冷暴露对高脂饮食小鼠脂肪棕色化的影响
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摘要
目的观察冷暴露对高脂饮食小鼠脂肪棕色化的影响。方法 8周龄♂C57BL/6J小鼠高脂饮食8周后,随机分为高脂冷暴露组和高脂室温组;同周龄♂C57BL/6J小鼠给予基础饲料喂养8周后,随机分为正常冷暴露组及正常室温组。各组小鼠每天在同一时间段相应温度干预2 h,连续干预8周。检测体质量、进食量、i WAT及BAT重量、血糖、血脂、LEP、ADPN、脂肪组织病理特征,以及UCP1和PHB在i WAT、BAT中原位蛋白表达。结果冷暴露可明显降低高脂饮食小鼠体质量、血糖、i WAT重量/体质量比值、血清中TC、TG、LDL-C及LEP含量,增加进食量及BAT重量/体质量比值; HE染色显示,i WAT和BAT细胞变小且出现多室,i WAT具有棕色化趋势;免疫组化染色显示,i WAT和BAT中UCP1和PHB蛋白表达明显增加。结论冷暴露能对抗高脂饮食造成的体质量增长,其作用可能与激活棕色脂肪组织及诱导脂肪棕色化,增加产热,减少白色脂肪堆积有关。
Aim To observe the effect of cold exposure on browning of white adipose tissues in mice fed with high fat diet. Methods Male 8-week-old C57 BL/6 J mice were randomly divided into HFD + 5 ℃ group and HFD + RT group,after 8 weeks of high-fat diet. Male8-week-old C57 BL/6 J mice were randomly divided into normal + 5 ℃ group and normal + RT group,after 8 weeks of normal diet. Each group of mice were intervened for 2 h at different temperatures in the same time period for 8 weeks. Parameters, including body weight, food intake, inguinal white adipose tissue( i WAT) mass,brown adipose tissue( BAT) mass,blood glucose,blood lipids,leptin,adiponectin,adipose tissue pathology and in situ expression of uncoupling protein 1( UCP1) and prohibitin protein( PHB) in i WAT and BAT. Results Compared with HFD + RT group,cold exposure not only significantly reduced body weight,blood glucose,iW AT weight/body weight ratio,TC,TG,LDL-C and leptin,but also increased food intake and BAT weight in high-fat diet mice. HE staining showed that iW AT and BAT cells became smaller and had multiple compartments. The iW AT had a browning trend. Immunohistochemistry showed that UCP1 and PHB protein in iW AT and BAT significantly increased. Conclusions Cold exposure can counteract the weight gain caused by a high-fat diet,which may be related to the activation of brown adipose tissue and the induction of browning of white adipose tissues,increasing heat production and reducing white fat accumulation.
Aim To observe the effect of cold exposure on browning of white adipose tissues in mice fed with high fat diet. Methods Male 8-week-old C57 BL/6 J mice were randomly divided into HFD + 5 ℃ group and HFD + RT group,after 8 weeks of high-fat diet. Male8-week-old C57 BL/6 J mice were randomly divided into normal + 5 ℃ group and normal + RT group,after 8 weeks of normal diet. Each group of mice were intervened for 2 h at different temperatures in the same time period for 8 weeks. Parameters, including body weight, food intake, inguinal white adipose tissue( i WAT) mass,brown adipose tissue( BAT) mass,blood glucose,blood lipids,leptin,adiponectin,adipose tissue pathology and in situ expression of uncoupling protein 1( UCP1) and prohibitin protein( PHB) in i WAT and BAT. Results Compared with HFD + RT group,cold exposure not only significantly reduced body weight,blood glucose,iW AT weight/body weight ratio,TC,TG,LDL-C and leptin,but also increased food intake and BAT weight in high-fat diet mice. HE staining showed that iW AT and BAT cells became smaller and had multiple compartments. The iW AT had a browning trend. Immunohistochemistry showed that UCP1 and PHB protein in iW AT and BAT significantly increased. Conclusions Cold exposure can counteract the weight gain caused by a high-fat diet,which may be related to the activation of brown adipose tissue and the induction of browning of white adipose tissues,increasing heat production and reducing white fat accumulation.
引文
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[2]Di Cesare M,Bentham J,Stevens G A,et al.Trends in adult body-mass index in 200 countries from 1975 to 2014:a pooled analysis of 1698 population-based measurement studies with 192million participants[J].Lancet,2016,387(10026):1377-96.
[3]Cousin B,Cinti S,Morroni M,et al.Occurrence of brown adipocytes in rat white adipose tissue:molecular and morphological characterization[J].J Cell Sci,1992,103(4):931-42.
[4]Bostr9m P,Wu J,Jedrychowski M P,et al.A PGC1-α-dependent myokine that drives brown-fat-like development of white fat and thermogenesis[J].Nature,2012,481(7382):463-8.
[5]刘芳,高南南,杨润梅,等.不同品系小鼠肥胖模型比较及C57BL/6J小鼠肥胖机制研究[J].中国药理学通报,2013,29(3):360-5.[5]Liu F,Gao N N,Yang R M,et al.Comparison of obesity models established in different strains of mice and mechanism of obese C57BL/6J mice[J].Chin Pharmacol Bull,2013,29(3):360-5.
[6]佘美华,蒋文艳,杨升华,等.新型褪黑素受体激动剂Neu-P11改善慢性睡眠限制大鼠胰岛素敏感性[J].中国药理学通报,2013,29(11):1506-9.[6]She M H,Jiang W Y,Yang S H,et al.Neu-P11,a novel melatonin receptor agonist,improves insulin sensitivity in chronic sleep restricted rats[J].Chin Pharmacol Bull,2013,29(11):1506-9.
[7]Bunyan J,Murrell E A,Shah P P.The induction of obesity in rodents by means of monosodium glutamate[J].Br J Nutr,1976,35(1):25-39.
[8]Cannon B,Nedergaard J.Brown adipose tissue:function and physiological significance[J].Physiol Rev,2004,84(1):277-359.
[9]Lowell B B,Spiegelman B M.Towards a molecular understanding of adaptive thermogenesis[J].Nature,2000,404(6778):652-60.
[10]Orava J,Nuutila P,Lidell M E,et al.Different metabolic responses of human brown adipose tissue to activation by cold and insulin[J].Cell Metab,2011,14(2):272-9.
[11]Artal S M,Tavernarakis N.Prohibitin and mitochondrial biology[J].Trends Endocrinol Metab,2009,20(8):394-401.
[12]Schreiber R,Diwoky C,Schoiswohl G,et al.Cold-induced thermogenesis depends on ATGL-mediated lipolysis in cardiac muscle,but not brown adipose tissue[J].Cell Metab,2017,26(5):753-63.e7.
[13]Bartelt A,Bruns O T,Reimer R,et al.Brown adipose tissue activity controls triglyceride clearance[J].Nat Med,2011,17(2):200-5.
[14]Dodd G T,Decherf S,Loh K,et al.Leptin and insulin act on POMC neurons to promote the browning of white fat[J].Cell,2015,160(1-2):88-104.
[15]Ziemke F,Mantzoros C S.Adiponectin in insulin resistance:lessons from translational research[J].Am J Clin Nutr,2010,91(1):258S-61S.