scholarly journals Regulation of adipogenic differentiation and adipose tissue inflammation by interferon regulatory factor 3

2021 ◽  
Author(s):  
Peng Tang ◽  
Sam Virtue ◽  
Jian Yi Gerald Goie ◽  
Chin Wen Png ◽  
Jing Guo ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Adipose Tissue ◽  
Metabolic Diseases ◽  
Adipogenic Differentiation ◽  
Interferon Regulatory Factor ◽  
Therapeutic Interventions ◽  
Regulatory Factor ◽  
Primary Defect ◽  
Interferon Regulatory Factor 3

AbstractDysfunction of adipocytes and adipose tissue is a primary defect in obesity and obesity-associated metabolic diseases. Interferon regulatory factor 3 (IRF3) has been implicated in adipogenesis. However, the role of IRF3 in obesity and obesity-associated disorders remains unclear. Here, we show that IRF3 expression in human adipose tissues is positively associated with insulin sensitivity and negatively associated with type 2 diabetes. In mouse pre-adipocytes, deficiency of IRF3 results in increased expression of PPARγ and PPARγ-mediated adipogenic genes, leading to increased adipogenesis and altered adipocyte functionality. The IRF3 knockout (KO) mice develop obesity, insulin resistance, glucose intolerance, and eventually type 2 diabetes with aging, which is associated with the development of white adipose tissue (WAT) inflammation. Increased macrophage accumulation with M1 phenotype which is due to the loss of IFNβ-mediated IL-10 expression is observed in WAT of the KO mice compared to that in wild-type mice. Bone-marrow reconstitution experiments demonstrate that the nonhematopoietic cells are the primary contributors to the development of obesity and both hematopoietic and nonhematopoietic cells contribute to the development of obesity-related complications in IRF3 KO mice. This study demonstrates that IRF3 regulates the biology of multiple cell types including adipocytes and macrophages to prevent the development of obesity and obesity-related complications and hence, could be a potential target for therapeutic interventions for the prevention and treatment of obesity-associated metabolic disorders.

scholarly journals The Construction and Analysis of the Aberrant lncRNA-miRNA-mRNA Network in Adipose Tissue from Type 2 Diabetes Individuals with Obesity

2020 ◽  
Vol 2020 ◽  
pp. 1-14 ◽  
Author(s):  
Wei Hu ◽  
Yuanlin Ding ◽  
Shu Wang ◽  
Lin Xu ◽  
Haibing Yu
Keyword(s):  
Type 2 Diabetes ◽  
Adipose Tissue ◽  
Metabolic Diseases ◽  
Therapeutic Targets ◽  
Predictive Biomarkers ◽  
Biological Pathways ◽  
Differentially Expressed ◽  
Public Health Issue ◽  
Cerna Network

Background. The prevalence of obesity and type 2 diabetes mellitus (T2DM) has become the most serious global public health issue. In recent years, there has been increasing attention to the role of long noncoding RNAs (lncRNAs) in the occurrence and development of obesity and T2DM. The aim of this work was to find new lncRNAs as potential predictive biomarkers or therapeutic targets for obesity and T2DM. Methods. In this study, we identified significant differentially expressed mRNAs (DEmRNAs) and differentially expressed lncRNAs (DElncRNAs) between adipose tissue of individuals with obesity and T2DM and normal adipose tissue (absolute log2FC≥1 and FDR<0.05). Then, the lncRNA-miRNA interactions predicted by miRcode were further screened with a threshold of MIC>0.2. Simultaneously, the mRNA-miRNA interactions were explored by miRWalk 2.0. Finally, a ceRNA network consisting of lncRNAs, miRNAs, and mRNAs was established by integrating lncRNA-miRNA interactions and mRNA-miRNA interactions. Results. Upon comparing adipose tissue from individuals with obesity and T2DM and normal adipose tissues, 364 significant DEmRNAs, including 140 upregulated and 224 downregulated mRNAs, were identified in GSE104674; in addition, 231 significant DEmRNAs, including 146 upregulated and 85 downregulated mRNAs, were identified in GSE133099. GO and KEGG analyses have shown that downregulated DEmRNAs in GSE104674 and GSE133099 were associated with obesity- and T2DM-related biological pathways, such as lipid metabolism, AMPK signaling, and insulin resistance. Furthermore, 28 significant DElncRNAs, including 14 upregulated and 14 downregulated lncRNAs, were found. Based on the predicted lncRNA-miRNA and mRNA-miRNA relationships, we constructed a competitive endogenous RNA (ceRNA) network, including five lncRNAs, ten miRNAs, and 15 mRNAs. KEGG-GSEA analysis revealed that four lncRNAs (FLG-AS1, SNAI3-AS1, AC008147.0, and LINC02015) in the ceRNA network were related to the biological pathways of metabolic diseases. Conclusions. Through ceRNA network analysis, our study identified four new lncRNAs that may be used as potential biomarkers and therapeutic targets of obesity and T2DM, thus laying a foundation for future clinical studies.

