Leptin and neuropeptide Y (NPY) modulate nitric oxide synthase: further evidence for a role of nitric oxide in feeding

Morley, John E.; Alshaher, Motaz; Farr, Susan A.; Flood, James F.; Kumar, Vijaya B.

doi:10.1016/s0196-9781(99)00012-1

Cited by 95 publications

(53 citation statements)

References 45 publications

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“…This is firm evidence of NO activity in BAT, as there is no other source of NO x in the incubation medium. This also confirms previous findings suggesting that BAT produces NO [6,[10][11][12][13]. Furthermore, this study showed that cold acclimation and repetitive immobilization stress, which are known to enhance the thermogenic capacity of BAT [1,3], enhanced the production of NO x in the basal condition.…”

Section: Discussionsupporting

confidence: 92%

Nitric Oxide and Thermogenic Function of Brown Adipose Tissue in Rats.

Saha

Kuroshima²

2000

JJP

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Brown adipose tissue (BAT) is a thermogenic organ and its thermogenesis is indispensable when nonshivering thermogenesis is the main source of heat for body temperature regulation in mammals. Exposure of animals to a cold ambient temperature activates BAT, enhancing nonshivering thermogenesis to maintain a constant body temperature. Daily immobilization stress for several hours over several weeks in rats also activates the BAT function, and when these animals are exposed to a cold ambient temperature, they show an enhanced nonshivering thermogenic capacity, a phenomenon which is termed as cross adaptation [1][2][3][4]. Both cold exposure and repetitive immobilization stress may stimulate the sympathetic nervous system, initiating BAT activities responsible for the enhancement of nonshivering thermogenesis.Blood flow perfusing BAT determines the thermogenic activity of the tissue. When the rats are exposed to cold or injected with the sympathetic nerve transmitter noradrenaline, the tissue is perfused with more blood to meet the increased metabolic demand. This increase in BAT blood flow ceases if the rats are coinjected with N -nitro-L-arginine methyl ester (L-NAME; a nitric oxide synthase inhibitor), implying a role for nitric oxide (NO) in the regulation of BAT blood flow [5]. This finding justified further investigation to explore the role of NO in BAT nonshivering thermogenesis. Subsequently, we reported that chronic treatment with L-NAME decreases the nonshivering thermogenic capacity of rats. The L-NAME-treated rats develop hypothermia on acute exposure to a cold ambient temperature and do not show any response to noradrenaline that normally increases oxygen consumption in vivo [6]. The thermogenic capacity of BAT isolated from these rats, as estimated by DNA content and in vitro oxygen consumption, is also found to be suppressed. In these previous studies, we adopted pharmacological means to suppress the NO synthase, but did not show any firm evidence of NO synthesis in BAT. In addition, it is not known if the physiological conditions that are known to enhance adaptive thermogenesis would enhance the capacity for NO synthesis in BAT. In this study, therefore, we addressed the question of firm evidence of NO in BAT Japanese Journal of Physiology, 50, 337-342, 2000 Key words: brown adipose tissue, nitric oxide, in vitro oxygen consumption, nonshivering thermogenesis. Abstract:To clarify the effects of cold acclimation and immobilization stress adaptation of rats on nitric oxide (NO) activity in interscapular brown adipose tissue (BAT), we incubated neatly diced (1-mm 3 blocks) BAT in a metabolic chamber for respiration, measured oxygen consumption using a Clark electrode, and estimated NO release in the buffer medium by measuring nitrite plus nitrate (NO x ) using the Griess method (diazotization reaction). The production of NO x in the buffer medium confirmed that BAT releases NO, as there is no other source of NO x in the system. The NO activity was observed in the basal condition and increased with no...

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Section: Discussionsupporting

confidence: 92%

Nitric Oxide and Thermogenic Function of Brown Adipose Tissue in Rats.

