Tumor Necrosis Receptor Superfamily Interact with Fusion and Fission of Mitochondria of Adipose Tissue in Obese Patients without Type 2 Diabetes

Interactions between receptors and ligands of the tumor necrosis factor superfamily (TNFSF) provide costimulatory signals that control the survival, proliferation, differentiation, and effector function of immune cells. All components of the TNF superfamily are associated with NF-kB functions that are not limited to cell death and may promote survival in the face of adipose tissue inflammation in obesity. Inflammation dysfunction of mitochondria is a key factor associated with insulin resistance in obesity. The aim of the study was to analyze the relationship of soluble forms of receptors and ligands of the TNF superfamily in blood plasma with mitochondrial dynamics in adipose tissue (greater omentum (GO) and subcutaneous adipose tissue (Sat)) of obese patients with and without type 2 diabetes mellitus (T2DM). Increased plasma sTNF-R1, sTNF-R2, sTNFRSF8 receptors, and ligands TNFSF12, TNFSF13, TNFSF13B are characteristic of obese patients without T2DM. The TNF-a levels in blood plasma were associated with a decrease in MFN2 gene expression in GO and IL-10 in blood plasma. The TNFSF12 levels contributed to a decrease in glucose levels, a decrease in BMI, and an increase in IL-10 levels by influencing the MFN2 gene expression in GO, which supports mitochondrial fusion.

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Tumour Necrosis Receptor Superfamily Interact with the Mitochondrial Dynamics in Adipose Tissue in Obese Patients without Type 2 Diabetes

10.20944/preprints202108.0506.v1 ◽

2021 ◽

Author(s):

Daria Shunkina (Skuratovskaia) ◽

Alexandra Komar ◽

Maria Vulf ◽

Hung Vu Quang ◽

Egor Shunkin ◽

...

Keyword(s):

Type 2 Diabetes ◽

Adipose Tissue ◽

Mitochondrial Dynamics ◽

Greater Omentum ◽

Obese Patients ◽

Tnf Superfamily ◽

The Face ◽

Relationship Of ◽

Subcutaneous Adipose

Interactions between receptors and ligands of the tumor necrosis factor superfamily (TNFSF) provide costimulatory signals that control the survival, proliferation, differentiation, and effector function of immune cells. All components of the TNF superfamily are associated with NF-kB functions that are not limited to cell death and may promote survival in the face of adipose tissue inflammation in obesity. Inflammation and pro-inflammatory dysfunction of mitochondria are key factors associated with insulin resistance in obesity. The aim of the study was to analyze the relationship of soluble forms of receptors and ligands of the TNF superfam-ily in blood plasma with mitochondrial dynamics in adipose tissue (greater omentum (GO) and subcutaneous adipose tissue (Sat)) of obese patients with and without type 2 diabetes mellitus (T2DM). Increased plasma sTNF-R1, sTNF-R2, sTNFRSF8 receptors and ligands TNFSF12, TNFSF13, TNFSF13B are characteristic of obese patients without T2DM. Increases in TNFSF12, TNFSF13B, and sTNF-R1 levels are associated with decreased glucose concentration and decreased BMI in obese patients. The gene expression levels responsible for regulating mitochondrial dynamics were increased in obese patients without T2DM and were unbalanced in patients with obesity and T2DM.

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The chemerin production changes in obese patients with different carbohydrate metabolism state

Biomeditsinskaya Khimiya ◽

10.18097/pbmc20176306582 ◽

2017 ◽

Vol 63 (6) ◽

pp. 582-590 ◽

Cited By ~ 1

Author(s):

M.A. Vasilenko ◽

E.V. Kirienkova ◽

D.A. Skuratovskaya ◽

P.A. Zatolokin ◽

N.I. Mironyuk ◽

...

Keyword(s):

Gene Expression ◽

Type 2 Diabetes ◽

Adipose Tissue ◽

Mrna Expression ◽

Carbohydrate Metabolism ◽

Enzyme Linked Immunosorbent Assay ◽

Control Group ◽

Obese Patients ◽

Tissue Specific

Chemerin is a mediator of adipose tissue involved in the regulation of many processes, including lipogenesis, and inflammatory response. The role of chemerin in the development of insulin resistance has been insufficiently studied and needs detailed understanding. The aim of the study was to investigate chemerin production in obese patients with different states of carbohydrate metabolism. The study included 155 patients with a diagnosis of obesity; 34 patients with overweight. The control group 1 consisted of 43 conditionally healthy donors who did not have obesity. For comparison of the results of a study to determine the levels of tissue-specific mRNA expression of the genes IL-6, TNF-a, RARRES2, (encoding IL-6, TNF-a and chemerin) in adipose tissue introduced a control group 2 – 30 patients without obesity. Study on the relative level of mRNA expression of the genes IL-6, TNF-a and RARRES2 (encoding IL-6, TNF-a and chemerin) was carried out using real time PCR. Concentrations of IL-6, TNF-a, and chemerin were measured in serum/plasma using an enzyme-linked immunosorbent assay (ELISA). We found significant differences in the plasma level of chemerin and tissue-specific features of RARRES2 gene expression in obese patients, depending on the degree of obesity and the state of carbohydrate metabolism. Multidirectional associations of RARRES2 gene expression with TNF-a and IL-6 genes in adipose tissues of different localization are shown: in obese patients (BMI £40 kg/m2) without type 2 diabetes – negative, and type 2 diabetes – positive. Identified relationship chemerin plasma content and the expression level of its gene in biopsies with various parameters of carbohydrate and lipid metabolism, proinflammatory molecules indicate chemerin involved in metabolic and immune processes in obesity.

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CHEMERIN AS A POTENTIAL REGULATOR OF MITOCHONDRIAL QUALITY CONTROL IN OBESE PATIENTS

Medical Immunology (Russia) ◽

10.15789/1563-0625-caa-2227 ◽

2021 ◽

Vol 23 (4) ◽

pp. 881-886

Author(s):

M. A. Vulf ◽

D. A. Shunkina (Skuratovskaia) ◽

V. Hung ◽

A. A. Komar ◽

P. A. Zatolokin ◽

...

Keyword(s):

Type 2 Diabetes ◽

Quality Control ◽

Adipose Tissue ◽

Blood Plasma ◽

Obese Patients ◽

Expression Of Genes ◽

Insulin Dependent ◽

Visceral Adipose ◽

The Relationship

In obese patients, the relationship between the content of chemerin in blood plasma and the expression of genes TFAM, Drp1, MFN2, SOD, BAX, responsible for quality control of mitochondria, in insulin-dependent tissues (adipose tissue, liver) was revealed. The tissue-specific features of gene expression (TFAM, Drp1, MFN2, SOD, BAX), the number of mtDNA copies in the studied depots in obese patients were established. It has been proven that a change (decrease) in the number of mtDNA copies in insulin-dependent tissues can have a protective effect on mitochondria under conditions of increased oxidative stress. It was found that in patients without type 2 diabetes, an increase in chemerin production promotes the activation of the antioxidant system in the visceral adipose tissue but not in the liver. On the contrary, all obese patients with type 2 diabetes showed a decrease (compared with patients without type 2 diabetes) in the plasma level of chemerin. Thus, the low content of chemerin in the blood plasma in patients with type 2 diabetes mediates the formation of mitochondrial dysfunction in insulin-dependent tissues (adipose tissue, liver).

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Analysis of gene expression profiles in insulin-sensitive tissues from pre-diabetic and diabetic Zucker diabetic fatty rats

Journal of Molecular Endocrinology ◽

10.1677/jme.1.01679 ◽

2005 ◽

Vol 34 (2) ◽

pp. 299-315 ◽

Cited By ~ 42

Author(s):

Young Ho Suh ◽

Younyoung Kim ◽

Jeong Hyun Bang ◽

Kyoung Suk Choi ◽

June Woo Lee ◽

...

Keyword(s):

Gene Expression ◽

Insulin Resistance ◽

Type 2 Diabetes ◽

Skeletal Muscle ◽

Adipose Tissue ◽

Expression Profiles ◽

Gene Expression Profiles ◽

Zucker Diabetic Fatty Rats ◽

Zdf Rats

Insulin resistance occurs early in the disease process, preceding the development of type 2 diabetes. Therefore, the identification of molecules that contribute to insulin resistance and leading up to type 2 diabetes is important to elucidate the molecular pathogenesis of the disease. To this end, we characterized gene expression profiles from insulin-sensitive tissues, including adipose tissue, skeletal muscle, and liver tissue of Zucker diabetic fatty (ZDF) rats, a well characterized type 2 diabetes animal model. Gene expression profiles from ZDF rats at 6 weeks (pre-diabetes), 12 weeks (diabetes), and 20 weeks (late-stage diabetes) were compared with age- and sex-matched Zucker lean control (ZLC) rats using 5000 cDNA chips. Differentially regulated genes demonstrating > 1.3-fold change at age were identified and categorized through hierarchical clustering analysis. Our results showed that while expression of lipolytic genes was elevated in adipose tissue of diabetic ZDF rats at 12 weeks of age, expression of lipogenic genes was decreased in liver but increased in skeletal muscle of 12 week old diabetic ZDF rats. These results suggest that impairment of hepatic lipogenesis accompanied with the reduced lipogenesis of adipose tissue may contribute to development of diabetes in ZDF rats by increasing lipogenesis in skeletal muscle. Moreover, expression of antioxidant defense genes was decreased in the liver of 12-week old diabetic ZDF rats as well as in the adipose tissue of ZDF rats both at 6 and 12 weeks of age. Cytochrome P450 (CYP) genes were also significantly reduced in 12 week old diabetic liver of ZDF rats. Genes involved in glucose utilization were downregulated in skeletal muscle of diabetic ZDF rats, and the hepatic gluconeogenic gene was upregulated in diabetic ZDF rats. Genes commonly expressed in all three tissue types were also observed. These profilings might provide better fundamental understanding of insulin resistance and development of type 2 diabetes.

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The roles of apo E genotype, gender and adipokines in blood plasma lipids in Caucasians with well-controlled type 2 diabetes

International Journal of Diabetes and Metabolism ◽

10.1159/000497692 ◽

2010 ◽

Vol 18 (2) ◽

pp. 49-54

Author(s):

Douglas E. Barre D.E. ◽

Kazimiera A. Mizier-Barre K.A. ◽

Odette Griscti O. ◽

Kevin Hafez K.

Keyword(s):

Type 2 Diabetes ◽

Blood Plasma ◽

Plasma Lipids ◽

Apo E ◽

Apo E Genotype ◽

In Blood Plasma

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Improved skeletal muscle oxidative enzyme activity and restoration of PGC-1α and PPARβ/δ gene expression upon rosiglitazone treatment in obese patients with type 2 diabetes mellitus

International Journal of Obesity ◽

10.1038/sj.ijo.0803567 ◽

2007 ◽

Vol 31 (8) ◽

pp. 1302-1310 ◽

Cited By ~ 113

Author(s):

M Mensink ◽

M K C Hesselink ◽

A P Russell ◽

G Schaart ◽

J-P Sels ◽

...

Keyword(s):

Gene Expression ◽

Diabetes Mellitus ◽

Type 2 Diabetes ◽

Skeletal Muscle ◽

Type 2 Diabetes Mellitus ◽

Enzyme Activity ◽

Obese Patients ◽

Oxidative Enzyme Activity ◽

Rosiglitazone Treatment

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The Effect of Very-Low-Calorie Diet on mRNA Expression of Inflammation-Related Genes in Subcutaneous Adipose Tissue and Peripheral Monocytes of Obese Patients with Type 2 Diabetes Mellitus

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jc.2010-1858 ◽

2011 ◽

Vol 96 (4) ◽

pp. E606-E613 ◽

Cited By ~ 40

Author(s):

M. Mraz ◽

Z. Lacinova ◽

J. Drapalova ◽

D. Haluzikova ◽

A. Horinek ◽

...

Keyword(s):

Diabetes Mellitus ◽

Type 2 Diabetes ◽

Adipose Tissue ◽

Mrna Expression ◽

Obese Patients ◽

Very Low Calorie Diet ◽

Low Calorie Diet ◽

Calorie Diet ◽

Proinflammatory Factors

Abstract Context: Low-grade inflammation links obesity, type 2 diabetes mellitus (T2DM), and cardiovascular diseases. Objective: To explore the expression profile of genes involved in inflammatory pathways in adipose tissue and peripheral monocytes (PM) of obese patients with and without T2DM at baseline and after dietary intervention. Design: Two-week intervention study with very-low-calorie diet (VLCD). Setting: University hospital. Patients: Twelve obese females with T2DM, 8 obese nondiabetic females (OB) and 15 healthy age-matched females. Intervention: Two weeks of VLCD (2500 kJ/d). Main Outcome Measures: Metabolic parameters, circulating cytokines, hormones, and mRNA expression of 39 genes in sc adipose tissue (SCAT) and PM. Results: Both T2DM and OB group had significantly increased serum concentrations of circulating proinflammatory factors (C-reactive protein, TNFα, IL-6, IL-8), mRNA expression of macrophage antigen CD68 and proinflammatory chemokines (CCL-2, -3, -7, -8, -17, -22) in SCAT and complementary chemokine receptors (CCR-1, -2, -3, -5) and other proinflammatory receptors (toll-like receptor 2 and 4, TNF receptor superfamily 1A and 1B, IL-6R) in PM, with OB group showing less pronounced chemoattracting and proinflammatory profile compared to T2DM group. In T2DM patients VLCD decreased body weight, improved metabolic profile, and decreased mRNA expression of up-regulated CCRs in PM and chemokines [CCL 8, chemokine (C-X-C motif) ligand 10] in SCAT. VLCD markedly increased mRNA expression of T-lymphocyte attracting chemokine CCL-17 in SCAT. Conclusion: Obese patients with and without T2DM have increased mRNA expression of chemotactic and proinflammatory factors in SCAT and expression of corresponding receptors in PM. Two weeks of VLCD significantly improved this profile in T2DM patients.

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