scholarly journals Fetuin-A regulates adipose tissue macrophage content and activation in insulin resistant mice through MCP-1 and iNOS: Involvement of IFNγ-JAK2-STAT1 pathway

2021 ◽  
Author(s):  
Dipanjan Chattopadhyay ◽  
Snehasis Das ◽  
Suktara Guria ◽  
Soumyadeep Basu ◽  
Sutapa Mukherjee
Keyword(s):  
Adipose Tissue ◽  
Macrophage Polarization ◽  
Interferon Γ ◽  
Adipose Tissue Inflammation ◽  
Fetuin A ◽  
Monocyte Chemoattractant Protein 1 ◽  
Tissue Inflammation ◽  
Tissue Macrophage ◽  
Adipose Tissue Macrophage ◽  
Anti Inflammatory

In the context of obesity-induced adipose tissue inflammation, migration of macrophages and their polarization from predominantly anti-inflammatory to proinflammatory subtype is considered a pivotal event in the loss of adipose insulin sensitivity. Two major chemoattractants, monocyte chemoattractant protein-1 (MCP-1) and Fetuin A (FetA), have been reported to stimulate macrophage migration into inflamed adipose tissue instigating inflammation. Moreover, FetA could notably modulate macrophage polarization, yet the mechanism(s) is unknown. The present study was undertaken to elucidate the mechanistic pathway involved in the actions of FetA and MCP-1 in obese adipose tissue. We found that FetA knockdown in high fat diet (HFD) fed mice could significantly subdue the augmented MCP-1 expression and reduce adipose tissue macrophage (ATM) content thereby indicating that MCP-1 is being regulated by FetA. Additionally, knockdown of FetA in HFD mice impeded the expression of inducible nitric oxide synthase (iNOS) reverting macrophage activation from mostly proinflammatory to anti-inflammatory state. It was observed that the stimulating effect of FetA on MCP-1 and iNOS was mediated through interferon γ (IFNγ) induced activation of JAK2-STAT1-NOX4 pathway. Furthermore, we detected that the enhanced IFNγ expression was accounted by the stimulatory effect of FetA upon the activities of both cJun and JNK. Taken together, our findings revealed that obesity-induced FetA acts as a master upstream regulator of adipose tissue inflammation by regulating MCP-1 and iNOS expression through JNK-cJun-IFNγ-JAK2-STAT1 signaling pathway. This study opened a new horizon in understanding the regulation of ATM content and activation in conditions of obesity-induced insulin resistance.

PS15 - 77. GPNMB is induced by adipose tissue macrophage during obesity and contributes to adipose tissue inflammation

2011 ◽  
Vol 9 (3) ◽  
pp. 143-143
Author(s):  
Tanit Lizama ◽  
Jan Aten ◽  
Roelof Ottenhof ◽  
Cindy van Roomen ◽  
Nike Claessen ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Adipose Tissue Inflammation ◽  
Tissue Inflammation ◽  
Tissue Macrophage ◽  
Adipose Tissue Macrophage

scholarly journals Tart Cherry Reduces Inflammation in Adipose Tissue of Zucker Fatty Rats and Cultured 3T3-L1 Adipocytes

Nutrients ◽  
2018 ◽  
Vol 10 (11) ◽  
pp. 1576 ◽  
Author(s):  
Shasika Jayarathne ◽  
April Stull ◽  
Alexandra Miranda ◽  
Shane Scoggin ◽  
Kate Claycombe-Larson ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Fatty Acid Synthase ◽  
Related Factor ◽  
Mrna Levels ◽  
Nuclear Factor ◽  
Adipose Tissue Inflammation ◽  
Tart Cherry ◽  
Tissue Inflammation ◽  
Anti Inflammatory