Saha

Kuroshima²

2000

JJP

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“…16 Emerging evidence has also suggested that the sympathoinhibitor neurotransmitter nitric oxide (NO) [17][18][19] and the sympathoexcitatory neurotransmitter glutamate, through N-methyl-d-aspartate receptor (NMDAr), [20][21][22][23] play a role on energy metabolism. Recent data have shown that central lipid infusion by the carotid artery deregulates hepatic insulin signaling in rats, in part, by increasing neuronal NO synthase (nNOS) activity in hypothalamus, suggesting that nNOS in the hypothalamus might be involved with the development of insulin resistance.…”

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confidence: 99%

Increasing Angiotensin-(1–7) Levels in the Brain Attenuates Metabolic Syndrome–Related Risks in Fructose-Fed Rats

et al. 2014

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Metabolic syndrome (MetS) is currently recognized as a worldwide health problem, 1,2 and the substantial increase in fructose intake in human diet, especially as high-fructose corn syrup, has been considered a potential factor predisposing humans to MetS. 3,4 MetS is a cluster of different risk factors, such as increase in visceral fat deposition, glucose intolerance, dyslipidemia, and hypertension, which increases the risk of development of cardiovascular and renal diseases and type II diabetes mellitus. 2,5 Recent studies in rodents have shown that the renin-angiotensin system, through the inappropriate overactivity of angiotensin (Ang) II on Ang II type 1 (AT 1 ) receptor especially in the circulation and in the white adipose tissue, plays a pivotal role on the pathogenesis of MetS. [6][7][8] Peripheral blockade of Ang II synthesis or its action on AT 1 receptor attenuates metabolic disorders in obese rodents. [6][7][8] In contrast, the other functional arm of renin-angiotensin system, represented by the actions of Ang-(1-7) on Mas receptor, has been recognized widely as a counter-regulatory axis of Ang II/AT 1 receptor actions.Recent studies have shown that chronic increases in peripheral Ang-(1-7)/Mas receptor activity play a protective role in the regulation of cardiovascular and energy metabolism. Transgenic rats with increased Ang-(1-7) levels in the circulation [TGR(A1-7)3292] are protected against cardiac dysfunction, fibrosis, and hypertension when subjected to deoxycorticosterone (DOCA) acetate-salt model 9 and have enhanced resting glucose and lipid metabolism. 10 Accordingly, Giani et al 11,12 showed that chronic subcutaneous infusion of Ang-(1-7) improved insulin resistance, hypertension, and cardiac remodeling in fructose-fed rats. However, genetic deletion of Mas receptor alters glucose and lipid metabolism and the neural control of blood pressure, inducing a state of MetS. [13][14][15] Taken together, these data provide a clear evidence of a protective role of peripheral Ang-(1-7)/Mas receptor axis in the regulation of cardiovascular system and energy metabolism.Our group showed recently that chronic increase in Ang-(1-7) levels in the brain attenuates DOCA-salt hypertension, and that this effect is related to a dramatic beneficial role Abstract-We evaluated effects of chronic intracerebroventricular infusion of angiotensin (Ang)-(1-7) on cardiovascular and metabolic parameters in fructose-fed (FF) rats. After 6 weeks of fructose intake (10% in drinking water), SpragueDawley rats were subjected to intracerebroventricular infusion of Ang-(1-7) (200 ng/h; FF+A7 group) or 0.9% sterile saline (FF group) for 4 weeks with continued access to fructose. Compared with control rats, FF rats had increased mean arterial pressure and cardiac sympathetic tone with impaired baroreflex sensitivity. FF rats also presented increased circulating triglycerides, leptin, insulin, and glucose with impaired glucose tolerance. Furthermore, relative weights of liver and retroperitoneal adipose tissue were increased...

