Stress augments insulin resistance and prothrombotic state: Role of visceral adipose-derived monocyte chemoattractant protein-1

Yasuhiro Uchida, Kyosuke Takeshita, Koji Yamamoto, Ryosuke Kikuchi, Takayuki Nakayama, Mieko Nomura, Xian Wu Cheng, Kensuke Egashira, Tadashi Matsushita, Hideo Nakamura, Toyoaki Murohara

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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.

Original languageEnglish
Pages (from-to)1552-1561
Number of pages10
JournalDiabetes
Volume61
Issue number6
DOIs
Publication statusPublished - Jun 1 2012

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Chemokine CCL2
Insulin Resistance
White Adipose Tissue
Inflammation
Stromal Cells
Insulin Receptor Substrate Proteins
Blood Coagulation Factors
Facilitative Glucose Transport Proteins
Plasminogen
Adiponectin
Thromboplastin
Glucose Tolerance Test
Neutralizing Antibodies
Monocytes
Thrombosis
Cytokines
Groin
Nonesterified Fatty Acids
Interleukin-6
Tumor Necrosis Factor-alpha

All Science Journal Classification (ASJC) codes

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

Cite this

Uchida, Y., Takeshita, K., Yamamoto, K., Kikuchi, R., Nakayama, T., Nomura, M., ... Murohara, T. (2012). Stress augments insulin resistance and prothrombotic state: Role of visceral adipose-derived monocyte chemoattractant protein-1. Diabetes, 61(6), 1552-1561. https://doi.org/10.2337/db11-0828

Stress augments insulin resistance and prothrombotic state : Role of visceral adipose-derived monocyte chemoattractant protein-1. / Uchida, Yasuhiro; Takeshita, Kyosuke; Yamamoto, Koji; Kikuchi, Ryosuke; Nakayama, Takayuki; Nomura, Mieko; Cheng, Xian Wu; Egashira, Kensuke; Matsushita, Tadashi; Nakamura, Hideo; Murohara, Toyoaki.

In: Diabetes, Vol. 61, No. 6, 01.06.2012, p. 1552-1561.

Research output: Contribution to journalArticle

Uchida, Y, Takeshita, K, Yamamoto, K, Kikuchi, R, Nakayama, T, Nomura, M, Cheng, XW, Egashira, K, Matsushita, T, Nakamura, H & Murohara, T 2012, 'Stress augments insulin resistance and prothrombotic state: Role of visceral adipose-derived monocyte chemoattractant protein-1', Diabetes, vol. 61, no. 6, pp. 1552-1561. https://doi.org/10.2337/db11-0828
Uchida, Yasuhiro ; Takeshita, Kyosuke ; Yamamoto, Koji ; Kikuchi, Ryosuke ; Nakayama, Takayuki ; Nomura, Mieko ; Cheng, Xian Wu ; Egashira, Kensuke ; Matsushita, Tadashi ; Nakamura, Hideo ; Murohara, Toyoaki. / Stress augments insulin resistance and prothrombotic state : Role of visceral adipose-derived monocyte chemoattractant protein-1. In: Diabetes. 2012 ; Vol. 61, No. 6. pp. 1552-1561.
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