Stress Augments Insulin Resistance and Prothrombotic State

Abstract

Stressors contribute to thrombosis and insulin resistance. Since obesity-related adipose inflammation is also involved in these pathological states, we assumed that stress correlates with adipose inflammation. Male mice were subjected to 2-week intermittent restraint stress. Expression of plasma lipids, monocyte/macrophage markers (CD11b, CD68, and F4/80), proinflammatory cytokines (monocyte chemoattractant protein-1 [MCP-1], tumor necrosis factor-α, and interleukin-6), adiponectin, heat shock protein 70.1 (HSP70.1), and coagulation factors (plasminogen activation inhibitor-1 [PAI-1] and tissue factor [TF]) in blood and inguinal white adipose tissue (WAT) was determined using immunohistochemistry, enzyme-linked immunosorbent assay, and RT-PCR, respectively. Glucose metabolism was assessed by glucose tolerance tests (GTTs) and insulin tolerance tests, and expression of insulin receptor substrate-1 (IRS-1) and glucose transporter 4 (GLUT4) in WAT. To examine effects of MCP-1 blockade, animals were treated with control or neutralizing antibody, or transplanted with control or 7ND (dominant-negative form of MCP-1)-overexpressing adipose-derived stromal cells (ADSCs). Stress increased monocyte accumulation, free fatty acids, proinflammatory cytokine, and HSP70.1 and reduced adiponectin. Adipose stromal cells highly expressed MCP-1. The stress-induced adipose inflammation increased PAI-1 and TF but did not give rise to thrombus formation. Without any changes in GTT, stress worsened insulin sensitivity and decreased IRS-1 and GLUT4 in WAT. Neutralizing antibody and 7ND-ADSCs reversed stress-induced adipose inflammation, procoagulant state, and insulin resistance. Stress evoked adipose inflammation to increase coagulation factors and impair insulin sensitivity through adipose-derived MCP-1.

Stressed-out dads can (metabolically) stress their kids

“…These male mice were then mated with females for 2 days ( Figure S1A). In agreement with previous observations (Depke et al, 2008;Uchida et al, 2012), stress-F0 mice exhibited a reduced body weight gain and increased blood glucose levels, compared with the control-F0 mice (Figures S1B-S1E). However, there were no significant differences in food intake, sperm density, motility, or the pregnancy rates of females between stress-and control-F0 mice (Figures S1F-S1I).…”

“…Eight-week-old C57BL/6 male mice were subjected to 14 days of daily restraint stress (stress-F0), as previously described (Uchida et al, 2012). These male mice were then mated with females for 2 days ( Figure S1A).…”

Effects of autologous adipose-derived stem cell infusion on type 2 diabetic rats

“…ber of mechanisms, including activation of inflammatory pathways, serine phosphorylation of the insulin receptor and insulin receptor substrate 1, and increased serum and hepatic triacylglycerol levels [37][38][39]. Our results demonstrated that ASC might improve insulin resistance by modulating inflammation and inflammatory cytokines.…”

The Immune System in Stroke: Clinical Challenges and Their Translation to Experimental Research

“…Stress-induced autonomic arousal contributes to various cardiovascular-(high blood pressure, increased heart rate) and metabolic alterations that are acknowledged independent risk factors for stroke. It has been shown recently that stress augments insulin resistance and evokes inflammation to increase coagulation factors through adipose tissue derived MCP-1 (Uchida et al 2012). …”