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“…Insulin injected in the nucleus tractus solitarius (NTS) stimulates nNOS (41), whereas inhibition of nNOS in the NTS prevents insulin's ability to lower blood pressure (41). In contrast, leptin decreases nitric oxide synthase (NOS) activity in the brain (11,30). Both activity and mRNA of NOS are elevated in the hypothalamus of leptin-deficient obese (ob/ob) mice (31).…”

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confidence: 99%

Glucose, insulin, and leptin signaling pathways modulate nitric oxide synthesis in glucose-inhibited neurons in the ventromedial hypothalamus

Canabal¹,

Song²,

Potian³

et al. 2007

American Journal of Physiology-Regulatory, Integrative and Comp

123

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Canabal DD, Song Z, Potian JG, Beuve A, McArdle JJ, Routh VH. Glucose, insulin and leptin signaling pathways modulate nitric oxide synthesis in glucose-inhibited neurons in the ventromedial hypothalamus. Am J Physiol Regul Integr Comp Physiol 292: R1418 -R1428, 2007. First published December 24, 2006; doi:10.1152/ajpregu.00216.2006.-Glucose-sensing neurons in the ventromedial hypothalamus (VMH) are involved in the regulation of glucose homeostasis. Glucosesensing neurons alter their action potential frequency in response to physiological changes in extracellular glucose, insulin, and leptin. Glucose-excited neurons decrease, whereas glucose-inhibited (GI) neurons increase, their action potential frequency when extracellular glucose is reduced. Central nitric oxide (NO) synthesis is regulated by changes in local fuel availability, as well as insulin and leptin. NO is involved in the regulation of food intake and is altered in obesity and diabetes. Thus this study tests the hypothesis that NO synthesis is a site of convergence for glucose, leptin, and insulin signaling in VMH glucose-sensing neurons. With the use of the NO-sensitive dye 4-amino-5-methylamino-2Ј,7Ј-difluorofluorescein in conjunction with the membrane potential-sensitive dye fluorometric imaging plate reader, we found that glucose and leptin suppress, whereas insulin stimulates neuronal nitric oxide synthase (nNOS)-dependent NO production in cultured VMH GI neurons. The effects of glucose and leptin were mediated by suppression of AMP-activated protein kinase (AMPK). The AMPK activator 5-aminoimidazole-4-carboxamide-1-␤-4-ribofuranoside (AICAR) increased both NO production and neuronal activity in GI neurons. In contrast, the effects of insulin on NO production were blocked by the phosphoinositide 3-kinase inhibitors wortmannin and LY-294002. Furthermore, decreased glucose, insulin, and AICAR increase the phosphorylation of VMH nNOS, whereas leptin decreases it. Finally, VMH neurons express soluble guanylyl cyclase, a downstream mediator of NO signaling. Thus NO may mediate, in part, glucose, leptin, and insulin signaling in VMH glucose-sensing neurons. ventromedial hypothalamus; glucose-sensing neurons; leptin; insulin; nitric oxide; adenosine 5Ј-monophosphate-activated protein kinase THE VENTROMEDIAL HYPOTHALAMUS (VMH), which contains the ventromedial (VMN) and arcuate (ARC) nuclei, is critical for the regulation of glucose and energy homeostasis (34). This region contains specialized neurons whose activity is regulated by physiologically relevant changes in extracellular glucose (36,37,42). Glucose-excited (GE) neurons decrease, whereas glucose-inhibited (GI) neurons increase, their action potential frequency (APF) when extracellular glucose is reduced (36). GE neurons activate ATP-sensitive K ϩ (K ATP ) channels in response to decreased glucose. GI neurons appear to close an ATP-activated Cl Ϫ channel, although the identity of this channel is unknown (36). Glucose-sensing neurons also possess insulin and leptin receptors (22,39,40,42). Thus gluc...

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Leptin and neuropeptide Y (NPY) modulate nitric oxide synthase: further evidence for a role of nitric oxide in feeding

Cited by 95 publications

References 45 publications

Nitric Oxide and Thermogenic Function of Brown Adipose Tissue in Rats.

Nitric Oxide and Thermogenic Function of Brown Adipose Tissue in Rats.

Increasing Angiotensin-(1–7) Levels in the Brain Attenuates Metabolic Syndrome–Related Risks in Fructose-Fed Rats

Glucose, insulin, and leptin signaling pathways modulate nitric oxide synthesis in glucose-inhibited neurons in the ventromedial hypothalamus

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