Pro-inflammatory profile of visceral adipose tissue and oxidative stress in severe obese patients carrying the variant rs4612666 C of NLRP3 gene

Obesity is an important preventable risk factor for morbidity and mortality from cardiometabolic disease. Oxidative stress (including in visceral adipose tissue) and chronic low-grade inflammation are the major underlying pathomechanisms. Monoamine oxidase (MAO) has recently emerged as an important source of cardiovascular oxidative stress. The present study was conducted to evaluate the role of MAO as contributor to reactive oxygen species (ROS) production in white adipose tissue and vessels harvested from patients undergoing elective abdominal surgery. To this aim, visceral adipose tissue and mesenteric artery branches were isolated from obese patients with chronic inflammation and used for organ bath, ROS production, quantitative real-time PCR, and immunohistology studies. The human visceral adipose tissue and mesenteric artery branches contain mainly the MAO-A isoform, as shown by the quantitative real-time PCR and immunohistology experiments. A significant upregulation of MAO-A, the impairment in vascular reactivity, and increase in ROS production were found in obese vs. non-obese patients. Incubation of the adipose tissue samples and vascular rings with the MAO-A inhibitor (clorgyline, 30 min) improved vascular reactivity and decreased ROS generation. In conclusion, MAO-A is the predominant isoform in human abdominal adipose and vascular tissues, is overexpressed in the setting of inflammation, and contributes to the endothelial dysfunction.

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Systemic Oxidative Stress and Visceral Adipose Tissue Mediators of NLRP3 Inflammasome and Autophagy Are Reduced in Obese Type 2 Diabetic Patients Treated with Metformin

Antioxidants ◽

10.3390/antiox9090892 ◽

2020 ◽

Vol 9 (9) ◽

pp. 892

Author(s):

Zaida Abad-Jiménez ◽

Sandra López-Domènech ◽

Rubén Díaz-Rúa ◽

Francesca Iannantuoni ◽

Segundo Ángel Gómez-Abril ◽

...

Keyword(s):

Oxidative Stress ◽

Adipose Tissue ◽

Visceral Adipose Tissue ◽

Nlrp3 Inflammasome ◽

Molecular Mechanisms ◽

Diabetic Patients ◽

Low Grade ◽

Obese Patients ◽

Visceral Adipose

Obesity is a low-grade inflammatory condition affecting a range of individuals, from metabolically healthy obese (MHO) subjects to type 2 diabetes (T2D) patients. Metformin has been shown to display anti-inflammatory properties, though the underlying molecular mechanisms are unclear. To study whether the effects of metformin are mediated by changes in the inflammasome complex and autophagy in visceral adipose tissue (VAT) of obese patients, a biopsy of VAT was obtained from a total of 68 obese patients undergoing gastric bypass surgery. The patients were clustered into two groups: MHO patients and T2D patients treated with metformin. Patients treated with metformin showed decreased levels of all analyzed serum pro-inflammatory markers (TNFα, IL6, IL1β and MCP1) and a downwards trend in IL18 levels associated with a lower production of oxidative stress markers in leukocytes (mitochondrial ROS and myeloperoxidase (MPO)). A reduction in protein levels of MCP1, NFκB, NLRP3, ASC, ATG5, Beclin1 and CHOP and an increase in p62 were also observed in the VAT of the diabetic group. This downregulation of both the NLRP3 inflammasome and autophagy in VAT may be associated with the improved inflammatory profile and leukocyte homeostasis seen in obese T2D patients treated with metformin with respect to MHO subjects and endorses the cardiometabolic protective effect of this drug.

