肥胖相关脂肪因子与高血压的关系
摘要
<正>肥胖状态下,脂肪组织扩增是为了满足能量储存的需求,但造成体质量增加和系统之间平衡被打破。脂肪组织除了有储存三酰甘油的功能外,还有很重要的内分泌功能,脂肪激素在脂肪组织和其他系统之间传递信号,影响全身代谢。Hou等[1]研究结果显示,当人的体质量指数(body mass index, BMI)>25 kg/m2时,会引起代谢紊乱或慢性疾病,例如高血压、高血脂、2型糖尿病及动脉粥样硬化等。世界范围多种族人群研究的结果显示:肥胖人群中,高血压
引文
[1] Hou X, Lu J, Weng J, et al. Impact of waist circumference and body mass index on risk of cardiometabolic disorder and cardiovascular disease in Chinese adults: a national diabetes and metabolic disorders survey[J].PLoS One,2013,8(3):e57319.
[2] Molenaar EA, Hwang SJ, Vasan RS, et al. Burden and rates of treatment and control of cardiovascular disease risk factors in obesity: the Framingham heart study[J].Diabetes Care,2008,31(7):1367-1372.
[3] 徐梦丹, 戴秋艳. 炎症与肥胖相关性高血压研究进展[J].国际心血管病杂志,2015,42(6):372-375.
[4] Kang YS. Obesity associated hypertension: new insights into mechanism[J].Electrolyte Blood Press,2013,11(2):46-52.
[5] Seven E, Husemoen LL, Wachtell K, et al. Overweight, adipocytokines and hypertension: a prospective population-based study[J].J Hypertens,2014,32(7):1488-1494.
[6] Ohashi K, Ouchi N, Matsuzawa Y. Adiponectin and hypertension[J].Am J Hypertens,2011,24(3):263-269.
[7] Rahmouni K, Morgan DA, Morgan GM, et al. Role of selective leptin resistance in diet-induced obesity hypertension[J].Diabetes,2005,54(7):2012-2018.
[8] Goossens GH, McQuaid SE, Dennis AL, et al. Angiotensin Ⅱ: a major regulator of subcutaneous adipose tissue blood flow in humans[J].J Physiol,2006,571(Pt 2):451-460.
[9] Ye J, Gao Z, Yin J, et al. Hypoxia is a potential risk factor for chronic inflammation and adiponectin reduction in adipose tissue of ob/ob and dietary obese mice[J].Am J Physiol Endocrinol Metab,2007,293:E1118-E1128.
[10] Yin J, Gao Z, He Q, et al. Role of hypoxia in obesity-induced disorders of glucose and lipid metabolism in adipose tissue[J].Am J Physiol Endocrinol Metab,2009,296:E333-E342.
[11] Ye J. Emerging role of adipose tissue hypoxia in obesity and insulin resistance[J].Int J Obes,2009,33(1):54-66.
[12] Wang H, Ye J. Regulation of energy balance by inflammation: common theme in physiology and pathology[J].Rev Endocr Metab Disord,2015,16(1):47-54.
[13] Lee Yun S, Kim Jw, Osborne O, et al. Increased adipocyte O2 consumption triggers HIF-1α, causing inflammation and insulin resistance in obesity[J].Cell,2014,157(6):1339-1352.
[14] Goossens GH, Blaak EE. Adipose tissue dysfunction and impaired metabolic health in human obesity: a matter of oxygen?[J].Front Endocrinol(Lausanne),2015,6:55.
[15] Frayn KN, Karpe F. Regulation of human subcutaneous adipose tissue blood flow[J].Int J Obes (Lond),2014,38(8):1019-26.
[16] Ye J, McGuinness OP. Inflammation during obesity is not all bad: evidence from animal and human studies[J].Am J Physiol Endocrinol Metab,2013,304(5):E466-E477.
[17] Wernstedt AI, Tao C, Morley TS, et al. Adipocyte inflammation is essential for healthy adipose tissue expansion and remodeling[J].Cell Metabolism,2014,20(1):103-118.
[18] Lee JH, Zhang Y, Zhao Z, et al. Intracellular ATP in balance of pro- and anti-inflammatory cytokines in adipose tissue with and without tissue expansion[J].Int J Obes (Lond),2017,41(4):645-651.
[19] Myers MG, Jr., Heymsfield SB, Haft C, et al. Challenges and opportunities of defining clinical leptin resistance[J].Cell Metab,2012,15(2):150-156.
