scholarly journals A Transcriptomic and Proteomic Atlas of Obesity and Type 2 Diabetes in Cynomolgus Monkeys

2021 ◽  
Author(s):  
Xianglong Zhang ◽  
Ying Lei ◽  
Oliver Homann ◽  
Marina Stolina ◽  
Songli Wang ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Immune Response ◽  
Nonhuman Primate ◽  
Metabolic Disorders ◽  
Healthy Controls ◽  
Adipose Tissues ◽  
Cynomolgus Monkeys ◽  
Single Cell Rna Sequencing

Obesity and type 2 diabetes (T2D) remain major global healthcare challenges and developing therapeutics necessitate using nonhuman primate models. Here, we present transcriptomic and proteomic analyses of all the major organs of cynomolgus monkeys with spontaneous obesity or T2D in comparison to healthy controls. Molecular changes occur predominantly in the adipose tissues of individuals with obesity, while extensive expression perturbations among T2D individuals are observed in many tissues, such as the liver, kidney, brain, and heart. Immune response-related pathways are upregulated in obesity and T2D, whereas metabolism and mitochondrial pathways are downregulated. Incorporating human single-cell RNA sequencing findings corroborates the role of macrophages and monocytes in obesity. Moreover, we highlight some potential therapeutic targets including SLC2A1 and PCSK1 in obesity as well as SLC30A8 and SLC2A2 in T2D. Our findings provide insights into tissue-specific molecular foundations of obesity and T2D and reveal the mechanistic links between these two metabolic disorders.

scholarly journals Potential Roles of Adipocyte Extracellular Vesicle–Derived miRNAs in Obesity-Mediated Insulin Resistance

2020 ◽  
Author(s):  
Yujeong Kim ◽  
Ok-Kyung Kim
Keyword(s):  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Adipose Tissue ◽  
Signaling Pathway ◽  
Insulin Signaling ◽  
Metabolic Disorders ◽  
Extracellular Vesicle ◽  
Extracellular Mirnas

ABSTRACT Recently, extracellular microRNAs (miRNAs) from adipose tissue have been shown to be involved in the development of insulin resistance. Here, we summarize several mechanisms explaining the pathogenesis of obesity-induced insulin resistance and associated changes in the expression of obesity-associated extracellular miRNAs. We discuss how miRNAs, particularly miR-27a, miR-34a, miR-141-3p, miR-155, miR210, and miR-222, in extracellular vesicles secreted from the adipose tissue can affect the insulin signaling pathway in metabolic tissue. Understanding the role of these miRNAs will further support the development of therapeutics for obesity and metabolic disorders such as type 2 diabetes.

scholarly journals Type 2 Diabetes Mellitus Associated with Obesity (Diabesity). The Central Role of Gut Microbiota and Its Translational Applications

Nutrients ◽  
2020 ◽  
Vol 12 (9) ◽  
pp. 2749 ◽  
Author(s):  
Miguel A. Ortega ◽  
Oscar Fraile-Martínez ◽  
Irene Naya ◽  
Natalio García-Honduvilla ◽  
Melchor Álvarez-Mon ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Gut Microbiota ◽  
Metabolic Disorders ◽  
Health Concern ◽  
Public Health Concern ◽  
Wide Range

Obesity is a condition of rising prevalence worldwide, with important socioeconomic implications, being considered as a growing public health concern. Frequently, obesity brings other complications in addition to itself—like Type 2 Diabetes Mellitus (T2DM)—sharing origin, risk factors and pathophysiological mechanisms. In this context, some authors have decided to include both conditions as a unique entity known as “diabesity”. In fact, understanding diabesity as a single disease is possible to maximise the benefits from therapies received in these patients. Gut microbiota plays a key role in individual’s health, and their alterations, either in its composition or derived products are related to a wide range of metabolic disorders like T2DM and obesity. The present work aims to collect the different changes reported in gut microbiota in patients with T2DM associated with obesity and their possible role in the onset, development, and establishment of the disease. Moreover, current research lines to modulate gut microbiota and the potential clinical translation derived from the knowledge of this system will also be reviewed, which may provide support for a better clinical management of such a complex condition.

scholarly journals Diabetes Mellitus and Its Metabolic Complications: The Role of Adipose Tissues

2021 ◽  
Vol 22 (14) ◽  
pp. 7644
Author(s):  
Lowell Dilworth ◽  
Aldeam Facey ◽  
Felix Omoruyi
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Insulin Release ◽  
Endocrine Function ◽  
Metabolic Dysfunction ◽  
Metabolic Complications ◽  
Adipose Tissues ◽  
Fat Storage

Many approaches have been used in the effective management of type 2 diabetes mellitus. A recent paradigm shift has focused on the role of adipose tissues in the development and treatment of the disease. Brown adipose tissues (BAT) and white adipose tissues (WAT) are the two main types of adipose tissues with beige subsets more recently identified. They play key roles in communication and insulin sensitivity. However, WAT has been shown to contribute significantly to endocrine function. WAT produces hormones and cytokines, collectively called adipocytokines, such as leptin and adiponectin. These adipocytokines have been proven to vary in conditions, such as metabolic dysfunction, type 2 diabetes, or inflammation. The regulation of fat storage, energy metabolism, satiety, and insulin release are all features of adipose tissues. As such, they are indicators that may provide insights on the development of metabolic dysfunction or type 2 diabetes and can be considered routes for therapeutic considerations. The essential roles of adipocytokines vis-a-vis satiety, appetite, regulation of fat storage and energy, glucose tolerance, and insulin release, solidifies adipose tissue role in the development and pathogenesis of diabetes mellitus and the complications associated with the disease.

scholarly journals Human Visceral Adipose Tissue (VAT) Inflammation Is Not Associated With Perforin Deficiency in Type 2 Diabetes Mellitus (DM) Subjects as Compared to Health Controls

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A15-A16
Author(s):  
Ravindra Kumar Shukla ◽  
Ramkaran Choudhary ◽  
Mahendra Lodha ◽  
Mahaveer singh Rodha ◽  
Nitin Bajpai ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
T Cell ◽  
Nk Cells ◽  
Single Cell ◽  
Stromal Vascular Fraction ◽  
Healthy Controls ◽  
Type 2 Dm ◽  
And Control

Abstract Introduction: Role of T cells in VAT inflammation is poorly characterised. Perforin deficiency is associated with autoimmune inflammatory diseases like Hemophagocytosis Lymphohistiocytosis,as also in context of type 1 DM pathogenesis. Data from animal models suggest that perforin deficiency leads to VAT inflammation1Objective: We hypothesized CD8+/perf+ and CD56+/perf+ cells to be decreased in type 2 DM as compared to healthy controls. The present study also explored the difference in activation of T/NK cells between two groups Methods: 2×2 cm omental tissue was obtained from subjects undergoing elective abdominal surgery. The sample was transported in RPMI solution and stored in -80 ℃. Processing involved thawing, incubation at 37.6 ℃ for 24 hours with type IV Collagenase (1 mg/ml, Sigma Aldrich) 1ml/g of tissue,centrifuge (32g for 10 min at 10℃). The resultant Stromal Vascular fraction (SVF) was suspended in phosphate buffer saline (PBS), passed through cell strainer to make single cell suspension. It was again centrifuged and tagged with CD markers of interest. Fc block was added and single cell solution with FACS fluid prepared. It was run in BD CANTO-2 flow cytometer as described2Results: Of seventeen samples analysed, twelve samples of type 2 diabetes subjects were compared with five healthy controls. All results are presented in median. The diabetics had higher HbA1c (8.1 % vs 6%), higher BMI (28 kg/m2 vs 24 kg/m2), hsCRP(2.1 mg/dl Vs 0.9 mg/dl) but there was no difference in HOMA-Ir (5 vs 5.2 mU/L/mg/dl). The percentage of CD4+ + CD8+ cells/g of VAT was similar in both cases and control (20 × 103 Vs 23× 103). CD8+/CD45+/perf+ and CD56+/CD45+/perf+ could not be identified in any of the samples. Although CD8+/CD45+/perf-- and CD56+/CD45+/perf-- cells were identified. Next, we analysed the same cells for cytotoxic activation by 107a. The percentage of 107a positivity was low in CD 8+ (7% and 4 % respectively in cases and control) and CD 56+ cells (10% and 9 % respectively in cases and control),Although clinically type 2 DM subjects were obese and had inflammation (i.e higher hsCRP), there was no difference in VAT activation of immune cells studied. Also, we could not delineate perforin in any of the samples. Conclusion: Taken together this work suggests VAT T cell immune milieu in human Type 2 DM is different from mouse model. It is neither characterised by perforin deficiency nor activation of T cell/NK cell. This study points towards the probability that, the role of T cell/NK cells in human VAT infiltration could be fundamentally different from mice models. Further studies should be focussed on functional characteristics of these cells and interaction with VAT macrophages. References 1. Xavier S. Revelo et al Diabetes 2015;64:90–103 2. Wetzels S et al J Vis Exp. 2018 Mar 6;(133):57319.

scholarly journals Recruitment of Thermogenic Fat: Trigger of Fat Burning

2021 ◽  
Vol 12 ◽  
Author(s):  
Zhihan Wang ◽  
Xuefeng Yu ◽  
Yong Chen
Keyword(s):  
Type 2 Diabetes ◽  
Fatty Acids ◽  
Metabolic Disorders ◽  
Mitochondrial Oxidative Phosphorylation ◽  
Adipose Tissues ◽  
Adaptive Thermogenesis ◽  
Beige Adipocytes ◽  
Novel Therapeutic ◽  
Thermogenic Capacity

Brown and beige adipose tissues possess the remarkable capacity to convert energy into heat, which potentially opens novel therapeutic perspectives targeting the epidemic of metabolic syndromes such as obesity and type 2 diabetes. These thermogenic fats implement mitochondrial oxidative phosphorylation and uncouple respiration to catabolize fatty acids and glucose, which leads to an increase in energy expenditure. In particular, beige adipocytes that arise in white adipose tissue display their thermogenic capacity through various noncanonical mechanisms. This review aims to summarize the general overview of thermogenic fat, especially including the UCP1-independent adaptive thermogenesis and the emerging mechanisms of “beiging”, which may provide more evidence of targeting thermogenic fat to counteract obesity and other metabolic disorders in humans.

scholarly journals Role of Gut Microbiome on Metabolic Disorders

2020 ◽  
pp. 21-35
Author(s):  
Ifeanyi O. Oshim ◽  
Nneka R. Agbakoba ◽  
Evelyn U. Urama ◽  
Oluwayemisi Odeyemi ◽  
Nkechi A. Olise ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Adipose Tissue ◽  
Intestinal Permeability ◽  
Visceral Adipose Tissue ◽  
Gut Microbiome ◽  
Metabolic Disorders ◽  
Ppar Γ ◽  
Visceral Adipose

Microbiome that reside in the human gut are key contributors to host metabolism and are considered potential sources of novel therapeutics in metabolic disorders. This review discusses the role of gut microbiome in the pathogenesis of obesity, type 2 diabetes mellitus (T2DM), chronic kidney disease and cardiovascular disease. Gut microbiome remains quite stable, although changes take place between birth and adulthood due to external influences, such as diet, disease and environment. Understanding these changes is important to predict diseases and develop therapies. In gut heamostasis, Gut microbiome converts high fibres intake into short-chain fatty acids like butyrate, propionate and acetate which normalize intestinal permeability and alter de novo lipogenesis and gluconeogenesis through reduction of free fatty acid production by visceral adipose tissue. This effect contributes to reduce food intake and to improve glucose metabolism. Propionate can also bind to G protein coupled receptors (GPR)-43 expressed on lymphocytes in order to maintain appropriate immune defence. Butyrate activates peroxisome proliferator-activated receptor-γ (PPAR-γ) leading to beta-oxidation and oxygen consumption, a phenomenon contributing to maintain anaerobic condition in the gut lumen. In contrast, diets most especially western diet consisting among others of high fat and high salt content has been reported to cause gut dysbiosis. This alteration of gut microbiome result to chronic bacterial translocation and increased intestinal permeability that can drive a systemic inflammation leading to macrophage influx into visceral adipose tissue, activation of hepatic kuffer cells and insulin resistance in type 2 diabetes. This effect contributes to lower mucus thickness, decrease butyrate and propionate producing bacteria, L-cells secrete less gut peptides, lack of PPAR-γ activation lead to higher oxygen available for the microbiome at the proximity of the mucosa and increases the proliferation of Enterobacteriaceae with commensurate increase in opportunistic pathogens. However, Gut microbiome are major biomarker for early prognosis of diabetes and other metabolic disorders.

scholarly journals AB0083 STUDY OF THE ROLE OF ANGIOPOIETIN-LIKE PROTEIN TYPE 4 IN METABOLIC DISORDERS CAUSED BY INFLAMMATION IN RHEUMATOID ARTHRITIS

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1341.2-1341
Author(s):  
A. Aleksandrov ◽  
V. Aleksandrov ◽  
L. Shilova
Keyword(s):  
Rheumatoid Arthritis ◽  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Metabolic Syndrome ◽  
Blood Serum ◽  
Disease Activity ◽  
Metabolic Disorders ◽  
Healthy Individuals