Modulation of energy balance by fibroblast growth factor 21

2016 ◽  
Vol 30 (1) ◽  
Author(s):  
Daniel Cuevas-Ramos ◽  
Carlos A. Aguilar-Salinas
Keyword(s):  
Type 2 Diabetes ◽  
Adipose Tissue ◽  
Energy Balance ◽  
Energy Expenditure ◽  
Metabolic Diseases ◽  
Fibroblast Growth Factor 21 ◽  
Fibroblast Growth ◽  
The Metabolic Syndrome ◽  
Brown Adipose

AbstractFibroblast growth factors (FGFs) are a superfamily of 22 proteins related to cell proliferation and tissue repair after injury. A subgroup of three proteins, FGF19, FGF21, and FGF23, are major endocrine mediators. These three FGFs have low affinity to heparin sulfate during receptor binding; in contrast they have a strong interaction with the cofactor Klotho/β-Klotho. FGF21 has received particular attention because of its key role in carbohydrate, lipids, and energy balance regulation. FGF21 improves glucose and lipids metabolism as well as increasing energy expenditure in animal models and humans. Conditions that induce human physical stress such as exercise, lactation, obesity, insulin resistance, and type 2 diabetes influence FGF21 circulating levels. FGF21 also has an anti-oxidant function in human metabolic diseases which contribute to understanding the FGF21 compensatory increment in obesity, the metabolic syndrome, and type 2 diabetes. Interestingly, energy expenditure and weight loss is induced by FGF21. The mechanism involved is through “browning” of white adipose tissue, increasing brown adipose tissue activity and heat production. Therefore, clinical evaluation of therapeutic action of exogenous FGF21 administration is warranted, particularly to treat diabetes and obesity.

Diet, obesity and diabetes: a current update

2006 ◽  
Vol 112 (2) ◽  
pp. 93-111 ◽  
Author(s):  
Celia G. Walker ◽  
M. Gulrez Zariwala ◽  
Mark J. Holness ◽  
Mary C. SUGDEN
Keyword(s):  
Type 2 Diabetes ◽  
Adipose Tissue ◽  
Energy Balance ◽  
Whole Body ◽  
Primary Defect ◽  
Obesity And Diabetes ◽  
Tissue Factors ◽  
Metabolic Conditions ◽  
The Impact

The prevalence of obesity has been increasing at a rapid rate over the last few decades. Although the primary defect can be attributed to an imbalance of energy intake over energy expenditure, the regulation of energy balance is now recognized to be complex. Adipose-tissue factors play a central role in the control of energy balance and whole-body fuel homoeostasis. The regulation of adipose-tissue function, in particular its secretion of adipokines, is impaired by increases in adipose mass associated with obesity, and with the development of insulin resistance and Type 2 diabetes. This review analyses adipose-regulated energy input and expenditure, together with the impact of dietary macronutrient composition on energy balance in relation to susceptibility to the development of obesity and Type 2 diabetes, and how these metabolic conditions may be exacerbated by the consequences of abnormal adipose function. By gaining a greater understanding of how energy balance is controlled in normal, and in obese and diabetic states, a more practical approach can be employed to prevent and better treat obesity and metabolic disorders.

scholarly journals Effects of fitness qigong and tai chi on middle-aged and elderly patients with type 2 diabetes mellitus

PLoS ONE ◽  
2020 ◽  
Vol 15 (12) ◽  
pp. e0243989
Author(s):  
Xiaoyuan Li ◽  
Hongyu Si ◽  
Yamin Chen ◽  
Shouhao Li ◽  
Ningning Yin ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Tai Chi ◽  
Metabolic Diseases ◽  
Therapeutic Interventions ◽  
Control Group ◽  
Middle Aged ◽  
Clinical Trial Registry

Currently, qigong and tai chi exercises are the two most common preventive as well as therapeutic interventions for chronic metabolic diseases such as type 2 diabetes mellitus (T2DM). However, the quantitative evaluation of these interventions is limited. This study aimed to evaluate the therapeutic efficacy of qigong and tai chi intervention in middle-aged and older adults with T2DM. The study included 103 eligible participants, who were randomized to participate for 12 weeks, in one of the following intervention groups for the treatment of T2DM: fitness qigong, tai chi, and control group. Three biochemical measures, including fasting plasma glucose (FPG), glycated hemoglobin (HbA1C), and C-peptide (C-P) levels, assessed at baseline and 12 weeks, served as the primary outcome measures. During the training process, 16 of the 103 participants dropped out. After the 12-week intervention, there were significant influences on HbA1C (F2,83 = 4.88, p = 0.010) and C-P levels (F2,83 = 3.64, p = 0.031). Moreover, significant reduction in C-P levels was observed after 12-week tai chi practice (p = 0.004). Furthermore, there was a significant negative correlation between the duration of T2DM and the relative changes in FPG levels after qigong intervention, and the relative changes in HbA1C levels were positively correlated with waist-to-height ratio after tai chi practice. Our study suggests that targeted qigong exercise might have a better interventional effect on patients with a longer duration of T2DM, while tai chi might be risky for people with central obesity. Trial registration: This trial was registered in Chinese Clinical Trial Registry. The registration number is ChiCTR180020069. The public title is “Health-care qigong · study for the prescription of chronic diabetes intervention.”

Interferon regulatory factor 7 deficiency prevents diet-induced obesity and insulin resistance

2013 ◽  
Vol 305 (4) ◽  
pp. E485-E495 ◽  
Author(s):  
Xin-An Wang ◽  
Ran Zhang ◽  
Shumin Zhang ◽  
Shan Deng ◽  
Dingsheng Jiang ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Insulin Sensitivity ◽  
Energy Metabolism ◽  
Interferon Regulatory Factor ◽  
Type I ◽  
Regulatory Factor ◽  
Multiple Organs ◽  
Interferon Regulatory Factor 7

Obesity-related inflammation has been implicated in the pathogenesis of insulin resistance and type 2 diabetes. In this study, we addressed the potential role of interferon regulatory factor 7 (IRF7), a master regulator of type I interferon-dependent immune responses, in the regulation of energy metabolism. The expression levels of IRF7 were increased in white adipose tissue, liver tissue, and gastrocnemius muscle of both diet-induced obese mice and ob/ ob mice compared with their lean counterparts. After feeding a high-fat diet (HFD) for 24 wk, IRF7 knockout (KO) mice showed less weight gain and adiposity than wild-type controls. KO of IRF7 improved glucose and lipid homeostasis and insulin sensitivity. Additionally, KO of IRF7 ameliorated diet-induced hepatic steatosis. Next, we assessed the inflammatory state of the IRF7 KO mice on the HFD. These mice showed less macrophage infiltration into multiple organs and were protected from local and systemic inflammation. This study demonstrates a role for IRF7 in diet-induced alterations in energy metabolism and insulin sensitivity. Our results also suggest that IRF7 is involved in the etiology of metabolic abnormalities, which suggests a new strategy for treating obesity and type 2 diabetes.