Obesity increases adipose tissue inflammation and secretion of pro-inflammatory adipokines, which have systemic effects on the organism’s health status. Our objective was to dissect mechanisms of anti-inflammatory effects of tart cherry (TC) in adipose tissue of Zucker fatty rats, and cultured 3T3-L1 adipocytes. Rats were fed either a control diet, or 4% TC powder diets for eight weeks. Body and epididymal fat pad weights were not significantly different between control and TC groups. However, rats fed the TC diet had significantly reduced adipose tissue inflammation (p < 0.05), as determined by reduced mRNA levels of pro-inflammatory markers including interleukin-6 (IL-6), tumor necrosis factor alpha (TNFα), interleukin-1beta (IL-1β), monocyte chemoattractant protein 1 (MCP-1), inducible nitric oxide synthase (iNOS), and CD-11b, and increased mRNA levels of type-1 arginase (Arg-1) anti-inflammatory marker. Consistent with these in vivo results, TC significantly decreased expression of IL-6 mRNA and protein levels in lipopolysaccharide (LPS) stimulated adipocytes compared to those stimulated with LPS, but no TC. Moreover, both in vivo (rat adipose tissue) and in vitro (3T3-L1 adipocytes), phosphorylation of p65-NF-κB subunit was significantly reduced by TC. Additionally, TC decreased mRNA expression of fatty acid synthase (FASN), and increased expression of peroxisome proliferator-activated receptor alpha (PPARα), master regulator of lipid oxidation, and anti-oxidant markers nuclear factor erythroid-derived 2-related factor (NRFs) in both models. In conclusion, our findings indicate that TC downregulates inflammation in part via the nuclear factor kappa B (NF-κB) pathway in adipose tissue. Thus, TC may serve as a potential intervention to reduce obesity-associated inflammation.

scholarly journals Life-span Extension Drug Interventions Affect Adipose Tissue Inflammation in Aging

2019 ◽  
Vol 75 (1) ◽  
pp. 89-98 ◽  
Author(s):  
Theresa Mau ◽  
Martin O’Brien ◽  
Amiya K Ghosh ◽  
Richard A Miller ◽  
Raymond Yung
Keyword(s):  
Adipose Tissue ◽  
Life Span ◽  
Adipose Tissue Inflammation ◽  
Life Span Extension ◽  
Testing Program ◽  
Tissue Inflammation ◽  
Tissue Macrophage ◽  
Organ Specific ◽  
Inflammatory Processes ◽  
Drug Interventions

Abstract The National Institute on Aging (NIA)-sponsored Interventions Testing Program (ITP) has identified a number of dietary drug interventions that significantly extend life span, including rapamycin, acarbose, and 17-α estradiol. However, these drugs have diverse downstream targets, and their effects on age-associated organ-specific changes are unclear (Nadon NL, Strong R, Miller RA, Harrison DE. NIA Interventions Testing Program: investigating putative aging intervention agents in a genetically heterogeneous mouse model. EBioMedicine. 2017;21:3–4. doi:10.1016/j.ebiom.2016.11.038). Potential mechanisms by which these drugs extend life could be through their effect on inflammatory processes often noted in tissues of aging mice and humans. Our study focuses on the effects of three drugs in the ITP on inflammation in gonadal white adipose tissue (gWAT) of HET3 mice—including adiposity, adipose tissue macrophage (ATM) M1/M2 polarization, markers of cellular senescence, and endoplasmic reticulum stress. We found that rapamycin led to a 56% increase of CD45+ leukocytes in gWAT, where the majority of these are ATMs. Interestingly, rapamycin led to a 217% and 106% increase of M1 (CD45+CD64+CD206−) ATMs in females and males, respectively. Our data suggest rapamycin may achieve life-span extension in part through adipose tissue inflammation. Additionally, HET3 mice exhibit a spectrum of age-associated changes in the gWAT, but acarbose and 17-α estradiol do not strongly alter these phenotypes—suggesting that acarbose and 17- α estradiol may not influence life span through mechanisms involving adipose tissue inflammation.

scholarly journals Adipose tissue supports normalization of macrophage and liver lipid handling in obesity reversal

2017 ◽  
Vol 233 (3) ◽  
pp. 293-305 ◽  
Author(s):  
Maayan Vatarescu ◽  
Sapir Bechor ◽  
Yulia Haim ◽  
Tal Pecht ◽  
Tanya Tarnovscki ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Ex Vivo ◽  
Liver Lipid ◽  
Glucose Production ◽  
Whole Body ◽  
Adipose Tissue Inflammation ◽  
Cellular Lipid ◽  
Rapid Improvement ◽  
Tissue Inflammation ◽  
Tissue Macrophage

