factors for CVD. Finally, we clarify how lifestyle changes could promote improvement in myocardiocyte function in the context of changes in AT proteomics and a better gut microbiome profile to develop effective, non-pharmacologic approaches to CVD.

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Expression of adipocytokine genes and their content in various adipose tissue sites in patients with heart diseases

10.21203/rs.3.rs-53273/v1 ◽

2020 ◽

Author(s):

Olga Gruzdeva ◽

Yulia Dyleva ◽

Ekaterina Belik ◽

Daria Borodkina ◽

Maxim Sinitsky ◽

...

Keyword(s):

Gene Expression ◽

Coronary Artery Disease ◽

Adipose Tissue ◽

Coronary Artery ◽

Mitral Valve ◽

Valve Replacement ◽

Mitral Valve Replacement ◽

Biologically Active ◽

Fat Depots ◽

Artery Disease

Abstract Background Adipose tissue (AT) is an endocrine and paracrine organ that synthesizes biologically active adipocytokines, which affect inflammation, fibrosis, and atherogenesis. Epicardial and perivascular fat depots are of great interest owing to potential effects on the myocardium and blood vessels. Objective To assess expression and secretion of adipocytokine genes in adipose tissue in patients coronary artery disease (CAD) and patients with aortic or mitral valve replacement. Methods The study included 84 patients with CAD and 50 patients with aortic or mitral valve replacement. Adipocytes were isolated from subcutaneous (SAT), epicardial (EAT), and perivascular AT (PVAT) samples. Isolated adipocytes were cultured for 24 h after which, gene expression and secretion levels of selected adipokines and cytokines in the culture medium were determined. Results The study parameters differed depending on the adipose tissue location. EAT adipocytes in CAD patients were characterized by a pronounced imbalance in the adipokine system. EAT had the lowest adiponectin gene expression and secretion, regardless of nosology and high expression levels of the leptin gene, its receptor, and interleukin-6 (IL-6) were detected. High leptin and IL-6 levels resulted in increased pro-inflammatory activity, as observed in both EAT and PVAT adipocytes, especially in individuals with coronary artery disease. Conclusion The "protective" potential of adipose tissue depends on its location.

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Associations of adipocytokine expression and cardiovascular risk factors in stable coronary artery disease

Russian Journal of Cardiology ◽

10.15829/1560-4071-2021-4318 ◽

2021 ◽

Vol 26 (3) ◽

pp. 4318

Author(s):

E. V. Belik ◽

O. V. Gruzdeva ◽

Yu. A. Dyleva ◽

D. A. Borodkina ◽

M. Yu. Sinitsky ◽

...

Keyword(s):

Risk Factors ◽

Coronary Artery Disease ◽

Adipose Tissue ◽

Cardiovascular Risk ◽

Coronary Artery ◽

Cardiovascular Risk Factors ◽

Stable Coronary Artery Disease ◽

Perivascular Adipose Tissue ◽

Fat Depots ◽

Artery Disease

Aim. To determine the expression of adiponectin, leptin and I interleukin-6 (IL-6) in subcutaneous, epicardial and perivascular adipose tissue, depending on the presence of cardiovascular risk factors.Material and methods. The study included 90 patients with stable coronary artery disease (CAD) who underwent coronary artery bypass grafting. Samples of adipose tissue were obtained during surgery. The levels of matrix ribonucleic acid (mRNA) of the studied adipocytokines were determined in the presence/absence of the main cardiovascular risk factors.Results. Differences in the expression of genes of the studied adipocytokines in different sex and age groups of patients were revealed, depending on the tissue belonging of adipocytes. Expression of adiponectin in the epicardial and perivascular adipose tissue (EАT and PVAT, respectively), as well as of leptin in the PVAT was less pronounced in men. However, the level of IL-6 mRNA in the subcutaneous adipose tissue (SAT) of men was three times higher than in women, and in the PVAT it was lower. The maximum expression of leptin and IL-6 in the EAT and PVAT was found in persons aged 50-59 years. The presence of dyslipidemia is associated with a decrease in the expression of adiponectin in the EAT, PVAT, and IL-6 in the PVAT. In patients with hypertension (HTN), there was a low level of adiponectin mRNA in the EAT against the background of high leptin levels in the EAT and IL-6 in SAT and EAT. In hypertension with a duration of more than 20 years, there was a decrease in adiponectin expression and an increase in leptin in all types of AT. In smokers, an increase in the expression of adiponectin in the SAT, EAT, PVAT and leptin in the SAT, EAT was found.Conclusion. Associations of traditional cardiovascular risk factors with imbalance of adipocytokines of local fat depots in patients with CAD were revealed. The detected imbalance is manifested by a decrease in the expression of cardioprotective adiponectin in the EAT, PVAT, an increase in leptin and IL-6, which is an unfavorable sign. The presence of such risk factors as male sex, age of 50-59 years, dyslipidemia and hypertension in patients can enhance atherogenesis and contribute to the further progression of CAD.

