scholarly journals Apoptosis of hematopoietic progenitor-derived adipose tissue–resident macrophages contributes to insulin resistance after myocardial infarction

2020 ◽  
Vol 12 (553) ◽  
pp. eaaw0638 ◽  
Author(s):  
Sathish Babu Vasamsetti ◽  
Emilie Coppin ◽  
Xinyi Zhang ◽  
Jonathan Florentin ◽  
Sasha Koul ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Insulin Resistance ◽  
Adipose Tissue ◽  
Mouse Models ◽  
De Novo ◽  
Hematopoietic Progenitor ◽  
Resident Macrophage ◽  
Systemic Insulin Resistance ◽  
Macrophage Apoptosis ◽  
St Elevation

Patients with insulin resistance have high risk of cardiovascular disease such as myocardial infarction (MI). However, it is not known whether MI can initiate or aggravate insulin resistance. We observed that patients with ST-elevation MI and mice with MI had de novo hyperglycemia and features of insulin resistance, respectively. In mouse models of both myocardial and skeletal muscle injury, we observed that the number of visceral adipose tissue (VAT)–resident macrophages decreased because of apoptosis after these distant organ injuries. Patients displayed a similar decrease in VAT-resident macrophage numbers and developed systemic insulin resistance after ST-elevation MI. Loss of VAT-resident macrophages after MI injury led to systemic insulin resistance in non-diabetic mice. Danger signaling–associated protein high mobility group box 1 was released by the dead myocardium after MI in rodents and triggered macrophage apoptosis via Toll-like receptor 4. The VAT-resident macrophage population in the steady state in mice was transcriptomically distinct from macrophages in the brain, skin, kidney, bone marrow, lungs, and liver and was derived from hematopoietic progenitor cells just after birth. Mechanistically, VAT-resident macrophage apoptosis and de novo insulin resistance in mouse models of MI were linked to diminished concentrations of macrophage colony-stimulating factor and adiponectin. Collectively, these findings demonstrate a previously unappreciated role of adipose tissue–resident macrophages in sensing remote organ injury and promoting MI pathogenesis.

Abstract 13039: Loss of Visceral Adipose Tissue Macrophage Subsets Induces Myocardial Infarction Induced Insulin Resistance: Role of Adiponectin

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Sathish Babu B Vasamsetti ◽  
xinyi zhang ◽  
Emillie M Coppin ◽  
Jonathan Florentin ◽  
Sasha Koul ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Insulin Resistance ◽  
Adipose Tissue ◽  
Blood Glucose ◽  
Visceral Adipose Tissue ◽  
Fasting Blood Glucose ◽  
Glucose Levels ◽  
Blood Glucose Levels ◽  
Systemic Insulin Resistance ◽  
Visceral Adipose

Introduction: Myocardial infarction (MI) is the major cause of morbidity and mortality in the western world. Insulin resistance is a major complication in patients with MI. Hypothesis: Loss of visceral adipose tissue (VAT) resident macrophages in MI results in diminished adiponectin production causing systemic insulin resistance. Methods: To understand if MI results in insulin resistance, we analyzed UPMC patient records and identified patients who had normal fasting blood glucose levels on average 15 days before ST elevation myocardial infarction (STEMI) and checked their fasting blood glucose levels 30 days after STEMI. To understand the mechanisms of MI-induced insulin resistance, we used a mouse model of coronary ligation in C57BL/6 mice and analyzed the features of insulin resistance by measuring serum insulin, serum adiponectin, AKT activation status in the liver and muscle. Results: We found that 50% of non-diabetic patients (fasting blood glucose levels 99±2.5 mg/ dl) developed hyperglycemia (141±13 mg/dl) after MI, suggesting that MI causes insulin resistance. Consistently, mice with MI had higher fasting blood insulin, and reduced p-Akt levels in the liver and skeletal muscles confirming insulin resistance. Concomitantly, mice and patients with MI had reduced number of visceral adipose tissue (VAT) resident macrophages. In line with this, MI resulted in marked reduction in the level of macrophage colony stimulating factor (M-CSF), a cytokine required for tissue resident macrophage survival. M-CSF supplementation in mice with MI improved insulin sensitivity and decreased inflammatory phenotype of VAT macrophages. Furthermore, the systemic level of adiponectin, which is reported to augment insulin sensitivity, was profoundly reduced in mice after MI. Specific depletion of VAT resident macrophages resulted in lower levels of adiponectin in the serum, indicating that this macrophage subset is necessary for adiponectin production by adipocytes. Conclusions: Our data demonstrate that diminished M-CSF levels after MI triggers apoptosis of VAT resident macrophages, resulting in reduced adiponectin secretion and systemic insulin resistance.

scholarly journals Elevated and Correlated Expressions of miR-24, miR-30d, miR-146a, and SFRP-4 in Human Abdominal Adipose Tissue Play a Role in Adiposity and Insulin Resistance

2018 ◽  
Vol 2018 ◽  
pp. 1-7 ◽  
Author(s):  
Yury O. Nunez Lopez ◽  
Gabriella Garufi ◽  
Magdalena Pasarica ◽  
Attila A. Seyhan
Keyword(s):  
Insulin Resistance ◽  
Adipose Tissue ◽  
Insulin Sensitivity ◽  
Linear Models ◽  
Euglycemic Hyperinsulinemic Clamp ◽  
Abdominal Adipose Tissue ◽  
Systemic Insulin Resistance ◽  
Novel Association ◽  
Regulatory Loop

Objective. We explored the relationships among microRNAs (miRNAs) and SFRP4, as they relate to adipose tissue functions including lipolysis, glucose and glycerol turnover, and insulin sensitivity. Methods. Abdominal adipose tissue (AbdAT) levels of thirteen microRNAs (miRNAs), SFRP4, and VEGF in lean nondiabetic subjects (n=7), subjects with obesity (n=5), and subjects with obesity and type 2 diabetes (T2DM) (n=5) were measured by qPCR. Insulin sensitivity was measured by the euglycemic-hyperinsulinemic clamp. Osmium fixation and Coulter counting were used for adipocyte sizing. Data were analyzed using generalized linear models that adjusted for age, gender, and ethnicity. Results. AbdAT miR-24, miR-30d, and miR-146a were elevated in subjects with obesity (P<0.05) and T2DM (P<0.1) and positively correlated with measures of percent body fat by DXA (rmiR.24=0.894, rmiR.146a=0.883, P<0.05), and AbdAT SFRP4 (rmiR.30=0.93, rmiR.146a=0.88, P<0.05). These three miRNAs additionally correlated among themselves (rmiR.24~miR.146a=0.90, rmiR.30~miR.146a=0.85, P<0.01). Conclusions. This study suggests a novel association between the elevated levels of miRNAs miR-24, miR-30d, and miR-146a (apparently coregulated) and the level of SFRP4 transcript in AbdAT of subjects with obesity and T2DM. These molecules might be part of a regulatory loop involved in AbdAT remodeling/adiposity and systemic insulin resistance. This trial is registered with NCT00704197.

scholarly journals The glucose dysmetabolism in the acute phase of non-diabetic ST-elevation myocardial infarction: from insulin resistance to hyperglycemia

2011 ◽  
Vol 50 (3) ◽  
pp. 293-300 ◽  
Author(s):  
Chiara Lazzeri ◽  
Serafina Valente ◽  
Marco Chiostri ◽  
Paola Attanà ◽  
Claudio Picariello ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Insulin Resistance ◽  
Acute Phase ◽  
St Elevation Myocardial Infarction ◽  
St Elevation

scholarly journals Obesity-related hypoxia via miR-128 decreases insulin-receptor expression in human and mouse adipose tissue promoting systemic insulin resistance

EBioMedicine ◽  
2020 ◽  
Vol 59 ◽  
pp. 102912 ◽  
Author(s):  
Biagio Arcidiacono ◽  
Eusebio Chiefari ◽  
Anna Foryst-Ludwig ◽  
Giuseppe Currò ◽  
Giuseppe Navarra ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Adipose Tissue ◽  
Insulin Receptor ◽  
Receptor Expression ◽  
Systemic Insulin Resistance ◽  
Insulin Receptor Expression ◽  
Human And Mouse

scholarly journals RBP4 Activates Antigen-Presenting Cells, Leading to Adipose Tissue Inflammation and Systemic Insulin Resistance

2014 ◽  
Vol 19 (3) ◽  
pp. 512-526 ◽  
Author(s):  
Pedro M. Moraes-Vieira ◽  
Mark M. Yore ◽  
Peter M. Dwyer ◽  
Ismail Syed ◽  
Pratik Aryal ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Adipose Tissue ◽  
Antigen Presenting Cells ◽  
Adipose Tissue Inflammation ◽  
Tissue Inflammation ◽  
Systemic Insulin Resistance ◽  
Antigen Presenting

Relation of Quantity of Subepicardial Adipose Tissue to Infarct Size in Patients With ST-Elevation Myocardial Infarction

2017 ◽  
Vol 119 (12) ◽  
pp. 1972-1978 ◽  
Author(s):  
Loïc Bière ◽  
Vianney Behaghel ◽  
Victor Mateus ◽  
Antonildes Assunção ◽  
Christoph Gräni ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Adipose Tissue ◽  
Infarct Size ◽  
St Elevation Myocardial Infarction ◽  
St Elevation

scholarly journals Multiomics reveal unique signatures of human epiploic adipose tissue related to systemic insulin resistance

Gut ◽  
2021 ◽  
pp. gutjnl-2021-324603
Author(s):  
Laura Krieg ◽  
Konrad Didt ◽  
Isabel Karkossa ◽  
Stephan H Bernhart ◽  
Stephanie Kehr ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Adipose Tissue ◽  
Gastric Bypass Surgery ◽  
Whole Body ◽  
Expression Levels ◽  
Entire Cohort ◽  
Fat Depots ◽  
Systemic Insulin Resistance ◽  
Whole Body Metabolism

ObjectiveHuman white adipose tissue (AT) is a metabolically active organ with distinct depot-specific functions. Despite their locations close to the gastrointestinal tract, mesenteric AT and epiploic AT (epiAT) have only scarcely been investigated. Here, we aim to characterise these ATs in-depth and estimate their contribution to alterations in whole-body metabolism.DesignMesenteric, epiploic, omental and abdominal subcutaneous ATs were collected from 70 patients with obesity undergoing Roux-en-Y gastric bypass surgery. The metabolically well-characterised cohort included nine subjects with insulin sensitive (IS) obesity, whose AT samples were analysed in a multiomics approach, including methylome, transcriptome and proteome along with samples from subjects with insulin resistance (IR) matched for age, sex and body mass index (n=9). Findings implying differences between AT depots in these subgroups were validated in the entire cohort (n=70) by quantitative real-time PCR.ResultsWhile mesenteric AT exhibited signatures similar to those found in the omental depot, epiAT was distinct from all other studied fat depots. Multiomics allowed clear discrimination between the IS and IR states in all tissues. The highest discriminatory power between IS and IR was seen in epiAT, where profound differences in the regulation of developmental, metabolic and inflammatory pathways were observed. Gene expression levels of key molecules involved in AT function, metabolic homeostasis and inflammation revealed significant depot-specific differences with epiAT showing the highest expression levels.ConclusionMulti-omics epiAT signatures reflect systemic IR and obesity subphenotypes distinct from other fat depots. Our data suggest a previously unrecognised role of human epiploic fat in the context of obesity, impaired insulin sensitivity and related diseases.

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