scholarly journals Alcohol-induced adipose tissue macrophage phenotypic switching is independent of myeloid Toll-like receptor 4 expression

2019 ◽  
Vol 317 (4) ◽  
pp. C687-C700 ◽  
Author(s):  
Melissa A. Fulham ◽  
Anuradha Ratna ◽  
Rachel M. Gerstein ◽  
Evelyn A. Kurt-Jones ◽  
Pranoti Mandrekar
Keyword(s):  
Adipose Tissue ◽  
Myeloid Cells ◽  
Alcohol Exposure ◽  
Phenotypic Switching ◽  
Adipose Tissue Inflammation ◽  
Toll Like Receptor ◽  
Tlr4 Expression ◽  
Toll Like Receptor 4 ◽  
Tissue Inflammation ◽  
Adipose Tissue Macrophages

Alcoholic liver disease results from a combination of immune and metabolic pathogenic events. In addition to liver injury, chronic alcohol consumption also causes adipose tissue inflammation. The specific immune mechanisms that drive this process are unknown. Here, we sought to determine the role of the innate immune receptor Toll-like receptor 4 (TLR4) in alcohol-induced adipose tissue inflammation. Using a model of chronic, multiple-binge alcohol exposure, we showed that alcohol-mediated accumulation of proinflammatory adipose tissue macrophages was absent in global TLR4 knockout mice. Proinflammatory macrophage accumulation did not depend on macrophage TLR4 expression; LysMCre-driven deletion of Tlr4 from myeloid cells did not affect circulating endotoxin or the accumulation of M1 macrophages in adipose tissue following alcohol exposure. Proinflammatory cytokine/chemokine production in the adipose stromal vascular fraction also occurred independently of TLR4. Finally, the levels of other adipose immune cells, such as dendritic cells, neutrophils, B cells, and T cells, were modulated by chronic, multiple-binge alcohol and the presence of TLR4. Together, these data indicate that TLR4 expression on cells, other than myeloid cells, is important for the alcohol-induced increase in proinflammatory adipose tissue macrophages.

scholarly journals Toll-like receptor 4 (TLR4) deficient mice are protected from adipose tissue inflammation in aging

Aging ◽  
2017 ◽  
Vol 9 (9) ◽  
pp. 1971-1982 ◽  
Author(s):  
Amiya K. Ghosh ◽  
Martin O’Brien ◽  
Theresa Mau ◽  
Raymond Yung
Keyword(s):  
Adipose Tissue ◽  
Adipose Tissue Inflammation ◽  
Toll Like Receptor ◽  
Toll Like Receptor 4 ◽  
Tissue Inflammation ◽  
Deficient Mice

Attenuation of obesity-induced adipose tissue inflammation in C3H/HeJ mice carrying a Toll-like receptor 4 mutation

2007 ◽  
Vol 354 (1) ◽  
pp. 45-49 ◽  
Author(s):  
Takayoshi Suganami ◽  
Tae Mieda ◽  
Michiko Itoh ◽  
Yuri Shimoda ◽  
Yasutomi Kamei ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Adipose Tissue Inflammation ◽  
Toll Like Receptor ◽  
Toll Like Receptor 4 ◽  
Tissue Inflammation

scholarly journals The role of uncoupling protein 2 in macrophages and its impact on obesity-induced adipose tissue inflammation and insulin resistance

2020 ◽  
Vol 295 (51) ◽  
pp. 17535-17548
Author(s):  
Xanthe A. M. H. van Dierendonck ◽  
Tiphaine Sancerni ◽  
Marie-Clotilde Alves-Guerra ◽  
Rinke Stienstra
Keyword(s):  
Insulin Resistance ◽  
Adipose Tissue ◽  
Macrophage Activation ◽  
Uncoupling Protein ◽  
Uncoupling Protein 2 ◽  
Adipose Tissue Inflammation ◽  
Tissue Inflammation ◽  
Obesity And Diabetes ◽  
Adipose Tissue Macrophages