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Regulation of p27 and Cdk2 Expression in Different Adipose Tissue Depots in Aging and Obesity

International Journal of Molecular Sciences ◽

10.3390/ijms222111745 ◽

2021 ◽

Vol 22 (21) ◽

pp. 11745

Author(s):

Ignacio Colón-Mesa ◽

Marta Fernández-Galilea ◽

Neira Sáinz ◽

Marta Lopez-Yus ◽

Jose M. Artigas ◽

...

Keyword(s):

Type 2 Diabetes ◽

Adipose Tissue ◽

Subcutaneous White Adipose Tissue ◽

Visceral Fat Accumulation ◽

Fat Depots ◽

Adipose Tissue Depots ◽

Obesity In Mice ◽

Cdk2 Expression ◽

Lower Expression

Aging usually comes associated with increased visceral fat accumulation, reaching even an obesity state, and favoring its associated comorbidities. One of the processes involved in aging is cellular senescence, which is highly dependent on the activity of the regulators of the cell cycle. The aim of this study was to analyze the changes in the expression of p27 and cdk2 in different adipose tissue depots during aging, as well as their regulation by obesity in mice. Changes in the expression of p27 and CDK2 in visceral and subcutaneous white adipose tissue (WAT) biopsies were also analyzed in a human cohort of obesity and type 2 diabetes. p27, but not cdk2, exhibits a lower expression in subcutaneous than in visceral WAT in mice and humans. p27 is drastically downregulated by aging in subcutaneous WAT (scWAT), but not in gonadal WAT, of female mice. Obesity upregulates p27 and cdk2 expression in scWAT, but not in other fat depots of aged mice. In humans, a significant upregulation of p27 was observed in visceral WAT of subjects with obesity. Taken together, these results show a differential adipose depot-dependent regulation of p27 and cdk2 in aging and obesity, suggesting that p27 and cdk2 could contribute to the adipose-tissue depot’s metabolic differences. Further studies are necessary to fully corroborate this hypothesis.

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QUANTIFICATION OF ECTOPIC FAT DEPOTS IN PATIENTS WITH CORONARY HEART DISEASE

Research n Practical Medicine Journal ◽

10.17709/2409-2231-2019-6-3-4 ◽

2019 ◽

Vol 6 (3) ◽

pp. 40-50

Author(s):

A. N. Kokov ◽

N. K. Brel ◽

V. L. Masenko ◽

O. V. Gruzdeva ◽

Yu. A. Dyleva ◽

...

Keyword(s):

