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Erschienen in: Current Hypertension Reports 3/2013

01.06.2013 | Hypertension and Obesity (E Reisin, Section Editor)

Animal Models in Obesity and Hypertension

verfasst von: Gabriella Segal-Lieberman, Talma Rosenthal

Erschienen in: Current Hypertension Reports | Ausgabe 3/2013

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Abstract

Although obesity is a well-known risk factor for hypertension, the mechanisms by which hypertension develops in obese patients are not entirely clear. Animal models of obesity and their different susceptibilities to develop hypertension have revealed some of the mechanisms linking obesity and hypertension. Adipose tissue is an endocrine organ secreting hormones that impact blood pressure, such as elements of the renin-angiotensin system whose role in hypertension have been established. In addition, the appetite-suppressing adipokine leptin activates the sympathetic nervous system via the melanocortin system, and this activation, especially in the kidney, increases blood pressure. Leptin secretion from adipocytes is increased in most models of obesity due to leptin resistance, although the resistance is often selective to the anorexigenic effect, while the susceptibility to the hypertensive effect remains intact. Understanding the pathways by which obesity contributes to increased blood pressure will hopefully pave the way to and better define the appropriate treatment for obesity-induced hypertension.
Literatur
1.
Zurück zum Zitat Reisin E, Jack AV. Obesity and hypertension: mechanisms, cardio-renal consequences, and therapeutic approaches. Med Clin North Am. 2009;93:733–51.PubMedCrossRef Reisin E, Jack AV. Obesity and hypertension: mechanisms, cardio-renal consequences, and therapeutic approaches. Med Clin North Am. 2009;93:733–51.PubMedCrossRef
2.
Zurück zum Zitat Owen J, Reisin E. Non-communicable disease: a welcome and long needed addition to the WHO’s 2012 World Health Statistics. Curr Hypertens Rep. 2012;14:475–7.PubMedCrossRef Owen J, Reisin E. Non-communicable disease: a welcome and long needed addition to the WHO’s 2012 World Health Statistics. Curr Hypertens Rep. 2012;14:475–7.PubMedCrossRef
3.
Zurück zum Zitat Zhao M, Li Y, Wang J, Ebihara K, et al. Azilsartan treatment improves insulin sensitivity in obese spontaneously hypertensive Koletsky rats. Diabetes Obes Metab. 2011;13:1123–9.PubMedCrossRef Zhao M, Li Y, Wang J, Ebihara K, et al. Azilsartan treatment improves insulin sensitivity in obese spontaneously hypertensive Koletsky rats. Diabetes Obes Metab. 2011;13:1123–9.PubMedCrossRef
4.
Zurück zum Zitat Jenkins NT, Padilla J, Arce-Esquivel AA, et al. Effects of endurance exercise training, metformin, and their combination on adipose tissue leptin and IL-10 secretion in OLETF rats. J Appl Physiol. 2012;113:1873–83.PubMedCrossRef Jenkins NT, Padilla J, Arce-Esquivel AA, et al. Effects of endurance exercise training, metformin, and their combination on adipose tissue leptin and IL-10 secretion in OLETF rats. J Appl Physiol. 2012;113:1873–83.PubMedCrossRef
5.
Zurück zum Zitat Chen B, Moore A, Escobedo LV, et al. Sitagliptin lowers glucagon and improves glucose tolerance in prediabetic obese SHROB rats. Exp Biol Med (Maywood). 2011;236:309–14.CrossRef Chen B, Moore A, Escobedo LV, et al. Sitagliptin lowers glucagon and improves glucose tolerance in prediabetic obese SHROB rats. Exp Biol Med (Maywood). 2011;236:309–14.CrossRef
7.
Zurück zum Zitat Perfield 2nd JW, Ortinau LC, Pickering RT, et al. Altered hepatic lipid metabolism contributes to nonalcoholic Fatty liver disease in leptin-deficient ob/ob mice. J Obes. 2013;2013:296537. doi:10.1155/2013/296537. Epub 2013 Jan 16.PubMed Perfield 2nd JW, Ortinau LC, Pickering RT, et al. Altered hepatic lipid metabolism contributes to nonalcoholic Fatty liver disease in leptin-deficient ob/ob mice. J Obes. 2013;2013:296537. doi:10.​1155/​2013/​296537. Epub 2013 Jan 16.PubMed
9.
