Dataset Information

The brain Renin-angiotensin system controls divergent efferent mechanisms to regulate fluid and energy balance.

ABSTRACT: The renin-angiotensin system (RAS), in addition to its endocrine functions, plays a role within individual tissues such as the brain. The brain RAS is thought to control blood pressure through effects on fluid intake, vasopressin release, and sympathetic nerve activity (SNA), and may regulate metabolism through mechanisms which remain undefined. We used a double-transgenic mouse model that exhibits brain-specific RAS activity to examine mechanisms contributing to fluid and energy homeostasis. The mice exhibit high fluid turnover through increased adrenal steroids, which is corrected by adrenalectomy and attenuated by mineralocorticoid receptor blockade. They are also hyperphagic but lean because of a marked increase in body temperature and metabolic rate, mediated by increased SNA and suppression of the circulating RAS. ?-adrenergic blockade or restoration of circulating angiotensin-II, but not adrenalectomy, normalized metabolic rate. Our data point to contrasting mechanisms by which the brain RAS regulates fluid intake and energy expenditure.

SUBMITTER: Grobe JL

PROVIDER: S-EPMC2994017 | biostudies-literature | 2010 Nov

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

The brain Renin-angiotensin system controls divergent efferent mechanisms to regulate fluid and energy balance.

Grobe Justin L JL Grobe Connie L CL Beltz Terry G TG Westphal Scott G SG Morgan Donald A DA Xu Di D de Lange Willem J WJ Li Huiping H Sakai Koji K Thedens Daniel R DR Cassis Lisa A LA Rahmouni Kamal K Mark Allyn L AL Johnson Alan Kim AK Sigmund Curt D CD

Cell metabolism 20101101 5

The renin-angiotensin system (RAS), in addition to its endocrine functions, plays a role within individual tissues such as the brain. The brain RAS is thought to control blood pressure through effects on fluid intake, vasopressin release, and sympathetic nerve activity (SNA), and may regulate metabolism through mechanisms which remain undefined. We used a double-transgenic mouse model that exhibits brain-specific RAS activity to examine mechanisms contributing to fluid and energy homeostasis. Th ...[more]

PMID: 21035755

Similar Datasets

Project description:UNLABELLED:Astrocytes are well established modulators of extracellular glutamate, but their direct influence on energy balance-relevant behaviors is largely understudied. As the anorectic effects of glucagon-like peptide-1 receptor (GLP-1R) agonists are partly mediated by central modulation of glutamatergic signaling, we tested the hypothesis that astrocytic GLP-1R signaling regulates energy balance in rats. Central or peripheral administration of a fluorophore-labeled GLP-1R agonist, exendin-4, localizes within astrocytes and neurons in the nucleus tractus solitarius (NTS), a hindbrain nucleus critical for energy balance control. This effect is mediated by GLP-1R, as the uptake of systemically administered fluorophore-tagged exendin-4 was blocked by central pretreatment with the competitive GLP-1R antagonist exendin-(9-39). Ex vivo analyses show prolonged exendin-4-induced activation (live cell calcium signaling) of NTS astrocytes and neurons; these effects are also attenuated by exendin-(9-39), indicating mediation by the GLP-1R. In vitro analyses show that the application of GLP-1R agonists increases cAMP levels in astrocytes. Immunohistochemical analyses reveal that endogenous GLP-1 axons form close synaptic apposition with NTS astrocytes. Finally, pharmacological inhibition of NTS astrocytes attenuates the anorectic and body weight-suppressive effects of intra-NTS GLP-1R activation. Collectively, data demonstrate a role for NTS astrocytic GLP-1R signaling in energy balance control. SIGNIFICANCE STATEMENT:Glucagon-like peptide-1 receptor (GLP-1R) agonists reduce food intake and are approved by the Food and Drug Administration for the treatment of obesity, but the cellular mechanisms underlying the anorectic effects of GLP-1 require further investigation. Astrocytes represent a major cellular population in the CNS that regulates neurotransmission, yet the role of astrocytes in mediating energy balance is largely unstudied. The current data provide novel evidence that astrocytes within the NTS are relevant for energy balance control by GLP-1 signaling. Here, we report that GLP-1R agonists activate and internalize within NTS astrocytes, while behavioral data suggest the pharmacological relevance of NTS astrocytic GLP-1R activation for food intake and body weight. These findings support a previously unknown role for CNS astrocytes in energy balance control by GLP-1 signaling.

Dataset Information

The brain Renin-angiotensin system controls divergent efferent mechanisms to regulate fluid and energy balance.

Publications

The brain Renin-angiotensin system controls divergent efferent mechanisms to regulate fluid and energy balance.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets