Neuropeptide Y Expression and Endogenous Leptin Concentrations in a Dietary Model of Obesity

Lauterio, Thomas J.; Davies, Michael J.; DeAngelo, Mark; Peyser, M. Reuben; Lee, James

doi:10.1002/j.1550-8528.1999.tb00439.x

Cited by 32 publications

(27 citation statements)

References 38 publications

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“…In accordance with previous data, 29 in OP rats after 12 weeks on the diet, plasma insulin was increased Ϸ2-fold compared with that in OR rats (Table). As expected, pioglitazone prevented the elevation in plasma insulin in OP rats (Table).…”

Section: Body Weight Circulating Insulin and Sodium Excretion In Opsupporting

confidence: 92%

Pioglitazone Prevents Hypertension and Reduces Oxidative Stress in Diet-Induced Obesity

et al. 2004

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Abstract-The objective of this study was to determine the effect of pioglitazone on blood pressure (BP) and oxidative balance in obese, hypertensive, Sprague-Dawley rats and to identify some of the molecular mechanisms involved. After 12 weeks of a moderately high-fat diet, rats diverged into obesity-prone (OP) and obesity-resistant (OR) groups (nϭ6 per group). At the end of the diet, peroxisome proliferator activated receptor-␥ (PPAR␥) mRNA expression and activity in the renal cortex and medulla of OP rats were significantly lower compared with that in OR rats. Pioglitazone treatment increased PPAR␥ expression and activity in OP rats, suggesting a possible direct ligand-related effect of pioglitazone. As opposed to the untreated OP group, which showed moderate hypertension (systolic BPϭ159Ϯ5.3 mm Hg) after 12 weeks, pioglitazone-treated rats were normotensive (systolic BPϭ123.9Ϯ2.7 mm Hg). Insulin production was reduced by 2-fold in the OP group treated with pioglitazone. Urinary isoprostanes and renal lipid peroxides were also reduced in OP rats treated with pioglitazone compared with untreated counterparts. Also, expression of p47phox and gp91phox, both increased in OP versus OR rats, was reduced in the former by pioglitazone treatment. In addition, pioglitazone treatment increased nitrate/nitrite excretion and expression of renal endothelial and neuronal nitric oxide synthase. Collectively, the results show that pioglitazone treatment prevented hypertension and renal oxidative stress both by reducing free-radical production and by increasing nitric oxide production/availability. Key Words: kidney Ⅲ oxidative stress Ⅲ free radicals Ⅲ nitric oxide Ⅲ vitamins O besity is a widespread and increasingly prevalent condition associated with a large number of comorbid diseases, one of the most important of which is obesityinduced hypertension. A pleiotropic class of molecules involved in regulation of gene expression in a variety of metabolic and cardiovascular conditions is the peroxisome proliferator-activated receptors (PPARs). PPARs are ligandactivated transcription factors that form heterodimers with the 9-cis retinoic acid receptor RXR␣. 1 PPAR␥ is one of the three PPAR isoforms and is one of the major regulators of adipogenesis. 2 In addition, PPAR␥ exerts pleiotropic effects on blood pressure, lipid metabolism, and insulin action.Recent genetic analysis showed that 2 dominant-negative mutations in PPAR␥ were associated with severe hypertension in humans. 3,4 Consistent with these findings, thiazolidinendiones, the insulin-sensitizer drugs (pioglitazone, rosiglitazone) that are also high-affinity PPAR␥ ligands, 5 have been shown to lower blood pressure (BP) in a variety of hypertensive animal models 6 -8 as well as in diabetic and nondiabetic, 9 hypertensive humans. However, the mechanism underlying the antihypertensive effects of PPAR␥ agonists is not known. PPAR␥ and RXR have been found constitutively expressed in the inner medullary collecting ducts, thick ascending limb, glomerulus, and renal medullary mic...

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Section: Body Weight Circulating Insulin and Sodium Excretion In Opsupporting

confidence: 92%

Pioglitazone Prevents Hypertension and Reduces Oxidative Stress in Diet-Induced Obesity

et al. 2004

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“…Another possible explanation for the earlier increase in BP in OP rats on a high-salt diet may be related to the pressor effect of leptin, as recently reported (23). Our own data or data reported by others (29) indicate that OP rats are hyperleptinemic by the end of the diet. Data showed that high-salt diets induced a significant 40% increase in plasma leptin in OP rats.…”

Section: Discussionsupporting

confidence: 72%

Effect of salt on hypertension and oxidative stress in a rat model of diet-induced obesity

Dobrian

Schriver

Lynch

et al. 2003

American Journal of Physiology-Renal Physiology

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. Effect of salt on hypertension and oxidative stress in a rat model of diet-induced obesity. Am J Physiol Renal Physiol 285: F619-F628, 2003. First published June 10, 2003 10.1152 10. /ajprenal.00388. 2002 diet is known to induce or aggravate hypertension in animal models of hypertension and in humans. When Sprague-Dawley rats (n ϭ 60) are fed a moderately high-fat diet (32% kcal fat, 0.8% NaCl) for 10 wk, about one-half develop obesity [obesity prone (OP)] and mild hypertension, whereas the other half [obesity resistant (OR)] maintain body weight equivalent to a low-fat control (C) and are normotensive. The aim of this study was to test the effect of high-NaCl diets (2 and 4% NaCl) on the development of hypertension and obesity, oxidative stress, and renal function. Both 2 and 4% NaCl induced an early increase in systolic blood pressure of OP but not OR or C rats. High-salt intake induced an increase in the size and reduction in number of adipocytes, concomitant to a twofold increase in circulating leptin in OP rats. Aortic superoxide generation indicated a 2.8-fold increase in the OP high-salt vs. normalsalt groups, whereas urine isoprostanes were not significantly increased. Also, hydroxynonenal protein adducts in the kidney were highly increased in OP rats on 2 and 4% NaCl, indicating oxidative stress in the renal tissue. Urine albumin was increased threefold in the OP on 2% NaCl and fourfold in the same group on 4% NaCl vs. 0.8% NaCl. Kidney histology indicated a higher degree of glomerulosclerosis in OP rats on high-salt diets. In summary, high-salt diet accelerated the development but did not increase the severity of hypertension; high salt increased oxidative stress in the vasculature and kidney and induced kidney glomerulosclerosis and microalbuminuria. Also, the OP rats on high salt displayed adipocyte hypertrophy and increased leptin production.glomerulosclerosis; kidney; leptin; sodium dietary OBESITY IS A complex, multifactorial disease that is associated with essential hypertension in ϳ78% of men and ϳ65% of women, as indicated by the data from the Framingham Heart Study (25). Another important contributor to hypertension in humans is the excessive consumption of dietary salt, and epidemiological studies have demonstrated a significant but weak relation between salt intake and hypertension (32, 33). Some, but not all, interventional studies have shown that salt restriction may lower blood pressure (BP) (19,33). Some recent studies report correlation among hypertension, salt sensitivity, and insulin resistance in obese humans (38), whereas others fail to observe a significant relationship (8). Animal models of obesity, hypertension, and insulin resistance display differences with respect to salt sensitivity. In Zucker rats, there is a clear correlation between salt intake and the severity of hypertension (4, 47), whereas in chronic hyperinsulinemic Sprague-Dawley (SD) rats, hypertension is not salt sensitive, albeit a shift in pressure-natriuresis relationship was reported (2). One important cont...

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“…Leptin can generate oxidative stress, as has been reported for endothelial cells in culture. 45 In addition, leptin indirectly stimulates production of inflammatory cytokines such as interleukin-6 and tumor necrosis factor-␣, which increase NADPH oxidase production. 9 However, no data suggest that leptin stimulates ROS generation in the brain.…”

Section: Discussionmentioning

confidence: 99%

Sympathoexcitation by Oxidative Stress in the Brain Mediates Arterial Pressure Elevation in Obesity-Induced Hypertension

et al. 2009

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Background-Obesity is one of the major risk factors for cardiovascular disease and is often associated with increased oxidative stress and sympathoexcitation. We have already suggested that increased oxidative stress in the brain modulates the sympathetic regulation of arterial pressure in salt-sensitive hypertension, which is often associated with obesity. The present study was performed to determine whether oxidative stress could mediate central sympathoexcitation in the initial stage of obesity-induced hypertension. Methods and Results-Four-week-old male Sprague-Dawley rats were fed a high-fat (45% kcal as fat) or low-fat (10% kcal as fat) diet for 6 weeks. Fat loading elicited hypertension and sympathoexcitation, along with visceral obesity. In urethane-anesthetized and artificially ventilated rats, arterial pressure and renal sympathetic nerve activity decreased in a dose-dependent fashion when 53 or 105 mol/kg tempol, a membrane-permeable superoxide dismutase mimetic, was infused into the lateral cerebral ventricle. Central tempol reduced arterial pressure and renal sympathetic nerve activity to a significantly greater extent in high-fat diet-fed hypertensive rats than in low-fat diet-fed normotensive rats. Intracerebroventricular apocynin or diphenyleneiodonium, a reduced NADPH oxidase inhibitor, also elicited markedly greater reductions in arterial pressure and renal sympathetic nerve activity in the high-fat diet-fed rats. In addition, fat loading increased NADPH oxidase activity and NADPH oxidase subunit p22 phox , p47 phox , and gp91 phox mRNA expression in the hypothalamus. Key Words: brain Ⅲ hypertension Ⅲ obesity Ⅲ oxidative stress Ⅲ sympathetic nervous system M etabolic syndrome, a complex of highly debilitating disorders that consist of hypertension, diabetes mellitus, and dyslipidemia, is associated with the development of visceral obesity. 1 All of these features are risk factors for atherosclerosis; therefore, the metabolic syndrome results in a high incidence of cardiovascular events. Although hypertension is one of the major components of the metabolic syndrome, the mechanisms through which obesity contributes to hypertension have not been fully elucidated. Conclusions-In Clinical Perspective p 986Sympathetic activation is often associated with obesity. For example, studies using microneurography have consistently shown increased muscle sympathetic nerve activity in obese subjects. 2 Furthermore, muscle sympathetic nerve activity is closely associated with the level of abdominal visceral fat. 3 As expected, a number of studies indicated that sympathetic activation may be involved in obesity-induced hypertension. 4 In young, nondiabetic Japanese men, body mass index correlated with not only mean blood pressure but also pulse rate and plasma norepinephrine. 5 In an animal study, obese Zucker rats, which display hyperphagia-induced obesity caused by a mutation of the leptin receptor, have elevated sympathetic nerve activity and arterial pressure (AP). 6 Autonomic ganglionic blockade decreased m...

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Neuropeptide Y Expression and Endogenous Leptin Concentrations in a Dietary Model of Obesity

Cited by 32 publications

References 38 publications

Pioglitazone Prevents Hypertension and Reduces Oxidative Stress in Diet-Induced Obesity

Pioglitazone Prevents Hypertension and Reduces Oxidative Stress in Diet-Induced Obesity

Effect of salt on hypertension and oxidative stress in a rat model of diet-induced obesity

Sympathoexcitation by Oxidative Stress in the Brain Mediates Arterial Pressure Elevation in Obesity-Induced Hypertension

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