The development of a chronic, low-grade inflammation originating from adipose tissue in obese subjects is widely recognized to induce insulin resistance, leading to the development of type 2 diabetes. The adipose tissue microenvironment drives specific metabolic reprogramming of adipose tissue macrophages, contributing to the induction of tissue inflammation. Uncoupling protein 2 (UCP2), a mitochondrial anion carrier, is thought to separately modulate inflammatory and metabolic processes in macrophages and is up-regulated in macrophages in the context of obesity and diabetes. Here, we investigate the role of UCP2 in macrophage activation in the context of obesity-induced adipose tissue inflammation and insulin resistance. Using a myeloid-specific knockout of UCP2 (Ucp2ΔLysM), we found that UCP2 deficiency significantly increases glycolysis and oxidative respiration, both unstimulated and after inflammatory conditions. Strikingly, fatty acid loading abolished the metabolic differences between Ucp2ΔLysM macrophages and their floxed controls. Furthermore, Ucp2ΔLysM macrophages show attenuated pro-inflammatory responses toward Toll-like receptor-2 and -4 stimulation. To test the relevance of macrophage-specific Ucp2 deletion in vivo, Ucp2ΔLysM and Ucp2fl/fl mice were rendered obese and insulin resistant through high-fat feeding. Although no differences in adipose tissue inflammation or insulin resistance was found between the two genotypes, adipose tissue macrophages isolated from diet-induced obese Ucp2ΔLysM mice showed decreased TNFα secretion after ex vivo lipopolysaccharide stimulation compared with their Ucp2fl/fl littermates. Together, these results demonstrate that although UCP2 regulates both metabolism and the inflammatory response of macrophages, its activity is not crucial in shaping macrophage activation in the adipose tissue during obesity-induced insulin resistance.

scholarly journals Toll-like receptor 5 in obesity: The role of gut microbiota and adipose tissue inflammation

Obesity ◽  
2015 ◽  
Vol 23 (3) ◽  
pp. 581-590 ◽  
Author(s):  
Satu Pekkala ◽  
Eveliina Munukka ◽  
Lingjia Kong ◽  
Eija Pöllänen ◽  
Reija Autio ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Gut Microbiota ◽  
Adipose Tissue Inflammation ◽  
Toll Like Receptor ◽  
Tissue Inflammation ◽  
Toll Like Receptor 5

Inflammation, but not recruitment, of adipose tissue macrophages requires signalling through Mac-1 (CD11b/CD18) in diet-induced obesity (DIO)

2017 ◽  
Vol 117 (02) ◽  
pp. 325-338 ◽  
Author(s):  
Dennis Wolf ◽  
Nora Bukosza ◽  
David Engel ◽  
Marjorie Poggi ◽  
Felix Jehle ◽  
...  
Keyword(s):  
Gene Expression ◽  
Skeletal Muscle ◽  
Adipose Tissue ◽  
Adipose Tissue Inflammation ◽  
Inflammatory Gene Expression ◽  
Tissue Inflammation ◽  
Inflammatory Gene ◽  
Diet Induced Obesity ◽  
Adipose Tissue Macrophages ◽  
Cell Accumulation

SummaryCell accumulation is a prerequisite for adipose tissue inflammation. The leukocyte integrin Mac-1 (CD11b/CD18, αMβ2) is a classic adhesion receptor critically regulating inflammatory cell recruitment. Here, we tested the hypothesis that a genetic deficiency and a therapeutic modulation of Mac-1 regulate adipose tissue inflammation in a mouse model of diet-induced obesity (DIO). C57Bl6/J mice genetically deficient (Mac-1-/-) or competent for Mac-1 (WT) consumed a high fat diet for 20 weeks. Surprisingly, Mac-1-/- mice presented with increased diet-induced weight gain, decreased insulin sensitivity in skeletal muscle and in the liver in insulin-clamps, insulin secretion deficiency and elevated glucose levels in fasting animals, and dyslipidaemia. Unexpectedly, accumulation of adipose tissue macrophages (ATMs) was unaffected, while gene expression indicated less inflamed adipose tissue and macrophages in Mac-1-/- mice. In contrast, inflammatory gene expression at distant locations, such as in skeletal muscle, was not changed. Treatment of ATMs with an agonistic anti-Mac-1 antibody, M1/70, induced pro-inflammatory genes in cell culture. In vivo, treatment with M1/70 induced a hyper-inflammatory phenotype with increased expression of IL-6 and MCP-1, whereas accumulation of ATMs did not change. Finally, inhibition of Mac-1’s adhesive interaction to CD40L by the peptide inhibitor cM7 did not affect myeloid cell accumulation in adipose tissue. We present the surprising finding that adhesive properties of the leukocyte integrin Mac-1 are not required for macrophage accumulation in adipose tissue. Instead, Mac-1 modulates inflammatory gene expression in macrophages. These findings question the net effect of integrin blockade in cardio-metabolic disease.D. W., N. B., and D. E. equally contributed to this work.K. P., E. L., and A. Z. share senior authorship.Note: The review process for this manuscript was fully handled by Gregory Y. H. Lip, Editor in Chief.Supplementary Material to this article is available online at www.thrombosis-online.com.

