The renin–angiotensin system in the arcuate nucleus controls resting metabolic rate

Deng, Guorui; Grobe, Justin L

doi:10.1097/mnh.0000000000000477

Cited by 15 publications

(17 citation statements)

References 62 publications

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“…This notion is supported by recent studies showing that although animals with diet-induced obesity (DIO) can restore body weight, insulin levels and leptin sensitivity to normal after being switched to a normal fat diet, BP, renal sympathetic nerve activity (RSNA) and the activity of central RAS and PICs remain high ( Prior et al, 2010 ; Maric et al, 2014 ). Genetic disruption of AT1-R in leptin-expressing or agouti-related peptide (AGRP)-expressing cells in the ARC abolishes the thermogenic increase in sympathetic nerve activity in response to leptin, HFD, and deoxycorticosterone acetate (DOCA)-salt ( Claflin et al, 2017 ; Deng and Grobe, 2019 ). In rabbits, three weeks of HFD feeding led to increased BP, heart rate (HR) and RSNA.…”

Section: Introductionmentioning

confidence: 99%

Interactions of the Brain Renin-Angiotensin-System (RAS) and Inflammation in the Sensitization of Hypertension

2020

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Mounting evidence indicates that the renin-angiotensin (RAS) and immune systems interact with one another in the central nervous system (CNS) and that they are importantly involved in the pathogenesis of hypertension. Components comprising the classic RAS were first identified in the periphery, and subsequently, similar factors were found to be generated de novo in many different organs including the brain. There is humoral-neural coupling between the systemic and brain RASs, which is important for controlling sympathetic tone and the release of endocrine factors that collectively determine blood pressure (BP). Similar to the interactions between the systemic and brain RASs is the communication between the peripheral and brain immune systems. Systemic inflammation activates the brain’s immune response. Importantly, the RAS and inflammatory factors act synergistically in brain regions involved in the regulation of BP. This review presents evidence of how such interactions between the brain RAS and central immune mechanisms contribute to the pathogenesis of hypertension. Emphasis focuses on the role of these interactions to induce neuroplastic changes in a central neural network resulting in hypertensive response sensitization (HTRS). Neuroplasticity and HTRS can be induced by challenges (stressors) presented earlier in life such as a low-dose of angiotensin II or high fat diet (HFD) feeding in adults. Similarly, the offspring of mothers with gestational hypertension or of mothers ingesting a HFD during pregnancy are reprogrammed and manifest HTRS when exposed to new stressors as adults. Consideration of the actions and interactions of the brain RAS and inflammatory mediators in the context of the induction and expression of HTRS will provide insights into the etiology of high BP that may lead to new strategies for the prevention and treatment of hypertension.

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Section: Introductionmentioning

confidence: 99%

Interactions of the Brain Renin-Angiotensin-System (RAS) and Inflammation in the Sensitization of Hypertension

2020

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“…Cells of the arcuate nucleus of the hypothalamus (ARC) colocalize the AngII receptor AT1a with the leptin receptor. This AT1 receptor is required for stimulation of thermogenic sympathetic nervous activity, regardless of changes in food intake or blood pressure [ 12 ]. This local hypothalamic system presents a divergent profile compared with the peripherical RAS system [ 10 ].…”

Section: Discussionmentioning

confidence: 99%

“…Cells of the arcuate nucleus (ARC) of the hypothalamus co-express the AngII receptor (AT1a) and the leptin receptor (Lepr). These cells are also required for the specific stimulation of thermogenic sympathetic nervous activity and the subset of changes in the resting metabolic rate but not for the inhibition of food intake, giving the hypothalamic RAS a relevant role in the control of the body’s energy balance [ 12 ]. Multiple physiological and environmental conditions, including diet, determine the proper functioning of this system.…”

