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The action of p-synephrine on hepatic carbohydrate metabolism and respiration occurs via both Ca2+-mobilization and cAMP production

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Abstract

Citrus aurantium extracts, which contain large amounts of p-synephrine, are widely used for weight loss purposes and as appetite suppressants. In the liver, C. aurantium (bitter orange) extracts affect hemodynamics, carbohydrate metabolism, and oxygen uptake. The purpose of the present work was to quantify the action of p-synephrine and also to obtain indications about its mechanism of action, a task that would be difficult to accomplish with C. aurantium extracts due to their rather complex composition. The experimental system was the isolated perfused rat liver. p-Synephrine significantly stimulated glycogenolysis, glycolysis, gluconeogenesis, and oxygen uptake. The compound also increased the portal perfusion pressure and the redox state of the cytosolic NAD+/NADH couple. A Ca2+-dependency for both the hemodynamic and the metabolic effects of p-synephrine was found. p-Synephrine stimulated both cAMP overflow and the initial Ca2+ release from the cellular stores previously labeled with 45Ca2+. The metabolic and hemodynamic actions of p-synephrine were strongly inhibited by α-adrenergic antagonists and moderately affected by β-adrenergic antagonists. The results allow to conclude that p-synephrine presents important metabolic and hemodynamic effects in the liver. These effects can be considered as both catabolic (glycogenolysis) and anabolic (gluconeogenesis), they are mediated by both α- and β-adrenergic signaling, require the simultaneous participation of both Ca2+ and cAMP, and could be contributing to the overall stimulation of metabolism that usually occurs during weight loss periods.

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Acknowledgments

This work was supported by Grants from the Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq). Andrea Luiza de Oliveira is a fellowship holder of the Coordenação de Aperfeiçoamento de Pessoal do Ensino Superior (CAPES).

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Authors and Affiliations

  1. Department of Biochemistry, University of Maringá, Avenida Colombo 5790, Maringá, 87020900, Brazil

    Andrea Luiza de Oliveira, Jurandir Fernando Comar, Anacharis Babeto de Sá-Nakanishi, Rosane Marina Peralta & Adelar Bracht

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  1. Andrea Luiza de Oliveira
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  2. Jurandir Fernando Comar
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  3. Anacharis Babeto de Sá-Nakanishi
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Correspondence to Adelar Bracht.

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de Oliveira, A.L., Comar, J.F., de Sá-Nakanishi, A.B. et al. The action of p-synephrine on hepatic carbohydrate metabolism and respiration occurs via both Ca2+-mobilization and cAMP production. Mol Cell Biochem 388, 135–147 (2014). https://doi.org/10.1007/s11010-013-1905-2

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