Coronary Artery Disease ◽

Adipose Tissue ◽

Heart Disease ◽

Ectopic Fat ◽

Fat Depots ◽

Prevalence Of Obesity ◽

Artery Disease ◽

Visceral Adipose ◽

Quantitative Indicators ◽

Area And Volume

Purpose of the study. A comprehensive quantification of ectopic fat depots using modern methods of radiation diagnosis in patients with ischemic heart disease. Patients and methods. The study included 76 patients with a verified diagnosis of ischemic heart disease (IHD). The control group consisted of 32 people without clinical manifestations of IHD. All patients to assess the area and volume of visceral adipose tissue, as well as measuring the volume of paraaortic adipose tissue at the level of the abdominal aorta were performed multispiral computed tomography (MSCT) at the level of L3–L5 vertebrae. In order to visualize and morphometry pericoronary and paraaortic adipose tissue at the level of the thoracic aorta, patients in both groups were performed MSCT angiography of the coronary arteries with ECG synchronization. To visualize the epicardial fat depot with an assessment of the thickness of the adipose tissue layer, magnetic resonance imaging (MRI) of the heart was performed. Results. During the comparative analysis, significantly higher values of quantitative indicators of the main ectopic fat depots were noted in patients with coronary artery disease. Estimation of the prevalence of obesity according to BMI data in the compared groups showed no significant differences. Considering the standard values of the area and volume of visceral adipose tissue, the prevalence of obesity was significantly higher in the group of patients with IHD. Conducted correlation analysis showed the relationship of quantitative indicators of ectopic visceral, para-aortic and epicardial fat depots. Moreover, in the group of patients with IHD, stronger correlations were found between the fat depots of different localization (r = 0,71, p = 0,013 in group with IHD and r = 0,59, p = 0,039 in group without IND). Conclusion. Modern tomographic methods allow for a comprehensive quantification of ectopic fat depots. Significantly higher morphometry indices of the studied fat depots in patients with coronary artery disease demonstrate the need to develop a unified diagnostic algorithm for reliable stratification of cardiometabolic risk.

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Expression of adipocytokine in heart fat depots depending on the degree of coronary artery atherosclerosis in patients with coronary artery disease

Annals of the Russian academy of medical sciences ◽

10.15690/vramn1388 ◽

2021 ◽

Vol 76 (2) ◽

pp. 159-168 ◽

Cited By ~ 1

Author(s):

Olga V. Gruzdeva ◽

Yulia A. Dyleva ◽

Ekaterina V. Belik ◽

Olga E. Akbasheva ◽

Daria A. Borodkinа ◽

...

Keyword(s):

Coronary Artery Disease ◽

Coronary Heart Disease ◽

Adipose Tissue ◽

Heart Disease ◽

Coronary Artery ◽

Atherosclerotic Lesion ◽

Moderate Degree ◽

Perivascular Adipose Tissue ◽

Fat Depots ◽

Artery Disease

Background. In coronary artery disease, a change in the adipocytokine content of local fat depots of the heart is observed. However, it has not yet been established whether the expression levels of the studied parameters are really related to the degree of atherosclerotic lesion of the spacecraft. Aims to identify the features of the expression of adiponectin, leptin and IL-6 by adipocytes of epicardial, perivascular and subcutaneous adipose tissue depending on the degree of atherosclerotic lesion of the coronary channel in coronary heart disease. Materials and methods. The study conducted at the Research Institute for Complex Issues of Cardiovascular Disease in 20172020, included 84 patients with coronary heart disease (CAD), of which 39 with a moderate degree of atherosclerotic lesion of the coronary artery (CA) ( 22 points on the SYNTAX Score scale), 20 with severe (2331 points) and 25 with extremely severe ( 32 points). Biopsies of subcutaneous (SAT), epicardial (EAT) and perivascular adipose tissue (PVAT) were obtained during elective coronary artery bypass grafting (CABG). The expression of adipocytokine genes was determined using polymerase chain reaction (real-time PCR) using TaqMan probes and the concentration of the studied adipocytokines in adipocyte culture medium by enzyme immunoassay. Statistical analysis was performed using Statistica 9.0, a one-dimensional and multi-dimensional logistic regression analysis. Results. In CAD in adipocytes of the cardiac fat depot, a shift in the balance of adipocytokines is observed towards increased expression and secretion of leptin, IL-6 and a decrease in adiponectin with maximum manifestation in severe and extremely severe coronary lesions. Adipocytes of EAT were characterized by the minimal expression of the adiponectin gene against the background of the maximum leptin and IL-6 in comparison with adipocytes SAT and PVAT. Conclusions. Low expression of the adiponectin in EAT and PVAT against the background of increased expression of leptin and IL-6 is associated with an increase in the degree of atherosclerotic lesion of the coronary channel.

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