scholarly journals Adipocyte, Immune Cells, and miRNA Crosstalk: A Novel Regulator of Metabolic Dysfunction and Obesity

Cells ◽  
2021 ◽  
Vol 10 (5) ◽  
pp. 1004
Author(s):  
Sonia Kiran ◽  
Vijay Kumar ◽  
Santosh Kumar ◽  
Robert L Price ◽  
Udai P. Singh
Keyword(s):  
Insulin Resistance ◽  
Immune Response ◽  
T Cells ◽  
Immune Cells ◽  
Metabolic Diseases ◽  
Liver Disorder ◽  
Low Grade ◽  
Peripheral Tissues ◽  
Nonalcoholic Fatty Liver ◽  
Cytokines And Chemokines

Obesity is characterized as a complex and multifactorial excess accretion of adipose tissue (AT) accompanied with alterations in the immune response that affects virtually all age and socioeconomic groups around the globe. The abnormal accumulation of AT leads to several metabolic diseases, including nonalcoholic fatty liver disorder (NAFLD), low-grade inflammation, type 2 diabetes mellitus (T2DM), cardiovascular disorders (CVDs), and cancer. AT is an endocrine organ composed of adipocytes and immune cells, including B-Cells, T-cells and macrophages. These immune cells secrete various cytokines and chemokines and crosstalk with adipokines to maintain metabolic homeostasis and low-grade chronic inflammation. A novel form of adipokines, microRNA (miRs), is expressed in many developing peripheral tissues, including ATs, T-cells, and macrophages, and modulates the immune response. miRs are essential for insulin resistance, maintaining the tumor microenvironment, and obesity-associated inflammation (OAI). The abnormal regulation of AT, T-cells, and macrophage miRs may change the function of different organs including the pancreas, heart, liver, and skeletal muscle. Since obesity and inflammation are closely associated, the dysregulated expression of miRs in inflammatory adipocytes, T-cells, and macrophages suggest the importance of miRs in OAI. Therefore, in this review article, we have elaborated the role of miRs as epigenetic regulators affecting adipocyte differentiation, immune response, AT browning, adipogenesis, lipid metabolism, insulin resistance (IR), glucose homeostasis, obesity, and metabolic disorders. Further, we will discuss a set of altered miRs as novel biomarkers for metabolic disease progression and therapeutic targets for obesity.

scholarly journals The Liver as an Endocrine Organ—Linking NAFLD and Insulin Resistance

2019 ◽  
Vol 40 (5) ◽  
pp. 1367-1393 ◽  
Author(s):  
Matthew J Watt ◽  
Paula M Miotto ◽  
William De Nardo ◽  
Magdalene K Montgomery
Keyword(s):  
Insulin Resistance ◽  
Lipid Metabolism ◽  
Liver Disorder ◽  
The Body ◽  
Limited Information ◽  
Peripheral Tissues ◽  
Nonalcoholic Fatty Liver ◽  
Induce Insulin Resistance ◽  
Glucose And Lipid Metabolism ◽  
Physiological Processes

AbstractThe liver is a dynamic organ that plays critical roles in many physiological processes, including the regulation of systemic glucose and lipid metabolism. Dysfunctional hepatic lipid metabolism is a cause of nonalcoholic fatty liver disease (NAFLD), the most common chronic liver disorder worldwide, and is closely associated with insulin resistance and type 2 diabetes. Through the use of advanced mass spectrometry “omics” approaches and detailed experimentation in cells, mice, and humans, we now understand that the liver secretes a wide array of proteins, metabolites, and noncoding RNAs (miRNAs) and that many of these secreted factors exert powerful effects on metabolic processes both in the liver and in peripheral tissues. In this review, we summarize the rapidly evolving field of “hepatokine” biology with a particular focus on delineating previously unappreciated communication between the liver and other tissues in the body. We describe the NAFLD-induced changes in secretion of liver proteins, lipids, other metabolites, and miRNAs, and how these molecules alter metabolism in liver, muscle, adipose tissue, and pancreas to induce insulin resistance. We also synthesize the limited information that indicates that extracellular vesicles, and in particular exosomes, may be an important mechanism for intertissue communication in normal physiology and in promoting metabolic dysregulation in NAFLD.

