The TRPM2 ion channel regulates metabolic and thermogenic adaptations in adipose tissue of cold-exposed mice
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The TRPM2 ion channel regulates metabolic and thermogenic adaptations in adipose tissue of cold-exposed mice. / Benzi, Andrea; Heine, Markus; Spinelli, Sonia; Salis, Annalisa; Worthmann, Anna; Diercks, Björn; Astigiano, Cecilia; Pérez Mato, Raúl; Memushaj, Adela; Sturla, Laura; Vellone, Valerio; Damonte, Gianluca; Jaeckstein, Michelle Y; Koch-Nolte, Friedrich; Mittrücker, Hans-Willi; Guse, Andreas H; De Flora, Antonio; Heeren, Joerg; Bruzzone, Santina.
in: FRONT ENDOCRINOL, Jahrgang 14, 2024, S. 1251351.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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T1 - The TRPM2 ion channel regulates metabolic and thermogenic adaptations in adipose tissue of cold-exposed mice
AU - Benzi, Andrea
AU - Heine, Markus
AU - Spinelli, Sonia
AU - Salis, Annalisa
AU - Worthmann, Anna
AU - Diercks, Björn
AU - Astigiano, Cecilia
AU - Pérez Mato, Raúl
AU - Memushaj, Adela
AU - Sturla, Laura
AU - Vellone, Valerio
AU - Damonte, Gianluca
AU - Jaeckstein, Michelle Y
AU - Koch-Nolte, Friedrich
AU - Mittrücker, Hans-Willi
AU - Guse, Andreas H
AU - De Flora, Antonio
AU - Heeren, Joerg
AU - Bruzzone, Santina
N1 - Copyright © 2023 Benzi, Heine, Spinelli, Salis, Worthmann, Diercks, Astigiano, Pérez Mato, Memushaj, Sturla, Vellone, Damonte, Jaeckstein, Koch-Nolte, Mittrücker, Guse, De Flora, Heeren and Bruzzone.
PY - 2024
Y1 - 2024
N2 - INTRODUCTION: During thermogenesis, adipose tissue (AT) becomes more active and enhances oxidative metabolism. The promotion of this process in white AT (WAT) is called "browning" and, together with the brown AT (BAT) activation, is considered as a promising approach to counteract obesity and metabolic diseases. Transient receptor potential cation channel, subfamily M, member 2 (TRPM2), is an ion channel that allows extracellular Ca2+ influx into the cytosol, and is gated by adenosine diphosphate ribose (ADPR), produced from NAD+ degradation. The aim of this study was to investigate the relevance of TRPM2 in the regulation of energy metabolism in BAT, WAT, and liver during thermogenesis.METHODS: Wild type (WT) and Trpm2-/- mice were exposed to 6°C and BAT, WAT and liver were collected to evaluate mRNA, protein levels and ADPR content. Furthermore, O2 consumption, CO2 production and energy expenditure were measured in these mice upon thermogenic stimulation. Finally, the effect of the pharmacological inhibition of TRPM2 was assessed in primary adipocytes, evaluating the response upon stimulation with the β-adrenergic receptor agonist CL316,243.RESULTS: Trpm2-/- mice displayed lower expression of browning markers in AT and lower energy expenditure in response to thermogenic stimulus, compared to WT animals. Trpm2 gene overexpression was observed in WAT, BAT and liver upon cold exposure. In addition, ADPR levels and mono/poly-ADPR hydrolases expression were higher in mice exposed to cold, compared to control mice, likely mediating ADPR generation.DISCUSSION: Our data indicate TRPM2 as a fundamental player in BAT activation and WAT browning. TRPM2 agonists may represent new pharmacological strategies to fight obesity.
AB - INTRODUCTION: During thermogenesis, adipose tissue (AT) becomes more active and enhances oxidative metabolism. The promotion of this process in white AT (WAT) is called "browning" and, together with the brown AT (BAT) activation, is considered as a promising approach to counteract obesity and metabolic diseases. Transient receptor potential cation channel, subfamily M, member 2 (TRPM2), is an ion channel that allows extracellular Ca2+ influx into the cytosol, and is gated by adenosine diphosphate ribose (ADPR), produced from NAD+ degradation. The aim of this study was to investigate the relevance of TRPM2 in the regulation of energy metabolism in BAT, WAT, and liver during thermogenesis.METHODS: Wild type (WT) and Trpm2-/- mice were exposed to 6°C and BAT, WAT and liver were collected to evaluate mRNA, protein levels and ADPR content. Furthermore, O2 consumption, CO2 production and energy expenditure were measured in these mice upon thermogenic stimulation. Finally, the effect of the pharmacological inhibition of TRPM2 was assessed in primary adipocytes, evaluating the response upon stimulation with the β-adrenergic receptor agonist CL316,243.RESULTS: Trpm2-/- mice displayed lower expression of browning markers in AT and lower energy expenditure in response to thermogenic stimulus, compared to WT animals. Trpm2 gene overexpression was observed in WAT, BAT and liver upon cold exposure. In addition, ADPR levels and mono/poly-ADPR hydrolases expression were higher in mice exposed to cold, compared to control mice, likely mediating ADPR generation.DISCUSSION: Our data indicate TRPM2 as a fundamental player in BAT activation and WAT browning. TRPM2 agonists may represent new pharmacological strategies to fight obesity.
KW - Mice
KW - Animals
KW - TRPM Cation Channels/genetics
KW - Adipose Tissue, Brown/metabolism
KW - Adipose Tissue, White/metabolism
KW - Obesity/genetics
KW - Thermogenesis/genetics
U2 - 10.3389/fendo.2023.1251351
DO - 10.3389/fendo.2023.1251351
M3 - SCORING: Journal article
C2 - 38390373
VL - 14
SP - 1251351
JO - FRONT ENDOCRINOL
JF - FRONT ENDOCRINOL
SN - 1664-2392
ER -