Background:Objectives:To assess the potential role of angiopoietin-like protein type 4 (ANGPTL4) in metabolic disorders caused by inflammation in rheumatoid arthritis (RA).Methods:The study included 88 patients with significant RA, 64 patients with other rheumatic diseases (RD) (36 patients with osteoarthritis (OA); 28 patients with psoriatic arthritis (PsA); 17 patients with ankylosing spondylitis (AS)) and 32 healthy individuals. Estimation of ANGPTL4 was carried out by enzyme immunoassay using the commercial test system “RayBio Human ANGPTL4 ELISA Kit” (RayBiotech, USA) in blood serum. Levels of ESR, CRP, RF, antibodies to cyclic citrullinated peptide (anti-CCP) and modified vimentin (anti-MCV) in the ELISA test were determined for all patients with RA.Results:The level of ANGPTL4 in the blood serum of patients with RA was significantly higher than in healthy people (p <0.001) and patients with other RD (p = 0.012 compared with OA; p = 0.046 with PsA; p = 0.008 with AS). ANGPTL4 indices in patients with RA correlated with the age of onset of RA (r = -0.658, p <0.001), disease activity according to DAS-28 (r = 0.449, p = 0.001), level of education (r = 0.235, p = 0.029), dose of glucocorticoid hormones (r = 0.321, p = 0.009) and methotrexate (r = -0.496, p = 0.05), the presence of osteopenia (r = 0.44), signs of kidney damage - proteinuria (r = 0.309, p = 0.037) and hypoalbuminemia (r = 0.386, p = 0.022), as well as with CRP levels (r = 0.488, p = 0.003), ESR (r = 0.458, p = 0.002), serum vitamin D (r = -0.417) and urinary calcium when recalculated to creatinine (r = 0.797, p = 0.032).Patients with RA showed a high frequency of insulin resistance (according to the HOMA-IR index) (1.27 [0.84–1.62] in patients with RA; 0.76 [0.44–1.02] in healthy individuals; p <0.001) and the presence of coronary heart disease, as well as a positive correlation between disease activity (according to DAS-28) and insulin resistance (according to the HOMA-IR index) (p = 0.033).Higher values of C-reactive protein (p = 0.04) and serum ANGPTL4 levels (p = 0.042, compared with patients with RA without type 2 diabetes; p = 0.026, compared with healthy individuals) were determined in the group of patients with RA with the presence of type 2 diabetes. ANGPTL4 acts as an inhibitor of lipoprotein lipase. His contribution to the development of dyslipidemia in RA can be demonstrated by the results we obtained when comparing groups of patients with / without signs of metabolic syndrome (MS). A positive correlation between ANGPTL4 and triglyceride levels (r = 0.42, p = 0.018) was found. An increase in the level of ANGPTL4 in blood serum of patients with RA with MS (p = 0.027 compared with RA without MS) can predict the development of cardiac pathology in this group of patients.Conclusion:ANGPTL4 is directly involved in the regulation of glucose homeostasis, lipid metabolism, and insulin sensitivity. Cardiovascular diseases associated with atherosclerosis, insulin resistance and metabolic syndrome are known as the most common extraarticular manifestations of RA; the study of the role of ANGPTL4 in metabolic disorders caused by inflammation can show a new direction in the development of laboratory and therapeutic technologies in RA.Disclosure of Interests:None declared

scholarly journals Role of mTOR in Glucose and Lipid Metabolism

2018 ◽  
Vol 19 (7) ◽  
pp. 2043 ◽  
Author(s):  
Zhuo Mao ◽  
Weizhen Zhang
Keyword(s):  
Type 2 Diabetes ◽  
Growth Factors ◽  
Lipid Metabolism ◽  
Mammalian Target Of Rapamycin ◽  
Adipose Tissues ◽  
Glucose And Lipid Metabolism ◽  
Pathological Conditions ◽  
Pharmacological Targets

The mammalian target of rapamycin, mTOR is the master regulator of a cell’s growth and metabolic state in response to nutrients, growth factors and many extracellular cues. Its dysregulation leads to a number of metabolic pathological conditions, including obesity and type 2 diabetes. Here, we review recent findings on the role of mTOR in major metabolic organs, such as adipose tissues, liver, muscle, pancreas and brain. And their potentials as the mTOR related pharmacological targets will be also discussed.

scholarly journals The role of inflammation in the development of metabolic disorders in patients with arterial hypertension

2019 ◽  
Vol 34 (3) ◽  
pp. 45-52
Author(s):  
L. V. Zhuravlyova ◽  
M. V. Kulikova
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Arterial Hypertension ◽  
Metabolic Disorders ◽  
Developed Countries ◽  
The World ◽  
The Developed Countries

In recent years, the comorbid course of cardiovascular diseases, primarily arterial hypertension with impaired carbohydrate tolerance or type 2 diabetes mellitus, is becoming increasingly important in the developed countries of the world. In this regard, the need for a more detailed study of the general mechanisms of the development of arterial hypertension, pre-diabetes, and type 2 diabetes mellitus, namely inflammation, is increasing. There are many studies that investigate the role of inflammation in hypertension and associated glucometabolic disorders, but the exact mechanisms by which activated immune cells lead to the development and maintenance of these conditions remain to be seen. Obtaining new data in this area may contribute to a deeper understanding of cardiometabolic disorder pathogenesis. It may allow to predict the progression of these disorders at the early stages and to develop effective preventive and therapeutic tactics for their correction.

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