scholarly journals Nutritional approaches for managing obesity-associated metabolic diseases

2017 ◽  
Vol 233 (3) ◽  
pp. R145-R171 ◽  
Author(s):  
Rachel Botchlett ◽  
Shih-Lung Woo ◽  
Mengyang Liu ◽  
Ya Pei ◽  
Xin Guo ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Insulin Sensitivity ◽  
Metabolic Pathways ◽  
Metabolic Diseases ◽  
Critical Role ◽  
Fat Deposition ◽  
Low Grade ◽  
Metabolic Homeostasis ◽  
Peripheral Tissues ◽  
Metabolic Dysregulation

Obesity is an ongoing pandemic and serves as a causal factor of a wide spectrum of metabolic diseases including diabetes, fatty liver disease, and cardiovascular disease. Much evidence has demonstrated that nutrient overload/overnutrition initiates or exacerbates inflammatory responses in tissues/organs involved in the regulation of systemic metabolic homeostasis. This obesity-associated inflammation is usually at a low-grade and viewed as metabolic inflammation. When it exists continuously, inflammation inappropriately alters metabolic pathways and impairs insulin signaling cascades in peripheral tissues/organs such as adipose tissue, the liver and skeletal muscles, resulting in local fat deposition and insulin resistance and systemic metabolic dysregulation. In addition, inflammatory mediators, e.g., proinflammatory cytokines, and excessive nutrients, e.g., glucose and fatty acids, act together to aggravate local insulin resistance and form a vicious cycle to further disturb the local metabolic pathways and exacerbate systemic metabolic dysregulation. Owing to the critical role of nutrient metabolism in controlling the initiation and progression of inflammation and insulin resistance, nutritional approaches have been implicated as effective tools for managing obesity and obesity-associated metabolic diseases. Based on the mounting evidence generated from both basic and clinical research, nutritional approaches are commonly used for suppressing inflammation, improving insulin sensitivity, and/or decreasing fat deposition. Consequently, the combined effects are responsible for improvement of systemic insulin sensitivity and metabolic homeostasis.

scholarly journals The immune response of T cells and therapeutic targets related to regulating the levels of T helper cells after ischaemic stroke

2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Tian-Yu Lei ◽  
Ying-Ze Ye ◽  
Xi-Qun Zhu ◽  
Daniel Smerin ◽  
Li-Juan Gu ◽  
...  
Keyword(s):  
Immune Response ◽  
T Cells ◽  
Immune System ◽  
Immune Responses ◽  
Ischaemic Stroke ◽  
Immune Cells ◽  
Tissue Injury ◽  
Recovery Period ◽  
Vital Functions ◽  
Anti Inflammatory

AbstractThrough considerable effort in research and clinical studies, the immune system has been identified as a participant in the onset and progression of brain injury after ischaemic stroke. Due to the involvement of all types of immune cells, the roles of the immune system in stroke pathology and associated effects are complicated. Past research concentrated on the functions of monocytes and neutrophils in the pathogenesis of ischaemic stroke and tried to demonstrate the mechanisms of tissue injury and protection involving these immune cells. Within the past several years, an increasing number of studies have elucidated the vital functions of T cells in the innate and adaptive immune responses in both the acute and chronic phases of ischaemic stroke. Recently, the phenotypes of T cells with proinflammatory or anti-inflammatory function have been demonstrated in detail. T cells with distinctive phenotypes can also influence cerebral inflammation through various pathways, such as regulating the immune response, interacting with brain-resident immune cells and modulating neurogenesis and angiogenesis during different phases following stroke. In view of the limited treatment options available following stroke other than tissue plasminogen activator therapy, understanding the function of immune responses, especially T cell responses, in the post-stroke recovery period can provide a new therapeutic direction. Here, we discuss the different functions and temporal evolution of T cells with different phenotypes during the acute and chronic phases of ischaemic stroke. We suggest that modulating the balance between the proinflammatory and anti-inflammatory functions of T cells with distinct phenotypes may become a potential therapeutic approach that reduces the mortality and improves the functional outcomes and prognosis of patients suffering from ischaemic stroke.