scholarly journals Toll-Like Receptor Ligands Cause Proinflammatory and Prodiabetic Activation of Adipocytes via Phosphorylation of Extracellular Signal-Regulated Kinase and c-Jun N-Terminal Kinase But Not Interferon Regulatory Factor-3

Endocrinology ◽  
2010 ◽  
Vol 151 (3) ◽  
pp. 1097-1108 ◽  
Author(s):  
Andrea Kopp ◽  
Christa Buechler ◽  
Margarita Bala ◽  
Markus Neumeier ◽  
Juergen Schölmerich ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Interferon Regulatory Factor ◽  
Mitogen Activated Protein Kinase ◽  
Human Adipocytes ◽  
Toll Like Receptor ◽  
Regulatory Factor ◽  
Interferon Regulatory Factor 3 ◽  
Monocyte Chemoattractant Protein 1 ◽  
Extracellular Signal Regulated Kinase ◽  
Extracellular Signal

Here, we aim to investigate the mechanisms of Toll-like receptor (TLR)-induced prodiabetic and proinflammatory activation of adipocytes and to detect differences in the responsiveness of TLRs to their respective ligands between adipocytes isolated from inflamed vs. noninflamed adipose tissue. Experiments using specific ligands for all known TLRs were performed in murine 3T3-L1 adipocytes and in human adipocytes isolated from noninflamed and inflamed adipose tissue. IL-6 and monocyte chemoattractant protein-1 (MCP-1) release were measured by ELISA. The expression of the signal transduction proteins phospho-extracellular signal-regulated kinase (P-Erk), P-c-Jun N-terminal kinase (JNK), and P-interferon regulatory factor-3 was investigated by Western blot analysis. Additionally, functional inhibitors of MAPK kinase-1/-2 and JNK-1/-2 were used in the stimulation experiments. Activation of TRL4 by lipopolysaccharide (LPS) and TLR1/2 by Pam3Cys up-regulates IL-6 and MCP-1 release in adipocytes via specific activation of Erk. Stimulation of adipocytes by macrophage activating lipopeptide-2 (MALP-2) induces MCP-1 but has no effect on IL-6 release. This stimulatory effect on MCP-1 release is antagonized by inhibition of both mitogen-activated protein kinase-1/-2 and JNK-1/-2. Phosphorylation of Erk and JNK is up-regulated after stimulation by MALP-2. In human adipocytes isolated from noninflamed adipose tissue, LPS and Pam3Cys, but not MALP-2, are potent inducers of IL-6 and MCP-1. MALP-2 is able to induce IL-6 and MCP-1 release in adipocytes isolated from inflamed adipose tissue, whereas these adipocytes lost their ability to respond to LPS. The present results point to a role of the adipose tissue in innate immunity. TLR-ligand-induced proinflammatory and prodiabetic activation of adipocytes might couple visceral adipose tissue dysfunction with insulin resistance and type 2 diabetes mellitus.

scholarly journals Adipose tissue in health and disease

Open Biology ◽  
2020 ◽  
Vol 10 (12) ◽  
pp. 200291
Author(s):  
Innocence Harvey ◽  
Anik Boudreau ◽  
Jacqueline M. Stephens
Keyword(s):  
Type 2 Diabetes ◽  
Metabolic Syndrome ◽  
Adipose Tissue ◽  
Metabolic Diseases ◽  
Metabolic Dysfunction ◽  
Fat Tissue ◽  
Disease States ◽  
Rigorous Research ◽  
Health And Disease