Section: Introductionmentioning

confidence: 99%

Hypothalamic Renin–Angiotensin System and Lipid Metabolism: Effects of Virgin Olive Oil versus Butter in the Diet

et al. 2021

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The brain renin–angiotensin system (RAS) has been recently involved in the homeostatic regulation of energy. Our goal was to analyse the influence of a diet rich in saturated fatty acids (butter) against one enriched in monounsaturated fatty acids (olive oil) on hypothalamic RAS, and their relationship with the metabolism of fatty acids. Increases in body weight and visceral fat, together with an increase in aminopeptidase A expression and reductions in AngII and AngIV were observed in the hypothalamus of animals fed with the butter diet. In this group, a marked reduction in the expression of genes related to lipid metabolism (LPL, CD36, and CPT-1) was observed in liver and muscle. No changes were found in terms of body weight, total visceral fat and the expression of hepatic genes related to fatty acid metabolism in the olive oil diet. The expressions of LPL and CD36 were reduced in the muscles, although the decrease was lower than in the butter diet. At the same time, the fasting levels of leptin were reduced, no changes were observed in the hypothalamic expression of aminopeptidase A and decreases were noted in the levels of AngII, AngIV and AngIII. These results support that the type of dietary fat is able to modify the hypothalamic profile of RAS and the body energy balance, related to changes in lipid metabolism.

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“…These data showed that the AT 1a R isoform is expressed in the mouse hypothalamus and selectively in a subset of AgRP neurons expressing SSt3, with no expression of the AT 1b R isoform (Table 1) [68]. It has been hypothesized these SSt3 ARC AgRP neurons project to a unique but unknown set of secondorder neurons to modulate energy expenditure, whereas GABAergic ARC AgRP neurons project to the PVN to participate in the control of food intake and blood pressure [72]. * Data obtained from a recent in silico reanalysis of published RNA-seq cell-specific gene-expression data in hypothalami obtained from male and female C57BL/6N mice during postnatal days 14-28, prior to sexual maturation [68].…”

Section: Angiotensin II Pathwaysmentioning

confidence: 97%

The Arcuate Nucleus of the Hypothalamus and Metabolic Regulation: An Emerging Role for Renin–Angiotensin Pathways

Mehay

Silberman

Arnold

2021

IJMS

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Obesity is a chronic state of energy imbalance that represents a major public health problem and greatly increases the risk for developing hypertension, hyperglycemia, and a multitude of related pathologies that encompass the metabolic syndrome. The underlying mechanisms and optimal treatment strategies for obesity, however, are still not fully understood. The control of energy balance involves the actions of circulating hormones on a widely distributed network of brain regions involved in the regulation of food intake and energy expenditure, including the arcuate nucleus of the hypothalamus. While obesity is known to disrupt neurocircuits controlling energy balance, including those in the hypothalamic arcuate nucleus, the pharmacological targeting of these central mechanisms often produces adverse cardiovascular and other off-target effects. This highlights the critical need to identify new anti-obesity drugs that can activate central neurocircuits to induce weight loss without negatively impacting blood pressure control. The renin–angiotensin system may provide this ideal target, as recent studies show this hormonal system can engage neurocircuits originating in the arcuate nucleus to improve energy balance without elevating blood pressure in animal models. This review will summarize the current knowledge of renin–angiotensin system actions within the arcuate nucleus for control of energy balance, with a focus on emerging roles for angiotensin II, prorenin, and angiotensin-(1–7) pathways.

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The renin–angiotensin system in the arcuate nucleus controls resting metabolic rate

Cited by 15 publications

References 62 publications

Interactions of the Brain Renin-Angiotensin-System (RAS) and Inflammation in the Sensitization of Hypertension

Interactions of the Brain Renin-Angiotensin-System (RAS) and Inflammation in the Sensitization of Hypertension

Hypothalamic Renin–Angiotensin System and Lipid Metabolism: Effects of Virgin Olive Oil versus Butter in the Diet

The Arcuate Nucleus of the Hypothalamus and Metabolic Regulation: An Emerging Role for Renin–Angiotensin Pathways

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