scholarly journals Myeloid Sirtuin 6 Deficiency Causes Insulin Resistance in High-Fat Diet–Fed Mice by Eliciting Macrophage Polarization Toward an M1 Phenotype

Diabetes ◽  
2017 ◽  
Vol 66 (10) ◽  
pp. 2659-2668 ◽  
Author(s):  
Youngyi Lee ◽  
Sun-O Ka ◽  
Hye-Na Cha ◽  
Yu-Na Chae ◽  
Mi-Kyung Kim ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
High Fat Diet ◽  
Macrophage Polarization ◽  
High Fat ◽  
M1 Phenotype

scholarly journals Kdm2a deficiency in macrophages enhances thermogenesis to protect mice against HFD-induced obesity by enhancing H3K36me2 at the Pparg locus

2021 ◽  
Author(s):  
Longmin Chen ◽  
Jing Zhang ◽  
Yuan Zou ◽  
Faxi Wang ◽  
Jingyi Li ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
High Fat Diet ◽  
Macrophage Polarization ◽  
Fatty Acid Uptake ◽  
Chromatin Accessibility ◽  
Acid Uptake ◽  
High Fat ◽  
M2 Polarization ◽  
Adipose Tissue Macrophages ◽  
Cold Challenge

AbstractKdm2a catalyzes H3K36me2 demethylation to play an intriguing epigenetic regulatory role in cell proliferation, differentiation, and apoptosis. Herein we found that myeloid-specific knockout of Kdm2a (LysM-Cre-Kdm2af/f, Kdm2a−/−) promoted macrophage M2 program by reprograming metabolic homeostasis through enhancing fatty acid uptake and lipolysis. Kdm2a−/− increased H3K36me2 levels at the Pparg locus along with augmented chromatin accessibility and Stat6 recruitment, which rendered macrophages with preferential M2 polarization. Therefore, the Kdm2a−/− mice were highly protected from high-fat diet (HFD)-induced obesity, insulin resistance, and hepatic steatosis, and featured by the reduced accumulation of adipose tissue macrophages and repressed chronic inflammation following HFD challenge. Particularly, Kdm2a−/− macrophages provided a microenvironment in favor of thermogenesis. Upon HFD or cold challenge, the Kdm2a−/− mice manifested higher capacity for inducing adipose browning and beiging to promote energy expenditure. Collectively, our findings demonstrate the importance of Kdm2a-mediated H3K36 demethylation in orchestrating macrophage polarization, providing novel insight that targeting Kdm2a in macrophages could be a viable therapeutic approach against obesity 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.

scholarly journals Improvement of Adipose Macrophage Polarization in High Fat Diet-Induced Obese GHSR Knockout Mice

2018 ◽  
Vol 2018 ◽  
pp. 1-8 ◽  
Author(s):  
Fang Yuan ◽  
Jian Ma ◽  
Xinxin Xiang ◽  
He Lan ◽  
Yanhui Xu ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Adipose Tissue ◽  
High Fat Diet ◽  
Macrophage Polarization ◽  
Interstitial Cells ◽  
Epididymal Adipose Tissue ◽  
Mrna Levels ◽  
High Fat ◽  
Growth Hormone Secretagogue ◽  
Anti Inflammatory

Purpose. Adipose tissue inflammation is the key linking obesity to insulin resistance. Over 50% of the interstitial cells in adipose tissue are macrophages, which produce inflammatory cytokines and therefore play an important role in the progression of insulin resistance. Within this classification view, macrophage biology is driven by two polarization phenotypes, M1 (proinflammatory) and M2 (anti-inflammatory). The unique functional receptor of ghrelin, growth hormone secretagogue receptor (GHSR), is a classic seven-transmembrane G protein-coupled receptor that is linked to multiple intracellular signaling pathways. Knockout of GHSR improves the obesity and glucose metabolic disorders, suggesting a crucial role of ghrelin activity in insulin resistance. Here, we discussed whether macrophage polarization phenotypes in adipose tissue were changed in GHSR knockout (GHSR-/-) mice. Methods. GHSR-/- mice were fed with normal chow diet (NCD) or high fat diet (HFD). Markers of different macrophage polarization phenotypes were detected by real-time RT-PCR. Results. The size of adipocytes decreased and interstitial cells, especially infiltrated macrophages, reduced in epididymal adipose tissue of GHSR-/- mice fed with HFD. Compared with wild type mice, the mRNA levels of inflammatory adipokines such as resistin, IL-6, and PAI-1 were significantly lower in epididymal adipose tissue of GHSR-/- mice, whereas anti-inflammatory adipokine, adiponectin, was significantly higher. M1 markers, MCP-1, TNF-α, and iNOS, were significantly lower in epididymal adipose tissue of GHSR-/- mice, whereas M2 markers, Arg-1, Mgl-1, were Mrc1, were significantly higher. Conclusion. The GHSR-/- mice fed with HFD showed suppressed adipose inflammation, reduced macrophage infiltration, and enhanced M2 polarization of macrophages in adipose tissue, which improved insulin sensitivity.

Altered bone metabolism after high fat diet and exercise: role of Wnt signaling and insulin resistance

2016 ◽  
Author(s):  
Ann-Kristin Picke ◽  
Lykke Sylow ◽  
Lisbeth L V Moller ◽  
Rasmus Kjobsted ◽  
Erik Richter ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Wnt Signaling ◽  
Bone Metabolism ◽  
High Fat Diet ◽  
High Fat ◽  
Diet And Exercise

Dissociation between high fat diet-induced obesity (DIO) and insulin resistance: lessons from AHNAK knockout mice

2013 ◽  
Author(s):  
Maya Ramdas ◽  
Chava Harel ◽  
Natalia Krits ◽  
Michal Armoni ◽  
Eddy Karnieli
Keyword(s):  
Insulin Resistance ◽  
Knockout Mice ◽  
High Fat Diet ◽  
High Fat ◽  
Diet Induced Obesity

Odontella aurita-enriched high-fat diet prevents high-fat diet induced insulin resistance

2015 ◽  
Author(s):  
Hamza Amine ◽  
Yacir Benomar ◽  
Nadia Meskini ◽  
Mohammed Taouis
Keyword(s):  
Insulin Resistance ◽  
High Fat Diet ◽  
High Fat ◽  
Odontella Aurita

165-OR: The Mechanisms by Which Adiponectin Reverses Insulin Resistance in High-Fat Diet Fed Mice

Diabetes ◽  
2019 ◽  
Vol 68 (Supplement 1) ◽  
pp. 165-OR
Author(s):  
XIRUO LI ◽  
DONGYAN ZHANG ◽  
RACHEL J. PERRY ◽  
DANIEL F. VATNER ◽  
LEIGH GOEDEKE ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
High Fat Diet ◽  
High Fat

Insulin resistance of muscle glucose transport in rats fed a high-fat diet: a reevaluation

Diabetes ◽  
1997 ◽  
Vol 46 (11) ◽  
pp. 1761-1767 ◽  
Author(s):  
D. H. Han ◽  
P. A. Hansen ◽  
H. H. Host ◽  
J. O. Holloszy
Keyword(s):  
Insulin Resistance ◽  
Glucose Transport ◽  
High Fat Diet ◽  
High Fat ◽  
Muscle Glucose Transport
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