The renin-angiotensin system in the arcuate nucleus controls resting metabolic rate.
Study Goal
The researchers aimed to investigate the role of the brain's renin-angiotensin system (RAS) in controlling resting metabolic rate (RMR) in response to a high-fat diet and other stimuli.
Results Summary
The study found that the angiotensin II Agtr1a receptor, localized to a specific subset of Agrp neurons in the arcuate nucleus, is required for stimulating thermogenic sympathetic activity and RMR in response to a high-fat diet, but not for suppressing food intake or increasing blood pressure.
Population
Not specified (likely animal models, given the focus on hypothalamic neurons).
Effective Dosage
Not mentioned
Duration
Not mentioned
Interactions
None mentioned
| Intervention | Direction | Endpoint | Population | Dosage | Impact | Claim # |
|---|---|---|---|---|---|---|
high-fat diet | increase | thermogenic sympathetic nervous activity and RMR | Agtr1a receptor colocalizing cells in ARC | - | stimulation | #1 |
deoxycorticosterone acetate and salt | increase | thermogenic sympathetic nervous activity and RMR | Agtr1a receptor colocalizing cells in ARC | - | stimulation | #2 |
leptin | increase | thermogenic sympathetic nervous activity and RMR | Agtr1a receptor colocalizing cells in ARC | - | stimulation | #3 |
Agtr1a receptors in Agrp neurons | increase | thermogenic sympathetic nervous activity and RMR | - | - | required for stimulation | #4 |
Agtr1a receptors in Agrp neurons | no change | food intake | - | - | not required for suppression | #5 |
Agtr1a receptors in Agrp neurons | no change | blood pressure | - | - | not required for increasing | #6 |
RAS within the ARC | neutral | RMR control | - | - | implicated specifically in | #7 |
Agtr1a localized to the SST3 subset of Agrp neurons | neutral | RMR control | - | - | implicated primarily through | #8 |
PURPOSE OF REVIEW: Obesity represents the primary challenge to improving cardiovascular health, and suppression of resting metabolic rate (RMR) is implicated in the maintenance of obesity. Increasing evidence supports a major role for the renin-angiotensin system (RAS) within the brain in the control of RMR. RECENT FINDINGS: The angiotensin II (ANG) Agtr1a receptor colocalizes with the leptin receptor (Lepr) primarily within cells of the arcuate nucleus (ARC) of the hypothalamus that also express Agouti-related peptide (Agrp). This sub-population of Agtr1a receptors is required for stimulation of thermogenic sympathetic nervous activity and RMR, but not the suppression of food intake or increasing blood pressure, in response to various stimuli including high-fat diet, deoxycorticosterone acetate and salt, and leptin. Agtr1a is localized to a specific subset (SST3) of Agrp neurons within the ARC. SUMMARY: The RAS within the ARC is implicated specifically in RMR control, primarily through Agtr1a localized to the SST3 subset of Agrp neurons. Ongoing research is focused on understanding the unique anatomical projections, neurotransmitter utilization, and signal transduction pathways of Agtr1a within this subset of neurons. Understanding these projections and molecular mechanisms may identify therapeutic targets for RMR and thus obesity, independent of blood pressure and appetite.