scholarly journals Identification of a Cytochrome P4502E1/Bid/C1q-dependent Axis Mediating Inflammation in Adipose Tissue after Chronic Ethanol Feeding to Mice

2011 ◽  
Vol 286 (41) ◽  
pp. 35989-35997 ◽  
Author(s):  
Becky M. Sebastian ◽  
Sanjoy Roychowdhury ◽  
Hui Tang ◽  
Antoinette D. Hillian ◽  
Ariel E. Feldstein ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Alcohol Exposure ◽  
Chronic Ethanol ◽  
Adipose Tissue Inflammation ◽  
Wild Type ◽  
Complement Protein ◽  
Apoptotic Pathway ◽  
Tissue Inflammation ◽  
Cytochrome P4502e1 ◽  
Ethanol Feeding

Chronic, heavy alcohol exposure results in inflammation in adipose tissue, insulin resistance, and liver injury. Here we have identified a CYP2E1/Bid/C1q-dependent pathway that is activated in response to chronic ethanol and is required for the development of inflammation in adipose tissue. Ethanol feeding for 25 days to wild-type (C57BL/6J) mice increased expression of multiple markers of adipose tissue inflammation relative to pair-fed controls independent of increased body weight or adipocyte size. Ethanol feeding increased the expression of CYP2E1 in adipocytes, but not stromal vascular cells, in adipose tissue and Cyp2e1−/− mice were protected from adipose tissue inflammation in response to ethanol. Ethanol feeding also increased the number of TUNEL-positive nuclei in adipose tissue of wild-type mice but not in Cyp2e1−/− or Bid−/− mice. Apoptosis contributed to adipose inflammation, as the expression of multiple inflammatory markers was decreased in mice lacking the Bid-dependent apoptotic pathway. The complement protein C1q binds to apoptotic cells, facilitating their clearance and activating complement. Making use of C1q-deficient mice, we found that activation of complement via C1q provided the critical link between CYP2E1/Bid-dependent apoptosis and onset of adipose tissue inflammation in response to chronic ethanol. In summary, chronic ethanol increases CYP2E1 activity in adipose, leading to Bid-mediated apoptosis and activation of complement via C1q, finally resulting in adipose tissue inflammation. Taken together, these data identify a novel mechanism for the development of adipose tissue inflammation that likely contributes to the pathophysiological effects of ethanol.

scholarly journals Nrf2 deficiency in myeloid cells is not sufficient to protect mice from high-fat diet-induced adipose tissue inflammation and insulin resistance

2012 ◽  
Vol 52 (9) ◽  
pp. 1708-1715 ◽  
Author(s):  
Akshaya K. Meher ◽  
Poonam R. Sharma ◽  
Vitor A. Lira ◽  
Masayuki Yamamoto ◽  
Thomas W. Kensler ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Adipose Tissue ◽  
High Fat Diet ◽  
Myeloid Cells ◽  
Adipose Tissue Inflammation ◽  
High Fat ◽  
Tissue Inflammation

scholarly journals Loss of Pdk1-Foxo1 Signaling in Myeloid Cells Predisposes to Adipose Tissue Inflammation and Insulin Resistance

Diabetes ◽  
2012 ◽  
Vol 61 (8) ◽  
pp. 1935-1948 ◽  
Author(s):  
Y. Kawano ◽  
J. Nakae ◽  
N. Watanabe ◽  
S. Fujisaka ◽  
K. Iskandar ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Adipose Tissue ◽  
Myeloid Cells ◽  
Adipose Tissue Inflammation ◽  
Tissue Inflammation

scholarly journals Hedgehog signalling in myeloid cells impacts on body weight, adipose tissue inflammation and glucose metabolism

Diabetologia ◽  
2017 ◽  
Vol 60 (5) ◽  
pp. 889-899 ◽  
Author(s):  
Julia Braune ◽  
Ulrike Weyer ◽  
Madlen Matz-Soja ◽  
Constance Hobusch ◽  
Matthias Kern ◽  
...  
Keyword(s):  
Body Weight ◽  
Adipose Tissue ◽  
Glucose Metabolism ◽  
Myeloid Cells ◽  
Adipose Tissue Inflammation ◽  
Hedgehog Signalling ◽  
Tissue Inflammation
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