[20] Rosenbaum M, Leibel RL. The role of leptin in human physiology[J].N Engl J Med,1999,341(12):913-915.
[21] Konner AC, Bruning JC. Selective insulin and leptin resistance in metabolic disorders[J].Cell Metab,2012,16(2):144-152.
[22] Hao Z, Munzberg H, Rezai-Zadeh K, et al. Leptin deficient ob/ob mice and diet-induced obese mice responded differently to Roux-en-Y bypass surgery[J].Int J Obes(Lond),2015,39(5):798-805.
[23] Dodd GT, 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.
[24] Zeng W, Pirzgalska RM, Pereira MM, et al. Sympathetic neuro-adipose connections mediate leptin-driven lipolysis[J].Cell,2015,163(1):84-94.
[25] Wu J, Bostrom P, Sparks LM, et al. Beige adipocytes are a distinct type of thermogenic fat cell in mouse and human[J].Cell,2012,150(2):366-376.
[26] Harms M, Seale P. Brown and beige fat: development, function and therapeutic potential[J].Nat Med,2013,19(10):1252-1263.
[27] Kotsis V, Nilsson P, Grassi G, et al. New developments in the pathogenesis of obesity-induced hypertension[J].J Hypertens,2015,33(8):1499-1508.
[28] Mark AL, Shaffer RA, Correia ML, et al. Contrasting blood pressure effects of obesity in leptin-deficient ob/ob mice and agouti yellow obese mice[J].J Hypertens,1999,17(12 Pt 2):1949-1953.
[29] Albarado DC, McClaine J, Stephens JM, et al. Impaired coordination of nutrient intake and substrate oxidation in melanocortin-4 receptor knockout mice[J].Endocrinology,2004,145(1):243-252.
[30] Sutton GM, Trevaskis JL, Hulver MW, et al. Diet-genotype interactions in the development of the obese, insulin-resistant phenotype of C57BL/6J mice lacking melanocortin-3 or -4 receptors[J].Endocrinology,2006,147(5):2183-2196.
[31] Tallam LS, Stec DE, Willis MA, et al. Melanocortin-4 receptor-deficient mice are not hypertensive or salt-sensitive despite obesity, hyperinsulinemia, and hyperleptinemia[J].Hypertension,2005,46(2):326-332.
[32] Farooqi IS, Keogh JM, Yeo GS, et al. Clinical spectrum of obesity and mutations in the melanocortin 4 receptor gene[J].N Engl J Med,2003,348(12):1085-1095.
[33] Abella V, Scotece M, Conde J, et al. Leptin in the interplay of inflammation, metabolism and immune system disorders[J].Nat Rev Rheumatol,2017,13(2):100-109.
[34] Ye J, Keller J. Regulation of energy metabolism by inflammation: a feedback response in obesity and calorie restriction[J].Aging,2010,2(6):361-368.
[35] Shek EW, Brands MW, Hall JE. Chronic leptin infusion increases arterial pressure[J].Hypertension,1998,31(1 Pt 2):409-414.
[36] Simonds SE, Pryor JT, Ravussin E, et al. Leptin mediates the increase in blood pressure associated with obesity[J].Cell,2014,159(6):1404-1416.
[37] Brown RJ, Meehan CA, Gorden P. Leptin does not mediate hypertension associated with human obesity[J].Cell,2015,162(3):465-466.
[38] Solak Y, Afsar B, Vaziri ND, et al. Hypertension as an autoimmune and inflammatory disease[J].Hypertens Res,2016,39(8):567-573.
[39] Goldberg RB. Cytokine and cytokine-like inflammation markers, endothelial dysfunction, and imbalanced coagulation in development of diabetes and its complications[J].J Clin Endocrinol Metab,2009,94(9):3171-3182.
[40] Kotas ME, Medzhitov R. Homeostasis, inflammation, and disease susceptibility[J].Cell,2015,160(5):816-827.
[41] Ke B, Zhao Z, Ye X, et al. Inactivation of NF-kappaB p65 (RelA) in liver improved insulin sensitivity and inhibited cAMP/PKA pathway[J].Diabetes,2015,64(10):3355-3362.
[42] Sheng L, Zhou Y, Chen Z, et al. NF-kappaB-inducing kinase (NIK) promotes hyperglycemia and glucose intolerance in obesity by augmenting glucagon action[J].Nat Med,2012,18(6):943-949.
[43] Caillon A, Schiffrin EL. Role of inflammation and immunity in hypertension: recent epidemiological, laboratory, and clinical evidence[J].Curr Hypertens Rep,2016,18(3):21.
[44] 关亚群,王延蛟,孙丽丽,等. 脂肪组织内脂素、脂联素的表达与代谢综合征[J].中华高血压杂志,2009,17(11):980-982.
[45] Kim DH, Kim C, Ding EL, et al. Adiponectin levels and the risk of hypertension: a systematic review and meta-analysis[J].Hypertension,2013,62(1):27-32.
[46] Iwashima Y, Katsuya T, Ishikawa K, et al. Hypoadiponectinemia is an independent risk factor for hypertension[J].Hypertension,2004,43(6):1318-23.
[47] Ohashi K, Kihara S, Ouchi N, et al. Adiponectin replenishment ameliorates obesity-related hypertension[J].Hypertension,2006,47(6):1108-1116.
[48] Asferg C, Mogelvang R, Flyvbjerg A, et al. Leptin, not adiponectin, predicts hypertension in the Copenhagen city heart study[J].Am J Hypertens,2010,23(3):327-333.
[49] Margaritis M, Antonopoulos AS, Digby J, et al. Interactions between vascular wall and perivascular adipose tissue reveal novel roles for adiponectin in the regulation of endothelial nitric oxide synthase function in human vessels[J].Circulation,2013,127(22):2209-2221.
[50] Du Y, Li R, Lau WB, et al. Adiponectin at physiologically relevant concentrations enhances the vasorelaxative effect of acetylcholine via Cav-1/AdipoR-1 signaling[J].PLoS One,2016,11(3):e0152247.
[51] Goldstein BJ, Scalia RG, Ma XL. Protective vascular and myocardial effects of adiponectin[J].Nat Clin Pract Cardiovasc Med,2009,6(1):27-35.
[52] Qiao L, Kinney B, Schaack J, et al. Adiponectin inhibits lipolysis in mouse adipocytes[J].Diabetes,2011,60(5):1519-1527.
[53] Okada-Iwabu M, Yamauchi T, Iwabu M, et al. A small-molecule AdipoR agonist for type 2 diabetes and short life in obesity[J].Nature,2013,503(7477):493-499.
[54] 李昊,王亚萍,宋艳,等.高脂喂食诱导的肥胖大鼠肾周脂肪功能与肾损害的关系及替米沙坦干预的影响[J].中华高血压杂志,2015,23(11):1053-1061.
[55] 刘蕾,殷艳蓉,宋艳,等.血管周围脂肪组织源瘦素促进高脂喂食诱导的肥胖大鼠血管平滑肌细胞增殖[J].中华高血压杂志,2017,25(3):272-279.
[2] Molenaar EA, Hwang SJ, Vasan RS, et al. Burden and rates of treatment and control of cardiovascular disease risk factors in obesity: the Framingham heart study[J].Diabetes Care,2008,31(7):1367-1372.
[3] 徐梦丹, 戴秋艳. 炎症与肥胖相关性高血压研究进展[J].国际心血管病杂志,2015,42(6):372-375.
[4] Kang YS. Obesity associated hypertension: new insights into mechanism[J].Electrolyte Blood Press,2013,11(2):46-52.
[5] Seven E, Husemoen LL, Wachtell K, et al. Overweight, adipocytokines and hypertension: a prospective population-based study[J].J Hypertens,2014,32(7):1488-1494.
[6] Ohashi K, Ouchi N, Matsuzawa Y. Adiponectin and hypertension[J].Am J Hypertens,2011,24(3):263-269.
[7] Rahmouni K, Morgan DA, Morgan GM, et al. Role of selective leptin resistance in diet-induced obesity hypertension[J].Diabetes,2005,54(7):2012-2018.
[8] Goossens GH, McQuaid SE, Dennis AL, et al. Angiotensin Ⅱ: a major regulator of subcutaneous adipose tissue blood flow in humans[J].J Physiol,2006,571(Pt 2):451-460.
[9] Ye J, Gao Z, Yin J, et al. Hypoxia is a potential risk factor for chronic inflammation and adiponectin reduction in adipose tissue of ob/ob and dietary obese mice[J].Am J Physiol Endocrinol Metab,2007,293:E1118-E1128.
[10] Yin J, Gao Z, He Q, et al. Role of hypoxia in obesity-induced disorders of glucose and lipid metabolism in adipose tissue[J].Am J Physiol Endocrinol Metab,2009,296:E333-E342.
