Metabolic rate regulation by the renin–angiotensin system: brain vs. body

Grobe, Justin L; Rahmouni, Kamal; Liu, Xuebo

doi:10.1007/s00424-012-1096-9

Cited by 30 publications

(32 citation statements)

References 86 publications

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“…7). These studies were prompted by evidence for both leptin and angiotensin receptors in several brain regions involved in the regulation of SNA (141) and by mounting evidence that the brain RAS participates in the sympathetic regulation of energy expenditure and adiposity (46,47), as well as BP (23,46). Prompted by this background, we demonstrated that deletion of ANG II type 1a receptors (AT1aR) in mice and pharmacological blockade of brain AT1R in rats attenuated leptin-induced increases in renal and BAT SNA but did not alter effects of leptin on food intake.…”

mentioning

confidence: 99%

Selective leptin resistance revisited

Mark

2013

American Journal of Physiology-Regulatory, Integrative and Comp

142

118

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In addition to effects on appetite and metabolism, leptin influences many neuroendocrine and physiological systems, including the sympathetic nervous system. Building on my Carl Ludwig Lecture of the American Physiological Society, I review the sympathetic and cardiovascular actions of leptin. The review focuses on a critical analysis of the concept of selective leptin resistance (SLR) and the role of leptin in the pathogenesis of obesity-induced hypertension in both experimental animals and humans. We introduced the concept of SLR in 2002 to explain how leptin might increase blood pressure (BP) in obese states, such as diet-induced obesity (DIO), that are accompanied by partial leptin resistance. This concept, analogous to selective insulin resistance in the metabolic syndrome, holds that in several genetic and acquired models of obesity, there is preservation of the renal sympathetic and pressor actions of leptin despite attenuation of the appetite and weight-reducing actions. Two potential overlapping mechanisms of SLR are reviewed: 1) differential leptin molecular signaling pathways that mediate selective as opposed to universal leptin action and 2) brain site-specific leptin action and resistance. Although the phenomenon of SLR in DIO has so far focused on preservation of sympathetic and BP actions of leptin, consideration should be given to the possibility that this concept may extend to preservation of other actions of leptin. Finally, I review perplexing data on the effects of leptin on sympathetic activity and BP in humans and its role in human obesity-induced hypertension.

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confidence: 99%

Selective leptin resistance revisited

Mark

2013

American Journal of Physiology-Regulatory, Integrative and Comp

142

118

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“…The findings that 1) expression of Ren-a, which is dormant in brain of normal mice, was increased in Ren-b Null mice, and 2) Ren-a expression is increased and Ren-b expression is decreased in DOCA-salt hypertension suggested the possibility that this may occur naturally and play a regulatory role. 14 Based on a preponderance of the evidence, we hypothesize that 1) there is a tight selective transcriptional regulation of Ren-b and Ren-a, and 2) disinhibition of Ren-a may occur in response to physiological or pathophysiological cues. However, the molecular mechanism whereby Ren-a disinhibition occurs remains unclear.…”

Section: Discussionmentioning

confidence: 99%

“…Supporting this model, there is a switch in expression from primarily Ren-b in the brain of untreated wildtype mice to the expression of primarily Ren-a within the brain in response to DOCA-salt treatment. 14 This suggests a novel mechanism by which certain physiological cues causes a disinhibition of Ren-a.…”

Section: Introductionmentioning

confidence: 99%

Selective Deletion of Renin-b in the Brain Alters Drinking and Metabolism

et al. 2017

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The brain specific isoform of renin (Ren-b), has been proposed as a negative regulator of the brain renin-angiotensin system (RAS). We analyzed mice with a selective deletion of Ren-b which preserved expression of the classical renin (Ren-a) isoform. We reported that Ren-bNull mice exhibited central RAS activation and hypertension through increased expression of Ren-a, but the dipsogenic and metabolic effects in Ren-bNull mice are unknown. Fluid intake was similar in control and Ren-bNull mice at baseline and both exhibited an equivalent dipsogenic response to DOCA-salt. Dehydration promoted increased water intake in Ren-bNull mice, particularly after DOCA-salt. Ren-bNull and control mice exhibited similar body weight when fed a chow diet. However, when fed a high fat diet, male Ren-bNull mice gained significantly less weight than control mice, an effect blunted in females. This difference was not due to changes in food intake, energy absorption or physical activity. Ren-bNull mice exhibited increased resting metabolic rate concomitant with increased uncoupled protein 1 expression and sympathetic nerve activity to the interscapular brown adipose tissue (BAT), suggesting increased thermogenesis. Ren-bNull mice were modestly intolerant to glucose and had normal insulin sensitivity. Another mouse model with markedly enhanced brain RAS activity (sRA mice) exhibited pronounced insulin sensitivity concomitant with increased BAT glucose uptake. Altogether, these data support the hypothesis that the brain RAS regulates energy homeostasis by controlling resting metabolic rate, and that Ren-b deficiency increases brain RAS activity. Thus, the relative level of expression of Ren-b and Ren-a may control activity of the brain RAS.

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“…5 Furthermore, global deletion or pharmacologic inhibition of RAS components results in a lean phenotype with maintenance of low endogenous leptin levels. 6 On the other hand, chronic systemic leptin infusion increases plasma RAS components, and plasma and lung Ang converting enzyme (ACE) activity is decreased in leptin-deficient ob/ob mice. 7 In the central nervous system, leptin and Ang II type-1 receptors (AT 1 R) are co-localized in forebrain and hindbrain regions involved in cardiometabolic control (Figure).…”

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confidence: 99%

To Sensitize or Not to Sensitize

Arnold

2016

Hypertension

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Metabolic rate regulation by the renin–angiotensin system: brain vs. body

Cited by 30 publications

References 86 publications

Selective leptin resistance revisited

Selective leptin resistance revisited

Selective Deletion of Renin-b in the Brain Alters Drinking and Metabolism

To Sensitize or Not to Sensitize

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