Prolonged diet-induced obesity in mice modifies the inflammatory response and leads to worse outcome after stroke
Tóm tắt
Obesity increases the risk for ischaemic stroke and is associated with worse outcome clinically and experimentally. Most experimental studies have used genetic models of obesity. Here, a more clinically relevant model, diet-induced obesity, was used to study the impact of obesity over time on the outcome and inflammatory response after stroke. Male C57BL/6 mice were maintained on a high-fat (60 % fat) or control (12 % fat) diet for 2, 3, 4 and 6 months when experimental stroke was induced by transient occlusion of the middle cerebral artery (MCAo) for either 20 (6-month diet) or 30 min (2-, 3-, 4- and 6-month diet). Ischaemic damage, blood–brain barrier (BBB) integrity, neutrophil number and chemokine expression in the brain were assessed at 24 h. Plasma chemokine levels (at 4 and 24 h) and neutrophil number in the liver (at 24 h) were measured. Physiological parameters (body weight and blood glucose) were measured in naïve control- and high-fat-fed mice at all time points and blood pressure at 3 and 6 months. Blood cell counts were also assessed in naïve 6-month control- and high-fat-fed mice. Mice fed a high-fat diet for 6 months had greater body weight, blood glucose and white and red blood cell count but no change in systolic blood pressure. After 4 and 6 months of high-fat feeding, and in the latter group with a 30-min (but not 20-min) occlusion of the MCA, obese mice had greater ischaemic brain damage. An increase in blood–brain barrier permeability, chemokine expression (CXCL-1 and CCL3), neutrophil number and microglia/macrophage cells was observed in the brains of 6-month high-fat-fed mice after 30-min MCAo. In response to stroke, chemokine (CXCL-1) expression in the plasma and liver was significantly different in obese mice (6-month high-fat fed), and a greater number of neutrophils were detected in the liver of control but not obese mice. The detrimental effects of diet-induced obesity on stroke were therefore dependent on the severity of obesity and length of ischaemic challenge. The altered inflammatory response in obese mice may play a key role in its negative impact on stroke.
Tài liệu tham khảo
Ankolekar S, Rewell S, Howells DW, Bath PMW. The influence of stroke risk factors and comorbidities on assessment of stroke therapies in humans and animals. Int J Stroke. 2012;7:386–97.
Neuhaus AA, Rabie T, Sutherland BA, Papadakis M, Hadley G, Cai R, et al. Importance of preclinical research in the development of neuroprotective strategies for ischemic stroke. JAMA Neurol. 2014;71:634–9.
Strazzullo P, D'Elia L, Cairella G, Garbagnati F, Cappuccio FP, Scalfi L. Excess body weight and incidence of stroke: meta-analysis of prospective studies with 2 million participants. Stroke. 2010;41:e418–26.
Kumari R, Willing LB, Patel SD, Baskerville KA, Simpson IA. Increased cerebral matrix metalloprotease-9 activity is associated with compromised recovery in the diabetic db/db mouse following a stroke. J Neurochem. 2011;119:1029–40.
Nagai N, Van Hoef B, Lijnen HR. Plasminogen activator inhibitor-1 contributes to the deleterious effect of obesity on the outcome of thrombotic ischemic stroke in mice. J Thromb Haemost. 2007;5:1726–31.
Ritter L, Davidson L, Henry M, Davis-Gorman G, Morrison H, Frye JB, et al. Exaggerated neutrophil-mediated reperfusion injury after ischemic stroke in a rodent model of type 2 diabetes. Microcirculation. 2011;18:552–61.
Terao S, Yilmaz G, Stokes KY, Ishikawa M, Kawase T, Granger DN. Inflammatory and injury responses to ischemic stroke in obese mice. Stroke. 2008;39:943–50.
McColl BW, Rose N, Robson FH, Rothwell NJ, Lawrence CB. Increased brain microvascular MMP-9 and incidence of haemorrhagic transformation in obese mice after experimental stroke. J Cereb Blood Flow Metab. 2010;30:267–72.
Carbone F, La Rocca C, Matarese G. Immunological functions of leptin and adiponectin. Biochimie. 2012;94:2082–8.
Zhang F, Wang S, Signore AP, Chen J. Neuroprotective effects of leptin against ischemic injury induced by oxygen-glucose deprivation and transient cerebral ischemia. Stroke. 2007;38:2329–36.
Langdon KD, Clarke J, Corbett D. Long-term exposure to high fat diet is bad for your brain: exacerbation of focal ischemic brain injury. Neuroscience. 2011;182(C):82–7.
Li W, Prakash R, Chawla D, Du W, Didion SP, Filosa JA, et al. Early effects of high-fat diet on neurovascular function and focal ischemic brain injury. Am J Physiol Regul Integr Comp Physiol. 2013;304:R1001–8.
Kim E, Tolhurst AT, Cho S. Deregulation of inflammatory response in the diabetic condition is associated with increased ischemic brain injury. J Neuroinflammation. 2014;11:83.
Park S, Da Sol K, Kang S, Kwon DY. Ischemic hippocampal cell death induces glucose dysregulation by attenuating glucose-stimulated insulin secretion which is exacerbated by a high fat diet. Life Sci. 2011;88:766–73.
Farooqi IS. Monogenic human obesity. Front Horm Res. 2008;36:1–11.
Mraz M, Haluzik M. The role of adipose tissue immune cells in obesity and low-grade inflammation. J Endocrinol. 2014;222:R113–27.
Santilli F, Vazzana N, Liani R, Guagnano MT, Davì G. Platelet activation in obesity and metabolic syndrome. Obes Rev. 2011;13:27–42.
Denes A, Thornton P, Rothwell NJ, Allan SM. Inflammation and brain injury: acute cerebral ischaemia, peripheral and central inflammation. Brain Behav Immun. 2010;24:708–23.
Osborne KA, Shigeno T, Balarsky AM, Ford I, McCulloch J, Teasdale GM, et al. Quantitative assessment of early brain damage in a rat model of focal cerebral ischaemia. J Neurol Neurosurg Psychiatry. 1987;50:402–10.
Paxinos G, Franklin KBJ. The mouse brain in stereotaxic coordinates. USA: Gulf Professional Publishing; 2004.
Hewitt J, Castilla Guerra L, Fernández-Moreno MDC, Sierra C. Diabetes and stroke prevention: a review. Stroke Res Treat. 2012;2012:673187–6.
Collins VEOA, Donnan GA, Macleod MR, Howells DW. Hypertension and experimental stroke therapies. J Cereb Blood Flow Metab. 2013;33:1141–7.
Dixon JB, O'Brien PE. Obesity and the white blood cell count: changes with sustained weight loss. Obes Surg. 2006;16:251–7.
Guiraudou M, Varlet-Marie E, Raynaud de Mauverger E, Brun J-F. Obesity-related increase in whole blood viscosity includes different profiles according to fat localization. Clin Hemorheol Microcirc. 2013;55:63–73.
Busnelli M, Manzini S, Froio A, Vargiolu A, Cerrito MG, Smolenski RT, et al. Diet induced mild hypercholesterolemia in pigs: local and systemic inflammation, effects on vascular injury - rescue by high-dose statin treatment. PLoS One. 2013;8:e80588.
Hernández GN, Luis C, Rasia ML. Effect of food restriction on hemorheological variables in a rat model of spontaneous hypertriglyceridemic obesity and diabetes. Clin Hemorheol Microcirc. 2004;31:81–7.
Herńandez GN, Dabin C, del C Gayol M, Rasia ML. Haemorheological variables in a rat model of hypertriglyceridaemic obesity and diabetes. Vet Res Commun. 2002;26:625–35.
Asplund K. Randomized clinical trials of hemodilution in acute ischemic stroke. Acta Neurol Scand Suppl. 1989;127:22–30.
Coull BM, Beamer N, de Garmo P, Sexton G, Nordt F, Knox R, et al. Chronic blood hyperviscosity in subjects with acute stroke, transient ischemic attack, and risk factors for stroke. Stroke. 1991;22:162–8.
Wiessner C, Allegrini PR, Ekatodramis D, Jewell UR, Stallmach T, Gassmann M. Increased cerebral infarct volumes in polyglobulic mice overexpressing erythropoietin. J Cereb Blood Flow Metab. 2001;21:857–64.
Fumagalli S, Perego C, Pischiutta F, Zanier ER, De Simoni M-G. The ischemic environment drives microglia and macrophage function. Front Neurol. 2015;6:81.
Wang Q, Xie Z, Zhang W, Zhou J, Wu Y, Zhang M, et al. Myeloperoxidase deletion prevents high-fat diet-induced obesity and insulin resistance. Diabetes. 2014;63:4172–85.
Beray-Berthat V, Croci N, Plotkine M, Margaill I. Polymorphonuclear neutrophils contribute to infarction and oxidative stress in the cortex but not in the striatum after ischemia-reperfusion in rats. Brain Res. 2003;987:32–8.
McColl BW, Rothwell NJ, Allan SM. Systemic inflammatory stimulus potentiates the acute phase and CXC chemokine responses to experimental stroke and exacerbates brain damage via interleukin-1- and neutrophil-dependent mechanisms. J Neurosci. 2007;27:4403–12.
Chapman KZ, Dale VQ, Denes A, Bennett G, Rothwell NJ, Allan SM, et al. A rapid and transient peripheral inflammatory response precedes brain inflammation after experimental stroke. J Cereb Blood Flow Metab. 2009;29:1764–8.
Offner H, Subramanian S, Parker SM, Afentoulis ME, Vandenbark AA, Hurn PD. Experimental stroke induces massive, rapid activation of the peripheral immune system. J Cereb Blood Flow Metab. 2006;26:654–65.
Campbell SJ, Deacon RMJ, Jiang Y, Ferrari C, Pitossi FJ, Anthony DC. Overexpression of IL-1β by adenoviral-mediated gene transfer in the rat brain causes a prolonged hepatic chemokine response, axonal injury and the suppression of spontaneous behaviour. Neurobiol Dis. 2007;27:151–63.
Liu H-B, Tian J, Zhao J-X, Song D-B, Tian J-K. Study on the clinical epidemiological features of acute cerebral stroke inducing systemic inflammatory response syndrome and multiple organ dysfunction syndrome. Zhonghua Liu Xing Bing Xue Za Zhi. 2008;29:294–6.
Yang X-F, He W, Lu W-H, Zeng F-D. Effects of scutellarin on liver function after brain ischemia/reperfusion in rats. Acta Pharmacol Sin. 2003;24:1118–24.
Lawrence CB, Brough D, Knight EM. Obese mice exhibit an altered behavioural and inflammatory response to lipopolysaccharide. Dis Model Mech. 2012;5:649–59.
Ikejima S, Sasaki S, Sashinami H, Mori F, Ogawa Y, Nakamura T, et al. Impairment of host resistance to Listeria monocytogenes infection in liver of db/db and ob/ob mice. Diabetes. 2005;54:182–9.
Hasegawa T, Ito Y, Wijeweera J, Liu J, Malle E, Farhood A, et al. Reduced inflammatory response and increased microcirculatory disturbances during hepatic ischemia-reperfusion injury in steatotic livers of ob/ob mice. Am J Physiol Gastrointest Liver Physiol. 2007;292:G1385–95.