scholarly journals Effect of Salivary Exosomal miR-25-3p on Periodontitis With Insulin Resistance

2022 ◽  
Vol 12 ◽  
Author(s):  
Jin-Seok Byun ◽  
Ho Yeop Lee ◽  
Jingwen Tian ◽  
Ji Sun Moon ◽  
Jaejin Choi ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
T Cells ◽  
Immune Cells ◽  
Γδ T Cells ◽  
Healthy Individuals ◽  
Local Inflammation ◽  
Diet Induced Obesity ◽  
Exosomal Mirna

Periodontitis is caused by an oral microbial dysbiosis-mediated imbalance of the local immune microenvironment, which is promoted by insulin resistance and obesity. The prevalence and severity of periodontitis is higher in patients with type 2 diabetes than in healthy individuals, possibly because of differences in immune responses. The level of glycemic control also affects the saliva profile, which may further promote periodontal disease in diabetes patients. Therefore, we compared the salivary exosomal miRNA profiles of patients with type 2 diabetes with those of healthy individuals, and we found that exosomal miR-25-3p in saliva is significantly enriched (by approximately 2-fold, p < 0.01) in obese patients with type 2 diabetes. We also identified CD69 mRNA as a miR-25-3p target that regulates both activation of γδ T cells and the inflammatory response. Knockdown of CD69 increased (by approximately 2-fold) interleukin-17A production of γδ T cells in vitro. To evaluate the role of exosomal miRNA on progression of periodontitis, we analyzed regional immune cells in both periodontal tissues and lymph nodes from mice with periodontitis. We found that diet-induced obesity increased the population of infiltrating pro-inflammatory immune cells in the gingiva and regional lymph nodes of these mice. Treatment with miR-25-3p inhibitors prevented the local in vivo inflammatory response in mice with periodontitis and diet-induced obesity. Finally, we showed that suppression of interleukin 17-mediated local inflammation by a miR-25-3p inhibitor alleviated (by approximately 34%) ligature-induced periodontal alveolar bone loss in mice. Taken together, these data suggest that exosomal miR-25-3p in saliva contributes to development and progression of diabetes-associated periodontitis. Discovery of additional miR-25-3p targets may provide critical insights into developing drugs to treat periodontitis by regulating γδ T cell-mediated local inflammation.

scholarly journals Disrupting phosphatase SHP2 in macrophages protects mice from high-fat diet-induced hepatic steatosis and insulin resistance by elevating IL-18 levels

2020 ◽  
Vol 295 (31) ◽  
pp. 10842-10856 ◽  
Author(s):  
Wen Liu ◽  
Ye Yin ◽  
Meijing Wang ◽  
Ting Fan ◽  
Yuyu Zhu ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Hepatic Steatosis ◽  
High Fat Diet ◽  
Metabolic Disorders ◽  
Metabolic Diseases ◽  
Low Grade ◽  
High Fat ◽  
Caspase 1