Zurück zum Zitat Rahmouni K. Leptin-induced sympathetic nerve activation: signaling mechanisms and cardiovascular consequences in obesity. Curr Hypertens Rev. 2010;6:104–209.PubMedCrossRef Rahmouni K. Leptin-induced sympathetic nerve activation: signaling mechanisms and cardiovascular consequences in obesity. Curr Hypertens Rev. 2010;6:104–209.PubMedCrossRef
10.
Zurück zum Zitat Ketonen J, Shi J, Martonen E, Mervaala E. Periadventitial adipose tissue promotes endothelial dysfunction via oxidative stress in diet-induced obese C57Bl/6 mice. Circ J. 2010;74:1479–87.PubMedCrossRef Ketonen J, Shi J, Martonen E, Mervaala E. Periadventitial adipose tissue promotes endothelial dysfunction via oxidative stress in diet-induced obese C57Bl/6 mice. Circ J. 2010;74:1479–87.PubMedCrossRef
11.
Zurück zum Zitat • Hilzendeger AM, Morgan DA, Brooks L, et al. A brain leptin-renin angiotensin system interaction in the regulation of sympathetic nerve activity. Am J Physiol Heart Circ Physiol. 2012;303:H197–206. Intracerebroventricular losartan inhibited renal and brown adipose tissue (BAT), captopril attenuated leptin effect on renal and BAT SNA, while intracerebrovascular leptin in rats induced upregulation of brain RAS. All these indicate a brain leptin-RAS interaction.PubMedCrossRef • Hilzendeger AM, Morgan DA, Brooks L, et al. A brain leptin-renin angiotensin system interaction in the regulation of sympathetic nerve activity. Am J Physiol Heart Circ Physiol. 2012;303:H197–206. Intracerebroventricular losartan inhibited renal and brown adipose tissue (BAT), captopril attenuated leptin effect on renal and BAT SNA, while intracerebrovascular leptin in rats induced upregulation of brain RAS. All these indicate a brain leptin-RAS interaction.PubMedCrossRef
12.
Zurück zum Zitat • do Carmo JM, da Silva AA, Rushing JS, Hall JE. Activation of the central melanocortin system contributes to the increased arterial pressure in obese Zucker rats. Am J Physiol Regul Integr Comp Physiol. 2012;302:R561–7. A functioning melanocortin system is critical in mediating the ability of leptin to induce hypertension, and its activation can lead to an increase in blood pressure in the absence of leptin.PubMedCrossRef • do Carmo JM, da Silva AA, Rushing JS, Hall JE. Activation of the central melanocortin system contributes to the increased arterial pressure in obese Zucker rats. Am J Physiol Regul Integr Comp Physiol. 2012;302:R561–7. A functioning melanocortin system is critical in mediating the ability of leptin to induce hypertension, and its activation can lead to an increase in blood pressure in the absence of leptin.PubMedCrossRef
13.
Zurück zum Zitat Hall JE, da Silva AA. do Carmo JM, et al. Obesity-induced hypertension: role of sympathetic nervous system, leptin, and melanocortins. J Biol Chem. 2010;285:17271–6.PubMedCrossRef Hall JE, da Silva AA. do Carmo JM, et al. Obesity-induced hypertension: role of sympathetic nervous system, leptin, and melanocortins. J Biol Chem. 2010;285:17271–6.PubMedCrossRef
14.
Zurück zum Zitat Marc Y, Llorens-Cortes C. The role of the brain renin-angiotensin system in hypertension: implications for new treatment. Prog Neurobiol. 2011;95:89–103.PubMedCrossRef Marc Y, Llorens-Cortes C. The role of the brain renin-angiotensin system in hypertension: implications for new treatment. Prog Neurobiol. 2011;95:89–103.PubMedCrossRef
15.
