Adipose proinflammatory cytokine expression through sympathetic system is associated with hyperglycemia and insulin resistance in a rat ischemic stroke model.
Patients who experience acute ischemic stroke may develop hyperglycemia, even in the absence of diabetes, but the exact mechanisms are still unclear. Adipose tissue secretes numerous proinflammatory cytokines and is involved in the regulation of glucose metabolism. This study aimed to determine the effects of acute stroke on adipose inflammatory cytokine expression. In addition, because sympathetic activity is activated after acute stroke and catecholamines can regulate the expression of several adipocytokines, this study also evaluated whether alterations in adipose proinflammatory cytokines following acute stroke, if any, were medicated by sympathetic system. Acute ischemic brain injury was induced by ligating the right middle cerebral artery and bilateral common carotid arteries in male adult Sprague-Dawley rats. Adipose tumor necrosis factor-α (TNF-α) and monocyte chemoattractant protein-1 (MCP-1) mRNA and protein levels were determined by RT-PCR and enzyme-linked immunoassay, respectively. The stroke rats developed glucose intolerance on days 1 and 2 after cerebral ischemic injury. The fasting blood insulin levels and insulin resistance index measured by homeostasis model assessment were higher in the stroke rats compared with the sham group. Epididymal adipose TNF-α and MCP-1 mRNA and protein levels were elevated one- to twofold, in association with increased macrophage infiltration into the adipose tissue. When the rats were treated with a nonselective β-adrenergic receptor blocker, propranolol, before induction of cerebral ischemic injury, the acute stroke-induced increase in TNF-α and MCP-1 was blocked, and fasting blood insulin concentration and homeostasis model assessment-insulin resistance were decreased. These results suggest a potential role of adipose proinflammatory cytokines induced by the sympathetic nervous system in the pathogenesis of glucose metabolic disorder in rats with acute ischemic stroke.
Division of Family Medicine, Taichung Veterans General Hospital, Taichung, Taiwan.
Ya-Yu
YY
Wang
Shih-Yi
SY
Lin
Yu-Han
YH
Chuang
Chun-Jung
CJ
Chen
Kwong-Chung
KC
Tung
Wayne Huey-Herng
WH
Sheu
D052436:Adipose Tissue, White / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D002545:Brain Ischemia / Q000097:blood / Q000378:metabolism / Q000503:physiopathology*; D018932:Chemokine CCL2 / Q000235:genetics / Q000378:metabolism; D016207:Cytokines / Q000097:blood / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects; D018149:Glucose Intolerance / Q000209:etiology; D006943:Hyperglycemia / Q000097:blood / Q000209:etiology / Q000378:metabolism*; D018836:Inflammation Mediators / Q000378:metabolism; D007333:Insulin Resistance; D008264:Macrophages / Q000378:metabolism; D008297:Male; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D020521:Stroke / Q000097:blood / Q000378:metabolism / Q000503:physiopathology*; D013564:Sympathetic Nervous System / Q000187:drug effects / Q000502:physiology*; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism
D000319:Adrenergic beta-Antagonists; C491766:Ccl2 protein, rat; D018932:Chemokine CCL2; D016207:Cytokines; D018836:Inflammation Mediators; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha