Sympathetic nervous system behavior in human obesity

Davy, Kevin P.; Orr, Jeb S.

doi:10.1016/j.neubiorev.2008.05.024

Cited by 145 publications

(136 citation statements)

References 76 publications

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“…The literature indicates large discrepancies among studies that report low, unchanged and high activity of the sympathetic nervous system during obesity in both subjects and experimental animal models (Tentolouris et al 2006). It has been claimed that the paradoxical sympathetic activity in obese individuals is tissue/organ specific (Davy & Orr 2009), but this phenomenon is not completely understood. Alternatively, it is known that parasympathetic overactivity has a strong association with hyperinsulinemia, insulin resistance, and the development of obesity (Rohner-Jeanrenaud et al 1983, Tentolouris et al 2006, which are in agreement with our data.…”

Section: Discussionmentioning

confidence: 99%

Poor pubertal protein nutrition disturbs glucose-induced insulin secretion process in pancreatic islets and programs rats in adulthood to increase fat accumulation

Oliveira¹,

Lisboa²,

Moura³

et al. 2012

Journal of Endocrinology

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Similar to gestation/lactation, puberty is also a critical phase in which neuronal connections are still being produced and during which metabolic changes may occur if nutrition is disturbed. In the present study we aimed to determine whether peripubertal protein restriction induces metabolic programming. Thirty-day-old male rats were fed either a low protein (LP group) diet (4% w/w protein) or a normal protein (NP group) diet (23%) until 60 days of age, when they received the NP diet until they were 120 days old. Body weight (BW), food intake, fat tissue accumulation, glucose tolerance, and insulin secretion were evaluated. The nerve electrical activity was recorded to evaluate autonomous nervous system (ANS) function. Adolescent LP rats presented hypophagia and lower BW gain during the LP diet treatment (P!0.001). However, the food intake and BW gain by the LP rats were increased (P!0.001) after the NP diet was resumed. The LP rats presented mild hyperglycemia, hyperinsulinemia, severe hyperleptinemia upon fasting, peripheral insulin resistance and increased fat tissue accumulation and vagus nerve activity (P!0.05). Glucoseinduced insulin secretion was greater in the LP islets than in the NP islets; however, the cholinergic response was decreased (P!0.05). Compared with the islets from the NP rats, the LP islets showed changes in the activity of muscarinic receptors (P!0.05); in addition, the inhibition of glucose-induced insulin secretion by epinephrine was attenuated (P!0.001). Protein restriction during adolescence caused high-fat tissue accumulation in adult rats. Islet dysfunction could be related to an ANS imbalance.

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Section: Discussionmentioning

confidence: 99%

Poor pubertal protein nutrition disturbs glucose-induced insulin secretion process in pancreatic islets and programs rats in adulthood to increase fat accumulation

Oliveira¹,

Lisboa²,

Moura³

et al. 2012

Journal of Endocrinology

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“…Obesity increases the risk of hypertension, secondary to activation of the sympathetic nervous system (1,2). However, the cellular molecular mechanisms in brain that link increases in adiposity with elevations in sympathetic nerve activity (SNA) remain unclear.…”

Section: Introductionmentioning

confidence: 99%

Arcuate neuropeptide Y inhibits sympathetic nerve activity via multiple neuropathways