Zurück zum Zitat Grobe JL, Grobe CL, Beltz TG, et al. The brain renin-angiotensin system controls divergent efferent mechanisms to regulate fluid and energy balance. Cell Metab. 2010;12:431–42.PubMedCrossRef Grobe JL, Grobe CL, Beltz TG, et al. The brain renin-angiotensin system controls divergent efferent mechanisms to regulate fluid and energy balance. Cell Metab. 2010;12:431–42.PubMedCrossRef
16.
Zurück zum Zitat Goncalves AC, Tank J, Diedrich A, et al. Diabetic hypertensive leptin receptor-deficient db/db mice develop cardioregulatory autonomic dysfunction. Hypertension. 2009;53:387–92.PubMedCrossRef Goncalves AC, Tank J, Diedrich A, et al. Diabetic hypertensive leptin receptor-deficient db/db mice develop cardioregulatory autonomic dysfunction. Hypertension. 2009;53:387–92.PubMedCrossRef
17.
Zurück zum Zitat Dubinion JH, da Silva AA, Hall JE. Chronic blood pressure and appetite responses to central leptin infusion in rats fed a high fat diet. J Hypertens. 2011;29:758–62.PubMedCrossRef Dubinion JH, da Silva AA, Hall JE. Chronic blood pressure and appetite responses to central leptin infusion in rats fed a high fat diet. J Hypertens. 2011;29:758–62.PubMedCrossRef
18.
Zurück zum Zitat da Silva AA, Carmo JM, Hall JE. Role of leptin and central nervous system melanocortins in obesity hypertension. Curr Opin Nephrol Hypertens. 2013;22:135–40.PubMedCrossRef da Silva AA, Carmo JM, Hall JE. Role of leptin and central nervous system melanocortins in obesity hypertension. Curr Opin Nephrol Hypertens. 2013;22:135–40.PubMedCrossRef
19.
Zurück zum Zitat Segal-Lieberman G, Bradley RL, Kokkotou E, et al. Melanin-concentrating hormone is a critical mediator of the leptin-deficient phenotype. Proc Natl Acad Sci USA. 2003;100:10085–90.PubMedCrossRef Segal-Lieberman G, Bradley RL, Kokkotou E, et al. Melanin-concentrating hormone is a critical mediator of the leptin-deficient phenotype. Proc Natl Acad Sci USA. 2003;100:10085–90.PubMedCrossRef
20.
Zurück zum Zitat Pissios P. Animals models of MCH function and what they can tell us about its role in energy balance. Peptides. 2009;30:2040–4.PubMedCrossRef Pissios P. Animals models of MCH function and what they can tell us about its role in energy balance. Peptides. 2009;30:2040–4.PubMedCrossRef
21.
Zurück zum Zitat Xiong XQ, Chen WW, Han Y, et al. Enhanced adipose afferent reflex contributes to sympathetic activation in diet-induced obesity hypertension. Hypertension. 2012;60:1280–6.PubMedCrossRef Xiong XQ, Chen WW, Han Y, et al. Enhanced adipose afferent reflex contributes to sympathetic activation in diet-induced obesity hypertension. Hypertension. 2012;60:1280–6.PubMedCrossRef
22.
Zurück zum Zitat Li P, Cui BP, Zhang LL, et al. Melanocortin 3/4 receptors in paraventricular nucleus modulate sympathetic outflow and blood pressure. Exp Physiol. 2013;98:435–43.PubMedCrossRef Li P, Cui BP, Zhang LL, et al. Melanocortin 3/4 receptors in paraventricular nucleus modulate sympathetic outflow and blood pressure. Exp Physiol. 2013;98:435–43.PubMedCrossRef
23.
Zurück zum Zitat do Carmo JM, da Silva AA, Cai Z, et al. Control of blood pressure, appetite, and glucose by leptin in mice lacking leptin receptors in proopiomelanocortin neurons. Hypertension. 2011;57:918–26.PubMedCrossRef do Carmo JM, da Silva AA, Cai Z, et al. Control of blood pressure, appetite, and glucose by leptin in mice lacking leptin receptors in proopiomelanocortin neurons. Hypertension. 2011;57:918–26.PubMedCrossRef
24.