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Countering adipose tissue dysfunction could underlie the superiority of telmisartan in the treatment of obesity-related hypertension

Cardiovascular Diabetology ◽

10.1186/s12933-021-01259-w ◽

2021 ◽

Vol 20 (1) ◽

Author(s):

Yahya M. Naguib ◽

Rehab M. Samaka ◽

Mohamed S. Rizk ◽

Omnia Ameen ◽

Shaimaa M. Motawea

Keyword(s):

Oxidative Stress ◽

Adipose Tissue ◽

Visceral Adipose Tissue ◽

High Fat Diet ◽

Serum Lipids ◽

High Fat ◽

Diet Induced Obesity ◽

Adipose Tissue Dysfunction ◽

Visceral Adipose ◽

And Oxidative Stress

Abstract Background The prevalence of hypertension and obesity has increased significantly in recent decades. Hypertension and obesity often coexist, and both are associated with increased cardiovascular mortality. Obese hypertensive patients usually require special anti-hypertensive treatment strategy due to the increased risk of treatment resistance. Molecules that can target both obesity and hypertension underlying pathologies should get more attention. Herein, we evaluated the therapeutic effects of telmisartan, with special interest in visceral adipose tissue dysfunction, in obesity-related hypertension rat model. Methods Thirty male Wistar rats weighing 150–200 g were equally divided into: 1—Control group (fed normal laboratory diet for 24 weeks), 2—Diet-induced obesity group (DIO, fed high fat diet for 24 weeks), and 3—Diet-induced obesity treated with telmisartan group (DIO + Tel, fed high fat diet and received telmisartan for 24 weeks). At the end of the study, anthropometrical parameters were evaluated. Systolic blood pressure and heart rate were measured. Blood samples were collected for the measurement of serum lipids, adipokines, cardiac, renal, inflammatory, and oxidative stress biomarkers. Kidneys were removed and used for histopathological studies, and visceral adipose tissue was utilized for histopathological, immunohistochemical and RT-PCR studies. Results High fat diet resulted in obesity-related changes in anthropometrical parameters, elevation of blood pressure, increase in heart rate, higher serum levels of cardiac, inflammatory and kidney function biomarkers, with altered serum lipids, adipokines and oxidative stress markers. Morphological changes (H&E and PAS-stained sections) were noticed in kidneys and visceral adipose tissue. Immunohistochemistry and RT-PCR studies confirmed adipose tissue dysfunction and over-expression of inflammatory and oxidative stress proteins. Telmisartan countered obesity-induced alterations in cardiovascular, renal, and adipose tissue functions. Conclusion Adipose tissue dysfunction could be the core pathophysiology of obesity-related hypertension. Besides its anti-hypertensive effect, telmisartan had profound actions on visceral adipose tissue structure and function. Attention should be given to polymodal molecules targeting adipose tissue-related disorders.

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Visceral Adipose Tissue of Prediabetic and Diabetic Females Shares a Set of Similarly Upregulated microRNAs Functionally Annotated to Inflammation, Oxidative Stress and Insulin Signaling

Antioxidants ◽

10.3390/antiox10010101 ◽

2021 ◽

Vol 10 (1) ◽

pp. 101

Author(s):

Justyna Strycharz ◽

Adam Wróblewski ◽

Andrzej Zieleniak ◽

Ewa Świderska ◽

Tomasz Matyjas ◽

...

Keyword(s):

Oxidative Stress ◽

Adipose Tissue ◽

Visceral Adipose Tissue ◽

Insulin Signaling ◽

Diagnostic Value ◽

Low Grade ◽

Mirnas Expression ◽

Visceral Adipose ◽

And Oxidative Stress

Hypertrophic and hypoxic visceral adipose tissue (VAT) secretes proinflammatory cytokines promoting insulin resistance (IR), prediabetes and type 2 diabetes (T2DM) microRNAs (miRNAs) are markers of metabolic disorders regulating genes critical for e.g., inflammation, glucose metabolism, and antioxidant defense, with raising diagnostic value. The aim of the current study was to evaluate whether hyperglycemia is able to affect the expression of selected miRNAs in VAT of prediabetic (IFG) and diabetic (T2DM) patients vs. normoglycemic (NG) subjects using qPCR. Statistical analyses suggested that miRNAs expression could be sex-dependent. Thus, we determined 15 miRNAs as differentially expressed (DE) among NG, T2DM, IFG females (miR-10a-5p, let-7d-5p, miR-532-5p, miR-127-3p, miR-125b-5p, let-7a-5p, let-7e-5p, miR-199a-3p, miR-365a-3p, miR-99a-5p, miR-100-5p, miR-342-3p, miR-146b-5p, miR-204-5p, miR-409-3p). Majority of significantly changed miRNAs was similarly upregulated in VAT of female T2DM and IFG patients in comparison to NG subjects, positively correlated with FPG and HbA1c, yet, uncorrelated with WHR/BMI. Enrichment analyses indicated involvement of 11 top DE miRNAs in oxidative stress, inflammation and insulin signaling. Those miRNAs expression changes could be possibly associated with low-grade chronic inflammation and oxidative stress in VAT of hyperglycemic subjects.

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Overexpression of hepatic 5α-reductase and 11β-hydroxysteroid dehydrogenase type 1 in visceral adipose tissue is associated with hyperinsulinemia in morbidly obese patients

Metabolism ◽

10.1016/j.metabol.2011.05.001 ◽

2011 ◽

Vol 60 (12) ◽

pp. 1775-1780 ◽

Cited By ~ 25

Author(s):

René Baudrand ◽

José Miguel Domínguez ◽

Cristian A. Carvajal ◽

Arnoldo Riquelme ◽

Carmen Campino ◽

...

Keyword(s):

Adipose Tissue ◽

Visceral Adipose Tissue ◽

Hydroxysteroid Dehydrogenase ◽

Morbidly Obese ◽

Obese Patients ◽

Visceral Adipose

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Excess of visceral adipose tissue with or without aortic elongation leads to a steeper heart position

Acta Radiologica ◽

10.1177/02841851211034053 ◽

2021 ◽

pp. 028418512110340

Author(s):

S Petteri Kauhanen ◽

Petri Saari ◽

Tarmo Korpela ◽

Timo Liimatainen ◽

Ritva Vanninen ◽

...

Keyword(s):

Adipose Tissue ◽

Visceral Adipose Tissue ◽

Interquartile Range ◽

Obese Patients ◽

Aortic Diseases ◽

Clinical Value ◽

Abdominal Aortic ◽

History Of ◽

Axial Ct ◽

Visceral Adipose

Background The heart’s position determined as the heart–aorta angle (HAA) has been demonstrated to associate with ascending aortic (AA) dilatation. Visceral adipose tissue (VAT) and aortic elongation may shift the heart to the steeper position. Purpose To investigate whether VAT and aortic length influence the HAA. Material and Methods We examined 346 consecutive patients (58.4% men; mean age = 67.0 ± 14.1 years) who underwent aortic computed tomography angiography (CTA). HAA was measured as the angle between the long axis of the heart and AA midline. The amount of VAT was measured at the level of middle L4 vertebra from a single axial CT slice. Aortic length was measured by combining four anatomical segments in different CTA images. The amount of VAT and aortic length were determined as mild with values in the lowest quartile and as excessive with values in the other three quartiles. Results A total of 191 patients (55.2%) had no history of aortic diseases, 134 (38.7%) displayed AA dilatation, 8 (2.3%) had abdominal aortic aneurysm (AAA), and 13 (3.8%) had both AA dilatation and AAA. There was a strong nonlinear regression between smaller HAA and VAT/height, and HAA and aortic length/height. Median HAA was 124.2° (interquartile range 119.0°–130.8°) in patients with a mild amount of VAT versus 120.5° (interquartile range 115.4°–124.7°) in patients with excessive VAT ( P < 0.001). Conclusion An excessive amount of VAT and aortic elongation led to a steeper heart position. These aspects may possess clinical value when evaluating aortic diseases in obese patients.

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