Shi¹,

Madden²,

Brooks³

2017

Journal of Clinical Investigation

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Obesity increases sympathetic nerve activity (SNA) via activation of proopiomelanocortin neurons in the arcuate nucleus (ArcN), and this action requires simultaneous withdrawal of tonic neuropeptide Y (NPY) sympathoinhibition. However, the sites and neurocircuitry by which NPY decreases SNA are unclear. Here, using designer receptors exclusively activated by designer drugs (DREADDs) to selectively activate or inhibit ArcN NPY neurons expressing agouti-related peptide (AgRP) in mice, we have demonstrated that this neuronal population tonically suppresses splanchnic SNA (SSNA), arterial pressure, and heart rate via projections to the paraventricular nucleus (PVN) and dorsomedial hypothalamus (DMH The Journal of Clinical Investigation R E S E A R C H A R T I C L E2 8 6 9 jci.org Volume 127 Number 7 July 2017We next tested whether selective excitation or inhibition of ArcN NPY/AgRP neurons alters splanchnic SNA (SSNA), mean AP (MAP), or heart rate (HR) ( Figure 1). As shown in representative experiments ( Figure 1, A and B) and grouped data ( Figure 1C), in ArcN hM3Dq mice, i.p. CNO (0.3 mg/kg) promptly decreased SSNA, MAP, and HR, whereas i.p. saline had no effects. The suppression induced by CNO was sustained for at least 1 hour, and, in mice with longer recordings, up to 4 hours (data not shown). In rats, guinea pigs, and humans, CNO can have nonspecific effects due to its conversion to clozapine (17, 18). However, in WT mice receiving the Cre-dependent hM3Dq vector, neither i.p. saline nor CNO significantly altered these variables, suggesting that CNO was not exerting its effects independently of DREADD activation. A separate group of Agrp-IRES-Cre mice instead received AAV-hM4Di-mCherry in the ArcN (Figure 1, D-F). In these ArcN hM4Di mice, i.p. CNO (0.3 and 1 mg/kg) dose-dependently increased SSNA, MAP, and HR, although the responses developed both NPY-GFP and Cre in AgRP neurons. In agreement with an earlier study using a different approach (14), we found that while not all NPY-GFP neurons had visible hM3Dq-mCherry labeling, 100% of the hM3Dq-mCherry-marked neurons also expressed NPY-GFP (Supplemental Figure 1; supplemental material available online with this article; https://doi.org/10.1172/JCI92008DS1). WT mice never expressed the Cre-dependent DREADD. In a second set of experiments, 2 or more weeks after Agrp-IRES-Cre mice received hM3Dq bilaterally in the ArcN, CNO (0.3 mg/kg) or the saline vehicle was administered i.p., and food intake was monitored for the following 4 hours. As shown previously (14), i.p. CNO, but not saline, rapidly evoked food intake in ArcN hM3Dq mice (Supplemental Figure 1). Conversely, activation of inhibitory DREADDs in ArcN hM4Di mice at the beginning of the feeding period (lights out) inhibited food intake (Supplemental Figure 1). Therefore, we anatomically and functionally confirm that this approach selectively targets ArcN NPY/AgRP neurons. The Journal of Clinical Investigation R E S E A R C H A R T I C L E2 8 7 0jci.org Volume 127 Number 7 July 2017neurons were also observ...

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“…Visceral adiposity may have a major role in the occurrence of hypertension, diabetes mellitus, hyperlipidemia, and atherosclerosis not only in obese humans but also in animal models of diet-induced obesity (Davy & Orr 2009, Hall et al 2010. Recent evidence revealed several biological and genetic differences between intraabdominal visceral fat and peripheral subcutaneous fat.…”

Section: Introductionmentioning

confidence: 99%

Obesity-related hypertension: possible pathophysiological mechanisms

Vaněčková¹,

Maletı́nská²,

Behuliak³

et al. 2014

Journal of Endocrinology

129

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Hypertension is one of the major risk factors of cardiovascular diseases, but despite a century of clinical and basic research, the discrete etiology of this disease is still not fully understood. The same is true for obesity, which is recognized as a major global epidemic health problem nowadays. Obesity is associated with an increasing prevalence of the metabolic syndrome, a cluster of risk factors including hypertension, abdominal obesity, dyslipidemia, and hyperglycemia. Epidemiological studies have shown that excess weight gain predicts future development of hypertension, and the relationship between BMI and blood pressure (BP) appears to be almost linear in different populations. There is no doubt that obesity-related hypertension is a multifactorial and polygenic trait, and multiple potential pathogenetic mechanisms probably contribute to the development of higher BP in obese humans. These include hyperinsulinemia, activation of the renin-angiotensin-aldosterone system, sympathetic nervous system stimulation, abnormal levels of certain adipokines such as leptin, or cytokines acting at the vascular endothelial level. Moreover, some genetic and epigenetic mechanisms are also in play. Although the full manifestation of both hypertension and obesity occurs predominantly in adulthood, their roots can be traced back to early ontogeny. The detailed knowledge of alterations occurring in the organism of experimental animals during particular critical periods (developmental windows) could help to solve this phenomenon in humans and might facilitate the age-specific prevention of human obesity-related hypertension. In addition, better understanding of particular pathophysiological mechanisms might be useful in so-called personalized medicine. Key Words" obesity " hypertension " sympathetic nervous system " renin-angiotensin system " critical developmental periods " epigenetics " rat

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Sympathetic nervous system behavior in human obesity

Cited by 145 publications

References 76 publications

Poor pubertal protein nutrition disturbs glucose-induced insulin secretion process in pancreatic islets and programs rats in adulthood to increase fat accumulation

Poor pubertal protein nutrition disturbs glucose-induced insulin secretion process in pancreatic islets and programs rats in adulthood to increase fat accumulation

Arcuate neuropeptide Y inhibits sympathetic nerve activity via multiple neuropathways

Obesity-related hypertension: possible pathophysiological mechanisms

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