Zurück zum Zitat Kievit P, Halem H, Marks DL. Chronic treatment with a melanocortin-4 receptor agonist causes weight loss, reduces insulin resistance, and improves cardiovascular function in diet-induced obese rhesus macaques. Diabetes. 2013;62:490–7.PubMedCrossRef Kievit P, Halem H, Marks DL. Chronic treatment with a melanocortin-4 receptor agonist causes weight loss, reduces insulin resistance, and improves cardiovascular function in diet-induced obese rhesus macaques. Diabetes. 2013;62:490–7.PubMedCrossRef
25.
Zurück zum Zitat Li W, Peng H, Seth DM, Feng Y. The prorenin and (pro)renin receptor: new players in the brain renin-angiotensin system? Int J Hypertens. 2012;2012:290635.PubMed Li W, Peng H, Seth DM, Feng Y. The prorenin and (pro)renin receptor: new players in the brain renin-angiotensin system? Int J Hypertens. 2012;2012:290635.PubMed
26.
Zurück zum Zitat Sigmund CD. Divergent mechanism regulating fluid intake and metabolism by the brain renin-angiotensin system. Am J Physiol Regul Integr Comp Physiol. 2012;302:R313–20.PubMedCrossRef Sigmund CD. Divergent mechanism regulating fluid intake and metabolism by the brain renin-angiotensin system. Am J Physiol Regul Integr Comp Physiol. 2012;302:R313–20.PubMedCrossRef
27.
Zurück zum Zitat Yiannikouris F, Karounos M, Charnigo R, et al. Adipocyte-specific deficiency of angiotensinogen decreases plasma angiotensinogen concentration and systolic blood pressure in mice. Am J Physiol Regul Integr Comp Physiol. 2012;302:R244–51.PubMedCrossRef Yiannikouris F, Karounos M, Charnigo R, et al. Adipocyte-specific deficiency of angiotensinogen decreases plasma angiotensinogen concentration and systolic blood pressure in mice. Am J Physiol Regul Integr Comp Physiol. 2012;302:R244–51.PubMedCrossRef
28.
Zurück zum Zitat • Briones AM, Nguyen Dinh Cat A, Callera GE, et al. Adipocytes produce aldosterone through calcineurin-dependent signaling pathways: implications in diabetes mellitus-associated obesity and vascular dysfunction. Hypertension. 2012;59:1069–78. Functional adipocyte-derived aldosterone regulates adipocyte differentiation and vascular function in an autocrine and paracrine manner, respectively. These novel findings identify adipocytes (obtained from obese diabetic db/db) as a putative link between aldosterone and vascular dysfunction in diabetes mellitus-associated obesity.PubMedCrossRef • Briones AM, Nguyen Dinh Cat A, Callera GE, et al. Adipocytes produce aldosterone through calcineurin-dependent signaling pathways: implications in diabetes mellitus-associated obesity and vascular dysfunction. Hypertension. 2012;59:1069–78. Functional adipocyte-derived aldosterone regulates adipocyte differentiation and vascular function in an autocrine and paracrine manner, respectively. These novel findings identify adipocytes (obtained from obese diabetic db/db) as a putative link between aldosterone and vascular dysfunction in diabetes mellitus-associated obesity.PubMedCrossRef
29.
Zurück zum Zitat • Nguyen Dinh Cat A, Briones AM, Callera GE, et al. Adipocyte-derived factors regulate vascular smooth muscle cells through mineralocorticoid and glucocorticoid receptors. Hypertension. 2011;58:479–88. Adipocyte-derived factor regulates vsmc function through MAPK, indicating crosstalk between adipocytes and smooth muscle cells.PubMedCrossRef • Nguyen Dinh Cat A, Briones AM, Callera GE, et al. Adipocyte-derived factors regulate vascular smooth muscle cells through mineralocorticoid and glucocorticoid receptors. Hypertension. 2011;58:479–88. Adipocyte-derived factor regulates vsmc function through MAPK, indicating crosstalk between adipocytes and smooth muscle cells.PubMedCrossRef
30.
Zurück zum Zitat Yamashiro T, Kuge H, Zhang J, Honke K. Calcineurin mediates the angiotensin II-induced aldosterone synthesis in the adrenal glands by up-regulation of transcription of the CYP11B2 gene. J Biochem. 2010;148:115–23.PubMedCrossRef Yamashiro T, Kuge H, Zhang J, Honke K. Calcineurin mediates the angiotensin II-induced aldosterone synthesis in the adrenal glands by up-regulation of transcription of the CYP11B2 gene. J Biochem. 2010;148:115–23.PubMedCrossRef
31.
Zurück zum Zitat • Yiannikouris F, Gupte M, Putnam K, et al. Adipocyte deficiency of angiotensinogen prevents obesity-induced hypertension in male mice. Hypertension. 2012;60:1524–30. Results suggest that adipose tissue serves as a major source of angiotensin II in the development of hypertension.PubMedCrossRef • Yiannikouris F, Gupte M, Putnam K, et al. Adipocyte deficiency of angiotensinogen prevents obesity-induced hypertension in male mice. Hypertension. 2012;60:1524–30. Results suggest that adipose tissue serves as a major source of angiotensin II in the development of hypertension.PubMedCrossRef
32.
Zurück zum Zitat Northcott CA, Fink GD, Garver H, et al. The development of hypertension and hyperaldosteronism in a rodent model of life-long obesity. Endocrinology. 2012;153:1764–73.PubMedCrossRef Northcott CA, Fink GD, Garver H, et al. The development of hypertension and hyperaldosteronism in a rodent model of life-long obesity. Endocrinology. 2012;153:1764–73.PubMedCrossRef
33.
Zurück zum Zitat Deji N, Kume S, Araki S, et al. Role of angiotensin II-mediated AMPK inactivation on obesity-related salt-sensitive hypertension. Biochem Biophys Res Commun. 2012;418:559–64.PubMedCrossRef Deji N, Kume S, Araki S, et al. Role of angiotensin II-mediated AMPK inactivation on obesity-related salt-sensitive hypertension. Biochem Biophys Res Commun. 2012;418:559–64.PubMedCrossRef
34.
Zurück zum Zitat Thatcher S, Yannikouris F, Gupte M, Cassis L. The adipose renin-angiotensin system: role in cardiovascular disease. Mol Cell Endocrinol. 2009;302:111–7.PubMedCrossRef Thatcher S, Yannikouris F, Gupte M, Cassis L. The adipose renin-angiotensin system: role in cardiovascular disease. Mol Cell Endocrinol. 2009;302:111–7.PubMedCrossRef
35.
Zurück zum Zitat Yasue S, Masuzaki H, Okada S, et al. Adipose tissue-specific regulation of angiotensinogen in obese humans and mice: impact of nutritional status and adipocyte hypertrophy. Am J Hypertens. 2010;23:425–31.PubMedCrossRef Yasue S, Masuzaki H, Okada S, et al. Adipose tissue-specific regulation of angiotensinogen in obese humans and mice: impact of nutritional status and adipocyte hypertrophy. Am J Hypertens. 2010;23:425–31.PubMedCrossRef
36.
Zurück zum Zitat O’Seaghdha CM, Hwang SJ, Vasan RS, et al. Correlation of renin angiotensin and aldosterone system activity with subcutaneous and visceral adiposity: the Framingham heart study. BMC Endocr Disord. 2012;12:3.PubMedCrossRef O’Seaghdha CM, Hwang SJ, Vasan RS, et al. Correlation of renin angiotensin and aldosterone system activity with subcutaneous and visceral adiposity: the Framingham heart study. BMC Endocr Disord. 2012;12:3.PubMedCrossRef
Metadaten
Titel
Animal Models in Obesity and Hypertension
verfasst von
Gabriella Segal-Lieberman
Talma Rosenthal
Publikationsdatum
01.06.2013
Verlag
Current Science Inc.
Erschienen in
Current Hypertension Reports / Ausgabe 3/2013
Print ISSN: 1522-6417
Elektronische ISSN: 1534-3111
DOI
https://doi.org/10.1007/s11906-013-0338-3

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