Control of Energy Balance by the Brain Renin-Angiotensin System

Claflin, Kristin E.; Grobe, Justin L

doi:10.1007/s11906-015-0549-x

Cited by 30 publications

(23 citation statements)

References 89 publications

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“…Not only does adipose tissue have a local RAS 12,28 but serum levels of major the components of the RAS (renin, AGT, ACE) are elevated in obesity. 10 TNF-α is commonly considered as one of the initiators of the pro-inflammatory cascade, which can induce the production of other cytokines.…”

Section: Discussionmentioning

confidence: 99%

Central Renin–Angiotensin System Activation and Inflammation Induced by High-Fat Diet Sensitize Angiotensin II–Elicited Hypertension

Xue

Thunhorst

et al. 2016

Hypertension

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Obesity has been shown to promote renin-angiotensin system (RAS) activity and inflammation in the brain and to be accompanied by increased sympathetic activity and blood pressure (BP). Our previous studies demonstrated that administration of a subpressor dose of angiotensin (Ang) II sensitizes subsequent Ang II-elicited hypertension. The present study tested whether high fat diet (HFD) feeding also sensitizes the Ang II-elicited hypertensive response and whether HFD-induced sensitization is mediated by an increase in RAS activity and inflammatory mechanisms in the brain. HFD did not increase baseline BP, but enhanced the hypertensive response to Ang II compared to a normal fat diet. The sensitization produced by the HFD was abolished by concomitant central infusions of either a tumor necrosis factor α (TNF-α) synthesis inhibitor, pentoxifylline, an Ang II type 1 receptor (AT1-R) blocker, irbesartan or an inhibitor of microglial activation, minocycline. Furthermore, central pretreatment with TNF-α mimicked the sensitizing action of a central subpressor dose of Ang II, whereas central pentoxifylline or minocycline abolished this Ang II-induced sensitization. RT-PCR analysis of lamina terminalis tissue indicated that HFD feeding, central TNF-α or a central subpressor dose of Ang II upregulated mRNA expression of several components of the RAS and proinflammatory cytokines, whereas inhibition of AT1-R and of inflammation reversed these changes. The results suggest that HFD-induced sensitization of Ang II-elicited hypertension is mediated by upregulation of the brain RAS and of central proinflammatory cytokines.

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Section: Discussionmentioning

confidence: 99%

Central Renin–Angiotensin System Activation and Inflammation Induced by High-Fat Diet Sensitize Angiotensin II–Elicited Hypertension

Xue

Thunhorst

et al. 2016

Hypertension

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“…Leptin action at proopiomelanocortin (POMC) neurons of the ARC is critical for BP regulation (8), and both POMC and agouti-related peptide (AgRP) neurons mediate the metabolic effects of leptin in the ARC. While the brain RAS has been implicated in the control of selected aspects of energy balance including food intake and energy expenditure, the specific brain regions involved and the neurocircuitry that mediates these effects are unknown (9,10).…”

Section: Introductionmentioning

confidence: 99%

Angiotensin AT1A receptors on leptin receptor–expressing cells control resting metabolism

Claflin¹,

Sandgren²,

Lambertz³

et al. 2017

Journal of Clinical Investigation

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“…Accumulating evidence indicates that obesity causes chronic low-grade inflammation associated with systemic metabolic dysfunction that is accompanied by increased renin-angiotensin system (RAS) activity. 1,2 Recent studies have demonstrated that the RAS and proinflammatory cytokines (PICs) in the central nervous system (CNS) play a critical role in mediating obesity-induced sensitization and obesity-related hypertension. 3,4,5 …”

Section: Introductionmentioning

confidence: 99%

Leptin Mediates High-Fat Diet Sensitization of Angiotensin II–Elicited Hypertension by Upregulating the Brain Renin–Angiotensin System and Inflammation

Xue

Zhang

et al. 2016

Hypertension

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Obesity is characterized by increased circulating levels of the adipocyte-derived hormone leptin, which can increase sympathetic nerve activity and raise blood pressure. A previous study revealed that rats fed a high fat diet (HFD) have an enhanced hypertensive response to subsequent angiotensin (Ang) II administration that is mediated at least in part by increased activity of brain renin-angiotensin system (RAS) and proinflammatory cytokines (PICs). The present study tested whether leptin mediates this HFD-induced sensitization of Ang II-elicited hypertension by interacting with brain RAS and PICs mechanisms. Rats fed a HFD for 3 weeks had significant increases in white adipose tissue mass, plasma leptin levels and mRNA expression of leptin and its receptors in the lamina terminalis (LT) and hypothalamic paraventricular nucleus (PVN). Central infusion of a leptin receptor antagonist during HFD feeding abolished HFD sensitization of Ang II-elicited hypertension. Furthermore, central infusion of leptin mimicked the sensitizing action of HFD. Concomitant central infusions of the AT1-R antagonist irbesartan, the TNF-α synthesis inhibitor pentoxifylline, or the inhibitor of microglial activation minocycline prevented the sensitization produced by central infusion of leptin. RT-PCR analysis indicated that either HFD or leptin administration upregulated mRNA expression of several components of the RAS and PICs in the LT and PVN. The leptin antagonist and the inhibitors of AT1-R, TNF-α synthesis and microglial activation all reversed the expression of these genes. The results suggest that HFD-induced sensitization of Ang II-elicited hypertension is mediated by leptin through upregulation of central RAS and PICs.

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Control of Energy Balance by the Brain Renin-Angiotensin System

Cited by 30 publications

References 89 publications

Central Renin–Angiotensin System Activation and Inflammation Induced by High-Fat Diet Sensitize Angiotensin II–Elicited Hypertension

Central Renin–Angiotensin System Activation and Inflammation Induced by High-Fat Diet Sensitize Angiotensin II–Elicited Hypertension

Angiotensin AT1A receptors on leptin receptor–expressing cells control resting metabolism

Leptin Mediates High-Fat Diet Sensitization of Angiotensin II–Elicited Hypertension by Upregulating the Brain Renin–Angiotensin System and Inflammation

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