Adipose tissue inflammation and dysfunction are considered central in the pathogenesis of obesity-related dysmetabolism, but their role in the rapid metabolic recovery upon obesity reversal is less well defined. We hypothesized that changes in adipose tissue endocrine and paracrine mechanisms may support the rapid improvement of obesity-induced impairment in cellular lipid handling. C57Bl-6J mice were fed ad libitum either normal chow (NC) or high-fat diet (HFF) for 10 weeks. A dietary obesity reversal group was fed HFF for 8 weeks and then switched to NC for 2 weeks (HFF→NC). Whole-body glucose homeostasis rapidly nearly normalized in the HFF→NC mice (fasting glucose and insulin fully normalized, glucose and insulin tolerance tests reversed 82% to the NC group levels). During 2 weeks of the dietary reversal, the liver was significantly cleared from ectopic fat, and functionally, glucose production from pyruvate, alanine or fructose was normalized. In contrast, adipose tissue inflammation (macrophage infiltration and polarization) largely remained as in HFF, though obesity-induced adipose tissue macrophage lipid accumulation decreased by ~50%, and adipose tissue MAP kinase hyperactivation was reversed. Ex vivo, mild changes in adipose tissue adipocytokine secretion profile were noted. These corresponded to partial or full reversal of the excess cellular lipid droplet accumulation induced by HFF adipose tissue conditioned media in hepatoma or macrophage cells, respectively. We propose that early after initiating reversal of nutritional obesity, rapid metabolic normalization largely precedes resolution of adipose tissue inflammation. Nevertheless, we demonstrate a hitherto unrecognized contribution of adipose tissue to the rapid improvement in lipid handling by the liver and by macrophages.

scholarly journals Adipocyte-Derived Lactate Potentiates Obesity-Evoked Adipose Macrophage Inflammation

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A40-A41
Author(s):  
Xiaoyan Hannah Hui ◽  
Tianshi Feng
Keyword(s):  
Adipose Tissue ◽  
Lactate Level ◽  
Macrophage Polarization ◽  
Lactate Production ◽  
Physiological Role ◽  
Adipose Tissue Inflammation ◽  
Tissue Inflammation ◽  
Adipose Inflammation

Abstract Introduction: Obesity is characterized by mobilization of macrophage inflammation, which represents the major events of obesity-associated adipose tissue inflammation. . On the other hand, lactate accumulation in adipose tissue long been observed. However, whether elevation of lactate plays an essential role in adipose inflammation is not known. In this study, we sought to examine the intermediary role of lactate in macrophage polarization and adipose inflammation upon obesity. Method: Lactate level and activity of lactate dehydrogense (LDH), the key enzyme of lactate production, were measured by biochemical assays. Adipocyte- and macrophage- specific Ldha knock out mice were constructed by cre-LoxP system to study the physiological role of lactate in diet induced obesity. Macrophage polarization and inflammation were examined by western blotting and Q-PCR. Results: Lactate and LDH activity were selectively upregulated in adipose tissues of obese mice. Adipocyte-, but not macrophage-selective deletion of LDHA, led to a significant improvement of adipose inflammation and metabolic dysfunctions. In vitro experiments showed that the lactate promoted M1 polarization through direct interation and inhibition of the PHD2, which subsequently stabilizes HIF-1alpha. In addition, a positive correlation between adipose lactate level and adipose tissue inflammation was found in obese patients. Conclusion: In obese condition, increased production of lactate from adipocytes enhances adipose tissue inflammation by promoting the proinflammatory polarization of adipose macrophages.

scholarly journals Role of microRNA in CB1 antagonist–mediated regulation of adipose tissue macrophage polarization and chemotaxis during diet-induced obesity

2019 ◽  
Vol 294 (19) ◽  
pp. 7669-7681 ◽  
Author(s):  
Pegah Mehrpouya-Bahrami ◽  
Kathryn Miranda ◽  
Narendra P. Singh ◽  
Elizabeth E. Zumbrun ◽  
Mitzi Nagarkatti ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Macrophage Polarization ◽  
Tissue Macrophage ◽  
Adipose Tissue Macrophage ◽  
Diet Induced Obesity ◽  
Cb1 Antagonist
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