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Updated: Jul 19, 2026
Arteriovenous Metabolomics to Measure In Vivo Metabolite Exchange in Brown Adipose Tissue
Published on: October 6, 2023
Hypermetabolism of fat in V1a vasopressin receptor knockout mice
Masami Hiroyama1, Toshinori Aoyagi, Yoko Fujiwara
1Department of Pharmacology, National Research Institute for Child Health and Development, 2-10-1 Okura, Setagaya-ku, Tokyo 157-8535, Japan.
Abstract:
[Arg8]Vasopressin (AVP) has an antilipolytic action on adipocytes, but little is known about the mechanisms involved. Here, we examined the involvement of the V1a receptor in the antilipolytic effect of AVP using V1a receptor-deficient (V1aR-/-) mice. The levels of blood glycerol were increased in V1aR-/- mice. The levels of ketone bodies, such as acetoacetic acid and 3-hydroxybutyric acid, the products of the lipid metabolism, were increased in V1aR-/- mice under a fasting condition. Triacylglyceride and free fatty acid levels in blood were decreased in V1aR-/- mice. Furthermore, measurements with tandem mass spectrometry determined that carnitine and acylcarnitines in serum, the products of beta-oxidation, were increased in V1aR-/- mice. Most acylcarnitines were increased in V1aR-/- mice, especially in the case of 2-carbon (C2), C10:1, C10, C14:1, C16, C18:1, and hydroxy-18:1-carbon (OH-C18:1)-acylcarnitines under feeding rather than under fasting conditions. The analysis of tissue C2-acylcarnitine level showed that beta-oxidation was promoted in muscle under the feeding condition and in liver under the fasting condition. An in vitro assay using brown adipocytes showed that the cells of V1aR-/- mice were more sensitive to isoproterenol for lipolysis. These results suggest that the lipid metabolism is enhanced in V1aR-/- mice. The cAMP level was enhanced in V1aR-/- mice in response to isoproterenol. The phosphorylation of Akt by insulin stimulation was reduced in V1aR-/- mice. These results suggest that insulin signaling is suppressed in V1aR-/- mice. In addition, the total bile acid, taurine, and cholesterol levels in blood were increased, and an enlargement of the cholecyst was observed in V1aR-/- mice. These results indicated that the production of bile acid was enhanced by the increased level of cholesterol and taurine. Therefore, these results indicated that AVP could modulate the lipid metabolism by the antilipolytic action and the synthesis of bile acid via the V1a receptor.
Insights
Arginine vasopressin (AVP) influences lipid metabolism via the V1a receptor. V1a receptor-deficient mice show enhanced lipid metabolism and bile acid production, suggesting AVP
Area of Science:
- Metabolic Physiology
- Endocrinology
- Lipid Metabolism
Background:
- [Arginine8]Vasopressin (AVP) exerts antilipolytic effects on adipocytes, but the underlying mechanisms, particularly the role of the V1a receptor, remain incompletely understood.
- Investigating the V1a receptor's function is crucial for understanding AVP's broader impact on metabolic regulation.
Purpose of the Study:
- To elucidate the role of the V1a receptor in mediating the antilipolytic effects of AVP.
- To investigate the impact of V1a receptor deficiency on lipid metabolism and related pathways in mice.
Main Methods:
- Utilized V1a receptor-deficient (V1aR-/-) mice to assess AVP's mechanism of action.
- Analyzed blood and tissue levels of glycerol, ketone bodies, triacylglycerides, free fatty acids, carnitine, and acylcarnitines using tandem mass spectrometry.
- Conducted in vitro assays with brown adipocytes and examined insulin signaling pathways.
Main Results:
- V1aR-/- mice exhibited increased blood glycerol, ketone bodies, carnitine, and acylcarnitines, indicating enhanced lipid metabolism and beta-oxidation.
- Lipolysis in V1aR-/- brown adipocytes was more sensitive to isoproterenol, with elevated cAMP levels.
- Insulin signaling, evidenced by Akt phosphorylation, was reduced in V1aR-/- mice, alongside increased bile acid, taurine, and cholesterol levels.
Conclusions:
- AVP modulates lipid metabolism through V1a receptor-mediated antilipolytic actions.
- V1a receptor deficiency enhances lipid metabolism and bile acid synthesis, potentially via altered insulin signaling.
- These findings highlight the V1a receptor's significant role in regulating systemic lipid homeostasis.