[11] Ye J. Emerging role of adipose tissue hypoxia in obesity and insulin resistance[J].Int J Obes,2009,33(1):54-66.
[12] Wang H, Ye J. Regulation of energy balance by inflammation: common theme in physiology and pathology[J].Rev Endocr Metab Disord,2015,16(1):47-54.
[13] Lee Yun S, Kim Jw, Osborne O, et al. Increased adipocyte O2 consumption triggers HIF-1α, causing inflammation and insulin resistance in obesity[J].Cell,2014,157(6):1339-1352.
[14] Goossens GH, Blaak EE. Adipose tissue dysfunction and impaired metabolic health in human obesity: a matter of oxygen?[J].Front Endocrinol(Lausanne),2015,6:55.
[15] Frayn KN, Karpe F. Regulation of human subcutaneous adipose tissue blood flow[J].Int J Obes (Lond),2014,38(8):1019-26.
[16] Ye J, McGuinness OP. Inflammation during obesity is not all bad: evidence from animal and human studies[J].Am J Physiol Endocrinol Metab,2013,304(5):E466-E477.
[17] Wernstedt AI, Tao C, Morley TS, et al. Adipocyte inflammation is essential for healthy adipose tissue expansion and remodeling[J].Cell Metabolism,2014,20(1):103-118.
[18] Lee JH, Zhang Y, Zhao Z, et al. Intracellular ATP in balance of pro- and anti-inflammatory cytokines in adipose tissue with and without tissue expansion[J].Int J Obes (Lond),2017,41(4):645-651.
[19] Myers MG, Jr., Heymsfield SB, Haft C, et al. Challenges and opportunities of defining clinical leptin resistance[J].Cell Metab,2012,15(2):150-156.
[20] Rosenbaum M, Leibel RL. The role of leptin in human physiology[J].N Engl J Med,1999,341(12):913-915.
[21] Konner AC, Bruning JC. Selective insulin and leptin resistance in metabolic disorders[J].Cell Metab,2012,16(2):144-152.
[22] Hao Z, Munzberg H, Rezai-Zadeh K, et al. Leptin deficient ob/ob mice and diet-induced obese mice responded differently to Roux-en-Y bypass surgery[J].Int J Obes(Lond),2015,39(5):798-805.
[23] Dodd GT, 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.
[24] Zeng W, Pirzgalska RM, Pereira MM, et al. Sympathetic neuro-adipose connections mediate leptin-driven lipolysis[J].Cell,2015,163(1):84-94.
[25] Wu J, Bostrom P, Sparks LM, et al. Beige adipocytes are a distinct type of thermogenic fat cell in mouse and human[J].Cell,2012,150(2):366-376.
[26] Harms M, Seale P. Brown and beige fat: development, function and therapeutic potential[J].Nat Med,2013,19(10):1252-1263.
[27] Kotsis V, Nilsson P, Grassi G, et al. New developments in the pathogenesis of obesity-induced hypertension[J].J Hypertens,2015,33(8):1499-1508.
[28] Mark AL, Shaffer RA, Correia ML, et al. Contrasting blood pressure effects of obesity in leptin-deficient ob/ob mice and agouti yellow obese mice[J].J Hypertens,1999,17(12 Pt 2):1949-1953.
[29] Albarado DC, McClaine J, Stephens JM, et al. Impaired coordination of nutrient intake and substrate oxidation in melanocortin-4 receptor knockout mice[J].Endocrinology,2004,145(1):243-252.
[30] Sutton GM, Trevaskis JL, Hulver MW, et al. Diet-genotype interactions in the development of the obese, insulin-resistant phenotype of C57BL/6J mice lacking melanocortin-3 or -4 receptors[J].Endocrinology,2006,147(5):2183-2196.
[31] Tallam LS, Stec DE, Willis MA, et al. Melanocortin-4 receptor-deficient mice are not hypertensive or salt-sensitive despite obesity, hyperinsulinemia, and hyperleptinemia[J].Hypertension,2005,46(2):326-332.
[32] Farooqi IS, Keogh JM, Yeo GS, et al. Clinical spectrum of obesity and mutations in the melanocortin 4 receptor gene[J].N Engl J Med,2003,348(12):1085-1095.
[33] Abella V, Scotece M, Conde J, et al. Leptin in the interplay of inflammation, metabolism and immune system disorders[J].Nat Rev Rheumatol,2017,13(2):100-109.
