Obesity Adiponectin and Prognosis of Ischemic Stroke From Bench to Beside—Basic and Clinical Studies

  • 吳 明修

Student thesis: Doctoral Thesis


Stroke is the second leading cause of death worldwide Obesity is a pandemic health problem in the world known to be associated with increased risk of death cardiovascular disease and diabetes mellitus and a recognized risk factor for stroke Obesity is a chronic inflammatory status for the body associated with activated immune cells and increasing pro-inflammatory cytokines and could exacerbate ischemic cerebral injury Paradoxically overweight and obesity are related to better survival benefit than normal weight which is termed as obesity paradox It has been studied in acute stroke with inconsistent even conflicting results Another question is whether the decreased mortality could lead to improved functional outcome Adiponectin (APN) secreted by adipose tissue is the most anti-inflammatory adipokine and vasoprotective against atherosclerosis The expression of adiponectin is dowregulated in obesity Adiponectin seems not to increase stroke risk Results from studies in assessing circulating adiponectin concentrations and the risk of stroke mortality are conflicting and inconsistent in its relationship with functional outcome The aim of my thesis is to investigate the role of obesity and adiponectin in the pathogenesis and prognosis of ischemic stroke In the bench work diet-induced obesity (DIO) rats received middle cerebral artery occlusion (MCAO) Pre-treatment with intra-striatal delivery of baculovirus-mediated APN expression reduced cerebral ischemic injury aggravated by obesity through down-regulation of adiponectin receptor 1 (AdipoR1) and up-regulation of adiponectin receptor 2 (AdipoR2) and down-regulation of p38 MAPK and caspase-3 as evidenced by reduced infarction volume neurological deficits blood-brain-barrier damage and neuronal apoptosis With data from the Taiwan Stroke Registry (TSR) 19 069 first-ever acute ischemic stroke patients were recruited and stratified by body mass index (BMI) and it was found that body weight was related to the prognosis of acute ischemic stroke Obesity paradox was partially demonstrated in Asian first-ever ischemic stroke patients Only overweight but not obese patients showed improved survival and functional outcome after stroke when compared with the normal weight Underweight had increased mortality and decreased functional outcome Clinically 229 patients were recruited in Chi-Mei Medical Center Liouying and it was showed that admission hyperadiponectinemia was related to worse prognosis 3 and 12 months after acute ischemic stroke With measurement of APN isoforms low admission serum high molecular weight APN was related to worse prognosis 1 3 6 and 12 months after acute ischemic stroke Also high serum admission globular form APN was related to worse prognosis 6 months after acute ischemic stroke I believe that results from these works could help to elucidate mechanisms of obesity and APN in cerebral ischemic injury and provide evidence in relating body weight to clinical care of acute ischemic stroke
Date of Award2017 Aug 5
Original languageEnglish
SupervisorChao-Ching Huang (Supervisor)

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