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

• Published in: Circulation (New York, N.Y.) N.Y.), 2020-11, Vol.142 (Suppl_3 Suppl 3), p.A13039-A13039
• Main Authors: Vasamsetti, Sathish Babu B, zhang, xinyi, Coppin, Emillie M, Florentin, Jonathan, Koul, Sasha, Gotberg, Matthias, Clugston, Andrew S, Thoma, Floyd, Sembrat, John, Bullock, Grant C, Kostka, Dennis, St. Croix, Claudette M, Chattopadhyay, Ansuman, rojas, mauricio, Mulukutla, Suresh, Dutta, Partha
• Format: Article
• Language: English
• ISSN: 0009-7322; 1524-4539
• DOI: 10.1161/circ.142.suppl_3.13039

IntroductionMyocardial infarction (MI) is the major cause of morbidity and mortality in the western world. Insulin resistance is a major complication in patients with MI. HypothesisLoss of visceral adipose tissue (VAT) resident macrophages in MI results in diminished adiponectin production causing systemic insulin resistance. MethodsTo 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. ResultsWe 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. ConclusionsOur data demonstrate that diminished M-CSF levels after MI triggers apoptosis of VAT resident macrophages, resulting in reduced adiponectin secretion and systemic insulin resistance.