[34] Ye J, Keller J. Regulation of energy metabolism by inflammation: a feedback response in obesity and calorie restriction[J].Aging,2010,2(6):361-368.
[35] Shek EW, Brands MW, Hall JE. Chronic leptin infusion increases arterial pressure[J].Hypertension,1998,31(1 Pt 2):409-414.
[36] Simonds SE, Pryor JT, Ravussin E, et al. Leptin mediates the increase in blood pressure associated with obesity[J].Cell,2014,159(6):1404-1416.
[37] Brown RJ, Meehan CA, Gorden P. Leptin does not mediate hypertension associated with human obesity[J].Cell,2015,162(3):465-466.
[38] Solak Y, Afsar B, Vaziri ND, et al. Hypertension as an autoimmune and inflammatory disease[J].Hypertens Res,2016,39(8):567-573.
[39] Goldberg RB. Cytokine and cytokine-like inflammation markers, endothelial dysfunction, and imbalanced coagulation in development of diabetes and its complications[J].J Clin Endocrinol Metab,2009,94(9):3171-3182.
[40] Kotas ME, Medzhitov R. Homeostasis, inflammation, and disease susceptibility[J].Cell,2015,160(5):816-827.
[41] Ke B, Zhao Z, Ye X, et al. Inactivation of NF-kappaB p65 (RelA) in liver improved insulin sensitivity and inhibited cAMP/PKA pathway[J].Diabetes,2015,64(10):3355-3362.
[42] Sheng L, Zhou Y, Chen Z, et al. NF-kappaB-inducing kinase (NIK) promotes hyperglycemia and glucose intolerance in obesity by augmenting glucagon action[J].Nat Med,2012,18(6):943-949.
[43] Caillon A, Schiffrin EL. Role of inflammation and immunity in hypertension: recent epidemiological, laboratory, and clinical evidence[J].Curr Hypertens Rep,2016,18(3):21.
[44] 关亚群,王延蛟,孙丽丽,等. 脂肪组织内脂素、脂联素的表达与代谢综合征[J].中华高血压杂志,2009,17(11):980-982.
[45] Kim DH, Kim C, Ding EL, et al. Adiponectin levels and the risk of hypertension: a systematic review and meta-analysis[J].Hypertension,2013,62(1):27-32.
[46] Iwashima Y, Katsuya T, Ishikawa K, et al. Hypoadiponectinemia is an independent risk factor for hypertension[J].Hypertension,2004,43(6):1318-23.
[47] Ohashi K, Kihara S, Ouchi N, et al. Adiponectin replenishment ameliorates obesity-related hypertension[J].Hypertension,2006,47(6):1108-1116.
[48] Asferg C, Mogelvang R, Flyvbjerg A, et al. Leptin, not adiponectin, predicts hypertension in the Copenhagen city heart study[J].Am J Hypertens,2010,23(3):327-333.
[49] Margaritis M, Antonopoulos AS, Digby J, et al. Interactions between vascular wall and perivascular adipose tissue reveal novel roles for adiponectin in the regulation of endothelial nitric oxide synthase function in human vessels[J].Circulation,2013,127(22):2209-2221.
[50] Du Y, Li R, Lau WB, et al. Adiponectin at physiologically relevant concentrations enhances the vasorelaxative effect of acetylcholine via Cav-1/AdipoR-1 signaling[J].PLoS One,2016,11(3):e0152247.
[51] Goldstein BJ, Scalia RG, Ma XL. Protective vascular and myocardial effects of adiponectin[J].Nat Clin Pract Cardiovasc Med,2009,6(1):27-35.
[52] Qiao L, Kinney B, Schaack J, et al. Adiponectin inhibits lipolysis in mouse adipocytes[J].Diabetes,2011,60(5):1519-1527.
[53] Okada-Iwabu M, Yamauchi T, Iwabu M, et al. A small-molecule AdipoR agonist for type 2 diabetes and short life in obesity[J].Nature,2013,503(7477):493-499.
[54] 李昊,王亚萍,宋艳,等.高脂喂食诱导的肥胖大鼠肾周脂肪功能与肾损害的关系及替米沙坦干预的影响[J].中华高血压杂志,2015,23(11):1053-1061.
[55] 刘蕾,殷艳蓉,宋艳,等.血管周围脂肪组织源瘦素促进高脂喂食诱导的肥胖大鼠血管平滑肌细胞增殖[J].中华高血压杂志,2017,25(3):272-279.