Adipose tissue and metabolic and inflammatory responses to stroke are altered in obese mice

Disease Models & Mechanisms

Graham Mullard¹  Garth J. Cooper¹  Katherine A. Hollywood¹  Warwick B. Dunn¹  Michael J. Haley²  Catherine B. Lawrence² 

[1] Centre for Endocrinology and Diabetes, Institute of Human Development, Faculty of Biological, Medical and Human Sciences, University of Manchester, Manchester, M13 9WL, UK;Faculty of Biological, Medical and Human Sciences, Manchester Academic Health Science Centre, University of Manchester, Manchester, M13 9PT, UK;

关键词: Stroke;    Metabolomics;    Obesity;    Lipids;    Inflammation;    Adipokines;   

DOI  :  10.1242/dmm.030411

来源: DOAJ

【 摘 要 】

Obesity is an independent risk factor for stroke, although several clinical studies have reported that obesity improves stroke outcome. Obesity is hypothesised to aid recovery by protecting against post-stroke catabolism. We therefore assessed whether obese mice had an altered metabolic and inflammatory response to stroke. Obese ob/ob mice underwent a 20-min middle cerebral artery occlusion and 24-h reperfusion. Lipid metabolism and expression of inflammatory cytokines were assessed in the plasma, liver and adipose tissue. The obese-specific metabolic response to stroke was assessed in plasma using non-targeted ultra-high performance liquid chromatography-mass spectrometry (UHPLC-MS) metabolomics coupled with univariate and multivariate analysis. Obesity had no effect on the extent of weight loss 24 h after stroke but affected the metabolic and inflammatory responses to stroke, predominantly affecting lipid metabolism. Specifically, obese mice had increases in plasma free fatty acids and expression of adipose lipolytic enzymes. Metabolomics identified several classes of metabolites affected by stroke in obese mice, including fatty acids and membrane lipids (glycerophospholipids, lysophospholipids and sphingolipids). Obesity also featured increases in inflammatory cytokines in the plasma and adipose tissue. Overall, these results demonstrate that obesity affected the acute metabolic and inflammatory response to stroke and suggest a potential role for adipose tissue in this effect. These findings could have implications for longer-term recovery and also further highlight the importance of considering comorbidities in preclinical stroke research, especially when identifying biomarkers for stroke. However, further work is required to assess whether these changes translate into long-term effects on recovery.

【 授权许可】

Unknown