Metabolic inflammation: Connecting obesity and insulin resistance

2012 ◽  
Vol 45 (3) ◽  
pp. 242-253 ◽  
Author(s):  
Nassim Dali-Youcef ◽  
Mustapha Mecili ◽  
Roméo Ricci ◽  
Emmanuel Andrès
Keyword(s):  
Insulin Resistance ◽  
Metabolic Inflammation

scholarly journals Palmitic Acid, but Not Lauric Acid, Induces Metabolic Inflammation, Mitochondrial Fragmentation, and a Drop in Mitochondrial Membrane Potential in Human Primary Myotubes

2021 ◽  
Vol 8 ◽  
Author(s):  
Domenico Sergi ◽  
Natalie Luscombe-Marsh ◽  
Nenad Naumovski ◽  
Mahinda Abeywardena ◽  
Nathan O'Callaghan
Keyword(s):  
Insulin Resistance ◽  
Membrane Potential ◽  
Electron Transport ◽  
Mitochondrial Membrane Potential ◽  
Electron Transport Chain ◽  
Mitochondrial Membrane ◽  
Chain Complex ◽  
Mitochondrial Fragmentation ◽  
Metabolic Inflammation ◽  
Transport Chain

The chain length of saturated fatty acids may dictate their impact on inflammation and mitochondrial dysfunction, two pivotal players in the pathogenesis of insulin resistance. However, these paradigms have only been investigated in animal models and cell lines so far. Thus, the aim of this study was to compare the effect of palmitic (PA) (16:0) and lauric (LA) (12:0) acid on human primary myotubes mitochondrial health and metabolic inflammation. Human primary myotubes were challenged with either PA or LA (500 μM). After 24 h, the expression of interleukin 6 (IL-6) was assessed by quantitative polymerase chain reaction (PCR), whereas Western blot was used to quantify the abundance of the inhibitor of nuclear factor κB (IκBα), electron transport chain complex proteins and mitofusin-2 (MFN-2). Mitochondrial membrane potential and dynamics were evaluated using tetraethylbenzimidazolylcarbocyanine iodide (JC-1) and immunocytochemistry, respectively. PA, contrarily to LA, triggered an inflammatory response marked by the upregulation of IL-6 mRNA (11-fold; P < 0.01) and a decrease in IκBα (32%; P < 0.05). Furthermore, whereas PA and LA did not differently modulate the levels of mitochondrial electron transport chain complex proteins, PA induced mitochondrial fragmentation (37%; P < 0.001), decreased MFN-2 (38%; P < 0.05), and caused a drop in mitochondrial membrane potential (11%; P < 0.01) compared to control, with this effect being absent in LA-treated cells. Thus, LA, as opposed to PA, did not trigger pathogenetic mechanisms proposed to be linked with insulin resistance and therefore represents a healthier saturated fatty acid choice to potentially preserve skeletal muscle metabolic health.

Coagulation Signalling and Metabolic Disorders: Lessons Learned from Animal Models

2019 ◽  
Vol 39 (02) ◽  
pp. 164-172 ◽  
Author(s):  
Thati Madhusudhan ◽  
Wolfram Ruf
Keyword(s):  
Insulin Resistance ◽  
Clinical Studies ◽  
Metabolic Disorders ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Lessons Learned ◽  
Metabolic Reprogramming ◽  
Metabolic Adaptation ◽  
Metabolic Inflammation ◽  
Cardiometabolic Disorders

AbstractNutrient excess in obesity drives metabolic reprogramming in multiple tissues involving extensive interorgan and intercellular crosstalk. Experimental and clinical studies show that prolonged nutrient excess often compromises metabolic adaptation propagating proobesogenic and proinflammatory responses. Chronic inflammation further promotes insulin resistance and associated comorbidities. Obesity and type 2 diabetes are characterized by a hypercoagulable state and clinical studies show a strong correlation of markers of coagulation activation in metabolic disorders. Coagulation protease-dependent signalling via protease-activated receptors is intimately associated with inflammation. The experimental evidence supports roles of tissue factor and G protein coupled protease-activated receptor-2 signalling in the regulation of insulin resistance and metabolic inflammation in diet-induced obesity. Likewise, increases in plasminogen activator inhibitor-1 levels and fibrin-driven inflammation promote insulin resistance in obesity. Additionally, impaired thrombomodulin-dependent protein C activation is mechanistically linked to diabetic kidney disease. Given the increased usage of direct oral anticoagulants, understanding the role of specific coagulation proteases in regulation of metabolic inflammation is highly relevant and might provide insights into the design of novel treatment regimens for patients suffering from thromboinflammatory and cardiometabolic disorders.

scholarly journals Role of T Lymphocytes in Type 2 Diabetes and Diabetes-Associated Inflammation

2017 ◽  
Vol 2017 ◽  
pp. 1-6 ◽  
Author(s):  
Chang Xia ◽  
Xiaoquan Rao ◽  
Jixin Zhong
Keyword(s):  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
T Cells ◽  
Immune System ◽  
Critical Role ◽  
Adaptive Immune System ◽  
Metabolic Inflammation ◽  
Adaptive Immune

Although a critical role of adaptive immune system has been confirmed in driving local and systemic inflammation in type 2 diabetes and promoting insulin resistance, the underlying mechanism is not completely understood. Inflammatory regulation has been focused on innate immunity especially macrophage for a long time, while increasing evidence suggests T cells are crucial for the development of metabolic inflammation and insulin resistance since 2009. There was growing evidence supporting the critical implication of T cells in the pathogenesis of type 2 diabetes. We will discuss the available effect of T cells subsets in adaptive immune system associated with the procession of T2DM, which may unveil several potential strategies that could provide successful therapies in the future.

scholarly journals Myeloid cell TRAF3 promotes metabolic inflammation, insulin resistance, and hepatic steatosis in obesity

2015 ◽  
Vol 308 (6) ◽  
pp. E460-E469 ◽  
Author(s):  
Zheng Chen ◽  
Hong Shen ◽  
Chengxin Sun ◽  
Lei Yin ◽  
Fei Tang ◽  
...  
Keyword(s):  
Metabolic Disease ◽  
Insulin Resistance ◽  
Adipose Tissue ◽  
Disease Progression ◽  
Hepatic Steatosis ◽  
Proinflammatory Cytokines ◽  
Myeloid Cell ◽  
Metabolic Inflammation ◽  
Molecular Patterns ◽  
Specific Deletion

Myeloid cells, particularly macrophages, mediate metabolic inflammation, thus promoting insulin resistance and metabolic disease progression in obesity. Numerous cytokines, toxic metabolites, damage-associated molecular patterns, and pathogen-associated molecular patterns are involved in activating macrophages via their cognate receptors in obesity. TRAF3 (TNF receptor-associated factor 3) is a common signaling molecule for these ligands/receptors and negatively regulates the proinflammatory NF-κB and MAPK pathways, but its metabolic activity is unknown. We here show that myeloid cell TRAF3 is required for metabolic inflammation and metabolic disease progression in obesity. Myeloid cell-specific deletion of TRAF3 significantly attenuated insulin resistance, hyperglycemia, hyperinsulinemia, glucose intolerance, and hepatic steatosis in mice with either genetic ( ob/ob) or high-fat diet (HFD)-induced obesity. Myeloid cell-specific deletion of TRAF3 had the opposite effects on metabolic inflammation between obese and lean mice. It decreased the expression of proinflammatory cytokines in the liver and adipose tissue of obese mice and largely prevented HFD-induced inflammation in these metabolic tissues; by contrast, in lean mice, it increased the expression of proinflammatory cytokines in the liver and adipose tissue. These data suggest that, in obesity progression, myeloid TRAF3 functionally switches its activity from anti-inflammatory to proinflammatory modes, thereby coupling overnutrition to metabolic inflammation, insulin resistance, and metabolic disease.

scholarly journals Etiopathogenetic parallels and unresolved issues of pathogenesis of comorbidity COPD and metabolic syndrome (review)

2020 ◽  
Vol 17 (3) ◽  
pp. 292-298
Author(s):  
Olga V. Voronkova ◽  
Tatyana V. Saprina ◽  
Ekaterina B. Bukreeva ◽  
Anastasia P. Zima
Keyword(s):  
Risk Factors ◽  
Insulin Resistance ◽  
Metabolic Syndrome ◽  
Chronic Obstructive ◽  
Obstructive Pulmonary Disease ◽  
Innate And Adaptive Immunity ◽  
Future Studies ◽  
Metabolic Inflammation ◽  
Pathogenetic Therapy ◽  
Main Components

The review analyzes the etiological and pathogenetic factors (including immunopathogenesis factors) of chronic obstructive pulmonary disease (COPD) and metabolic syndrome (MS), cites data on clinical and pathogenetic characteristics of combined pathology, emphasizes the commonality of risk factors and individual links of pathogenesis in syntropy.The clinical and pathogenetic features of the comorbidity of COPD and MS are closely related to the severity of chronic “metabolic” inflammation induced by elements of adipose tissue. Functional and biochemical disorders recorded in metabolic syndrome (insulin resistance, hyperglycemia, dyslipidemia) are considered as factors contributing to dysfunction of the components of innate and adaptive immunity.The review formulates a number of unresolved issues of the pathogenesis of comorbid pathology, the study of which is necessary to search for the mutual aggravating effect of COPD and MS mechanisms. In view of the clinical and laboratory metabolic syndrome equivalents variety, the authors emphasize the relevance of future studies of the pathogenetic features of chronic inflammation associated with the comorbidity of the main components of metabolic syndrome and COPD, to develop effective methods of prevention and pathogenetic therapy of comorbid pathology.

scholarly journals Myeloid Krüppel-like factor 2 is a critical regulator of metabolic inflammation

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
David R. Sweet ◽  
Neelakantan T. Vasudevan ◽  
Liyan Fan ◽  
Chloe E. Booth ◽  
Komal S. Keerthy ◽  
...  
Keyword(s):  
Metabolic Disease ◽  
Insulin Resistance ◽  
Bone Marrow ◽  
High Fat Diet ◽  
Marrow Transplant ◽  
Metabolic Dysfunction ◽  
Disease Phenotype ◽  
High Fat ◽  
Substantial Evidence ◽  
Metabolic Inflammation

AbstractSubstantial evidence implicates crosstalk between metabolic tissues and the immune system in the inception and progression of obesity. However, molecular regulators that orchestrate metaflammation both centrally and peripherally remains incompletely understood. Here, we identify myeloid Krüppel-like factor 2 (KLF2) as an essential regulator of obesity and its sequelae. In mice and humans, consumption of a fatty diet downregulates myeloid KLF2 levels. Under basal conditions, myeloid-specific KLF2 knockout mice (K2KO) exhibit increased feeding and weight gain. High-fat diet (HFD) feeding further exacerbates the K2KO metabolic disease phenotype. Mechanistically, loss of myeloid KLF2 increases metaflammation in peripheral and central tissues. A combination of pair-feeding, bone marrow-transplant, and microglial ablation implicate central and peripheral contributions to K2KO-induced metabolic dysfunction observed. Finally, overexpression of myeloid KLF2 protects mice from HFD-induced obesity and insulin resistance. Together, these data establish myeloid KLF2 as a nodal regulator of central and peripheral metabolic inflammation in homeostasis and disease.

scholarly journals Postbiotics for NOD2 require nonhematopoietic RIPK2 to improve blood glucose and metabolic inflammation in mice

2020 ◽  
Vol 318 (4) ◽  
pp. E579-E585 ◽  
Author(s):  
Joseph F. Cavallari ◽  
Nicole G. Barra ◽  
Kevin P. Foley ◽  
Amanda Lee ◽  
Brittany M. Duggan ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Blood Glucose ◽  
Metabolic Diseases ◽  
Hematopoietic Cells ◽  
Tolerance Test ◽  
Whole Body ◽  
Glucose Lowering ◽  
Endotoxin Challenge ◽  
Metabolic Inflammation ◽  
Anti Inflammatory

Defining the host receptors and metabolic consequences of bacterial components can help explain how the microbiome influences metabolic diseases. Bacterial peptidoglycans that activate nucleotide-binding oligomerization domain-containing (NOD)1 worsen glucose control, whereas NOD2 activation improves glycemia. Receptor-interacting serine/threonine-protein kinase 2 (RIPK2) is required for innate immunity instigated by NOD1 and NOD2. The role of RIPK2 in the divergent effects of NOD1 versus NOD2 on blood glucose was unknown. We found that whole body deletion of RIPK2 negated all effects of NOD1 or NOD2 activation on blood glucose during an acute, low level endotoxin challenge in mice. It was known that NOD1 in hematopoietic cells participates in insulin resistance and metabolic inflammation in obese mice. It was unknown if RIPK2 in hematopoietic cells is required for the glucose-lowering and anti-inflammatory effects of NOD2 activation. We hypothesized that RIPK2 in nonhematopoietic cells dictated the glycemic effects of NOD2 activation. We found that whole body deletion of RIPK2 prevented the glucose-lowering effects of repeated NOD2 activation that were evident during a glucose tolerance test (GTT) in high-fat diet (HFD)-fed wild-type (WT) mice. NOD2 activation lowered glucose during a GTT and lowered adipose tissue inflammation in mice with RIPK2 deleted in hematopoietic cells. We conclude that RIPK2 in nonhematopoietic cells mediates the glucose lowering and anti-inflammatory effects of NOD2-activating postbiotics. We propose a model where lipopolysaccharides and NOD1 ligands synergize in hematopoietic cells to promote insulin resistance but NOD2 activation in nonhematopoietic cells promotes RIPK2-dependent immune tolerance and lowering of inflammation and insulin resistance.

scholarly journals TLR4/AP-1-Targeted Anti-Inflammatory Intervention Attenuates Insulin Sensitivity and Liver Steatosis

2020 ◽  
Vol 2020 ◽  
pp. 1-11 ◽  
Author(s):  
Xiang Hu ◽  
Jing Zhou ◽  
Sha-sha Song ◽  
Wen Kong ◽  
Yan-Chuan Shi ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Insulin Sensitivity ◽  
Signaling Pathway ◽  
High Fat Diet ◽  
Macrophage Polarization ◽  
Liver Steatosis ◽  
Lipid Deposition ◽  
Sirna Transfection ◽  
High Fat ◽  
Metabolic Inflammation

Insulin resistance has been shown to be the common pathogenesis of many metabolic diseases. Metainflammation is one of the important characteristics of insulin resistance. Macrophage polarization mediates the production and development of metainflammation. Toll-like receptor 4 (TLR4) mediates macrophage activity and is probably the intersection of immunity and metabolism, but the detailed mechanism is probably not fully understood. Activated protein 1 (AP1) signaling pathway is very important in macrophage activation-mediated inflammation. However, it is unclear whether AP1 signaling pathway mediates metabolic inflammation in the liver. We aimed to investigate the effects of macrophage TLR4-AP1 signaling pathway on hepatocyte metabolic inflammation, insulin sensitivity, and lipid deposition, as well as to explore the potential of TLR4-AP1 as new intervention targets of insulin resistance and liver steatosis. TLR4 and AP1 were silenced in the RAW264.7 cells by lentiviral siRNA transfection. In vivo transduction of lentivirus was administered in mice fed with high-fat diet. Insulin sensitivity and inflammation were evaluated in the treated cells or animals. Our results indicated that TLR4/AP-1 siRNA transfection alleviated high-fat diet-induced systemic and hepatic inflammation, obesity, and insulin resistance in mice. Additionally, TLR4/AP-1 siRNA transfection mitigated palmitic acid- (PA-) induced inflammation in RAW264.7 cells and metabolic abnormalities in cocultured AML hepatocytes. Herein, we propose that TLR4-AP1 signaling pathway activation plays a crucial role in high fat- or PA-induced metabolic inflammation and insulin resistance in hepatocytes. Intervention of the TLR4 expression regulates macrophage polarization and metabolic inflammation and further alleviates insulin resistance and lipid deposition in hepatocytes.

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