Chronic low-grade inflammation plays an important role in the pathogenesis of type 2 diabetes. Src homology 2 domain-containing tyrosine phosphatase-2 (SHP2) has been reported to play diverse roles in different tissues during the development of metabolic disorders. We previously reported that SHP2 inhibition in macrophages results in increased cytokine production. Here, we investigated the association between SHP2 inhibition in macrophages and the development of metabolic diseases. Unexpectedly, we found that mice with a conditional SHP2 knockout in macrophages (cSHP2-KO) have ameliorated metabolic disorders. cSHP2-KO mice fed a high-fat diet (HFD) gained less body weight and exhibited decreased hepatic steatosis, as well as improved glucose intolerance and insulin sensitivity, compared with HFD-fed WT littermates. Further experiments revealed that SHP2 deficiency leads to hyperactivation of caspase-1 and subsequent elevation of interleukin 18 (IL-18) levels, both in vivo and in vitro. Of note, IL-18 neutralization and caspase-1 knockout reversed the amelioration of hepatic steatosis and insulin resistance observed in the cSHP2-KO mice. Administration of two specific SHP2 inhibitors, SHP099 and Phps1, improved HFD-induced hepatic steatosis and insulin resistance. Our findings provide detailed insights into the role of macrophagic SHP2 in metabolic disorders. We conclude that pharmacological inhibition of SHP2 may represent a therapeutic strategy for the management of type 2 diabetes.

scholarly journals Sensing of HIV-1 by TLR8 activates human T cells and reverses latency

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Hany Zekaria Meås ◽  
Markus Haug ◽  
Marianne Sandvold Beckwith ◽  
Claire Louet ◽  
Liv Ryan ◽  
...  
Keyword(s):  
T Cells ◽  
Immune Cells ◽  
Cd4 T Cells ◽  
Vaccine Development ◽  
Inflammatory Responses ◽  
Cell Receptor ◽  
Low Grade ◽  
Activation Markers ◽  
Adaptive Immune Cells ◽  
Hiv 1

AbstractDuring HIV infection, cell-to-cell transmission results in endosomal uptake of the virus by target CD4+ T cells and potential exposure of the viral ssRNA genome to endosomal Toll-like receptors (TLRs). TLRs are instrumental in activating inflammatory responses in innate immune cells, but their function in adaptive immune cells is less well understood. Here we show that synthetic ligands of TLR8 boosted T cell receptor signaling, resulting in increased cytokine production and upregulation of surface activation markers. Adjuvant TLR8 stimulation, but not TLR7 or TLR9, further promoted T helper cell differentiation towards Th1 and Th17. In addition, we found that endosomal HIV induced cytokine secretion from CD4+ T cells in a TLR8-specific manner. TLR8 engagement also enhanced HIV-1 replication and potentiated the reversal of latency in patient-derived T cells. The adjuvant TLR8 activity in T cells can contribute to viral dissemination in the lymph node and low-grade inflammation in HIV patients. In addition, it can potentially be exploited for therapeutic targeting and vaccine development.

scholarly journals Pathophysiological Implication of Fetuin-A Glycoprotein in the Development of Metabolic Disorders: A Concise Review

2019 ◽  
Vol 8 (12) ◽  
pp. 2033 ◽  
Author(s):  
Lynda Bourebaba ◽  
Krzysztof Marycz
Keyword(s):  
Insulin Resistance ◽  
Insulin Receptor ◽  
Metabolic Disorders ◽  
Glucose Transporter ◽  
Liver Disorder ◽  
Inflammatory Factors ◽  
Human Beings ◽  
Fetuin A ◽  
Nonalcoholic Fatty Liver ◽  
Metabolism Regulation

Alpha 2-Heremans-Schmid glycoprotein, also known as fetuin-A (Fet-A), is a multifunctional plasma glycoprotein that has been identified in both animal and human beings. The protein is a hepatokine predominantly synthesized in the liver, which is considered as an important component of diverse normal and pathological processes, including bone metabolism regulation, vascular calcification, insulin resistance, and protease activity control. Epidemiological studies have already consistently demonstrated significant elevated circulating Fet-A in the course of obesity and related complications, such as type 2 diabetes mellitus, metabolic syndrome, and nonalcoholic fatty liver disorder (NAFLD). Moreover, Fet-A has been strongly correlated with many parameters related to metabolic homeostasis dysregulation, such as insulin sensitivity, glucose tolerance, circulating lipid levels (non-esterified free fatty acids and triglycerides), and circulating levels of both pro- and anti-inflammatory factors (C-reactive protein, tumor necrosis factor-α (TNF-α), and interleukin (IL)-6). Metabolic-interfering effects of Fet-A have thus been shown to highly exacerbate insulin resistance (IR) through blocking insulin-stimulated glucose transporter 4 (GLUT-4) translocation and protein kinase B (Akt) activation. Furthermore, the protein appeared to interfere with downstream phosphorylation events in insulin receptor and insulin receptor substrate signaling. The emerging importance of Fet-A for both diagnosis and therapeutics has therefore come to the attention of researchers and the pharmaceutical industry, in the prospect of developing new therapeutic strategies and diagnosis methods for metabolic disorders.

scholarly journals Reduced Immune Response to Borrelia burgdorferi in the Absence of γδ T Cells

2011 ◽  
Vol 79 (10) ◽  
pp. 3940-3946 ◽  
Author(s):  
Cuixia Shi ◽  
Bikash Sahay ◽  
Jennifer Q. Russell ◽  
Karen A. Fortner ◽  
Nicholas Hardin ◽  
...  
Keyword(s):  
Immune Response ◽  
T Cells ◽  
Borrelia Burgdorferi ◽  
Adaptive Immune Response ◽  
Γδ T Cells ◽  
Content Type ◽  
Adaptive Immune ◽  
Cytokines And Chemokines

ABSTRACTLittle is known regarding the function of γδ T cells, although they accumulate at sites of inflammation in infections and autoimmune disorders. We previously observed that γδ T cellsin vitroare activated byBorrelia burgdorferiin a TLR2-dependent manner. We now observe that the activated γδ T cells can in turn stimulate dendritic cellsin vitroto produce cytokines and chemokines that are important for the adaptive immune response. This suggested thatin vivoγδ T cells may assist in activating the adaptive immune response. We examined this possibilityin vivoand observed that γδ T cells are activated and expand in number duringBorreliainfection, and this was reduced in the absence of TLR2. Furthermore, in the absence of γδ T cells, there was a significantly blunted response of adaptive immunity, as reflected in reduced expansion of T and B cells and reduced serum levels of anti-Borreliaantibodies, cytokines, and chemokines. This paralleled a greaterBorreliaburden in γδ-deficient mice as well as more cardiac inflammation. These findings are consistent with a model of γδ T cells functioning to promote the adaptive immune response during infection.

The role of innate immune cells in obese adipose tissue inflammation and development of insulin resistance

2013 ◽  
Vol 109 (03) ◽  
pp. 399-406 ◽  
Author(s):  
Triantafyllos Chavakis ◽  
Jindrich Chmelar ◽  
Kyoung-Jin Chung
Keyword(s):  
Insulin Resistance ◽  
Adipose Tissue ◽  
Immune Cells ◽  
Cytotoxic T Cells ◽  
Innate Immune ◽  
Low Grade ◽  
Innate Immune Cells ◽  
Metabolic Complications ◽  
Adaptive Immune Cells

SummaryObesity is characterised by a chronic state of low-grade inflammation in different tissues including the vasculature. There is a causal link between adipose tissue (AT) inflammation and obesity-related metabolic complications, such as the development of insulin resistance and subsequently of type 2 diabetes. Intense efforts in the recent years have aimed at dissecting the pathophysiology of AT inflammation. The role of both innate and adaptive immune cells, such as macrophages or cytotoxic T cells in AT inflammation has been demonstrated. Besides these cells, more leukocyte subpopulations have been recently implicated in obesity, including neutrophils and eosinophils, mast cells, natural killer cells or dendritic cells. The involvement of multiple leukocyte subpopulations underlines the complexity of obesity-associated AT inflammation. In this review, we discuss the role of innate immune cells in AT inflammation, obesity and related metabolic disorders.

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