Adipose, or fat, tissue (AT) was once considered an inert tissue that primarily existed to store lipids, and was not historically recognized as an important organ in the regulation and maintenance of health. With the rise of obesity and more rigorous research, AT is now recognized as a highly complex metabolic organ involved in a host of important physiological functions, including glucose homeostasis and a multitude of endocrine capabilities. AT dysfunction has been implicated in several disease states, most notably obesity, metabolic syndrome and type 2 diabetes. The study of AT has provided useful insight in developing strategies to combat these highly prevalent metabolic diseases. This review highlights the major functions of adipose tissue and the consequences that can occur when disruption of these functions leads to systemic metabolic dysfunction.

scholarly journals Is type 2 diabetes an adiposity-based metabolic disease? From the origin of insulin resistance to the concept of dysfunctional adipose tissue

2021 ◽  
Author(s):  
Paolo Sbraccia ◽  
Monica D’Adamo ◽  
Valeria Guglielmi
Keyword(s):  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Adipose Tissue ◽  
Association Studies ◽  
Published Data ◽  
Past Century ◽  
Genome Wide Association Studies ◽  
Primary Defect ◽  
Level Of Evidence

AbstractIn the last decades of the past century, a remarkable amount of research efforts, money and hopes was generated to unveil the basis of insulin resistance that was believed to be the primary etiological factor in the development of type 2 diabetes. From the Reaven’s insulin resistance syndrome to the DeFronzo’s triumvirate (skeletal muscle, liver and beta-cell) and to Kahn’s discovery (among many others) of insulin receptor downregulation and autophosphorylation, an enthusiastic age of metabolic in vivo and in vitro research took place, making the promise of a resolutory ending. However, from many published data (those of insulin receptoropathies and lipodystrophies, the genome-wide association studies results, the data on reversibility of type 2 diabetes after bariatric surgery or very-low-calorie diets, and many others) it appears that insulin resistance is not a primary defect but it develops secondarily to increased fat mass. In particular, it develops from a mismatch between the surplus caloric intake and the storage capacity of adipose tissue. On this basis, we propose to change the today’s definition of type 2 diabetes in adiposity-based diabetes.Level of Evidence as a narrative review a vast array of studies have been included in the analysis, ranging from properly designed randomized controlled trials to case studies; however, the overall conclusion may be regarded as level IV.

scholarly journals Emerging Roles for the INK4a/ARF (CDKN2A) Locus in Adipose Tissue: Implications for Obesity and Type 2 Diabetes

Biomolecules ◽  
2020 ◽  
Vol 10 (9) ◽  
pp. 1350
Author(s):  
Yasmina Kahoul ◽  
Frédérik Oger ◽  
Jessica Montaigne ◽  
Philippe Froguel ◽  
Christophe Breton ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Adipose Tissue ◽  
Energy Homeostasis ◽  
Metabolic Diseases ◽  
Association Studies ◽  
Cardiovascular Complications ◽  
Genome Wide Association Studies ◽  
Nucleotide Polymorphisms ◽  
Cdkn2a Locus

Besides its role as a cell cycle and proliferation regulator, the INK4a/ARF (CDKN2A) locus and its associated pathways are thought to play additional functions in the control of energy homeostasis. Genome-wide association studies in humans and rodents have revealed that single nucleotide polymorphisms in this locus are risk factors for obesity and related metabolic diseases including cardiovascular complications and type-2 diabetes (T2D). Recent studies showed that both p16INK4a-CDK4-E2F1/pRB and p19ARF-P53 (p14ARF in humans) related pathways regulate adipose tissue (AT) physiology and adipocyte functions such as lipid storage, inflammation, oxidative activity, and cellular plasticity (browning). Targeting these metabolic pathways in AT emerged as a new putative therapy to alleviate the effects of obesity and prevent T2D. This review aims to provide an overview of the literature linking the INK4a/ARF locus with AT functions, focusing on its mechanisms of action in the regulation of energy homeostasis.

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