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Enhanced browning of adipose tissue by mirabegron-microspheres.
Niu, Zheming; Hildebrand, Staffan; Kappes, Sebastian; Ali, Mohamed Ehab; Vogel, Matthias; Mikhael, Mickel; Ran, Danli; Kozak, Jan; Wiedner, Maria; Richter, Dirk F; Lamprecht, Alf; Pfeifer, Alexander.
Afiliación
  • Niu Z; Institute of Pharmacology and Toxicology, University Hospital, University of Bonn, Bonn, Germany.
  • Hildebrand S; Institute of Pharmacology and Toxicology, University Hospital, University of Bonn, Bonn, Germany.
  • Kappes S; Department of Pharmaceutics, Institute of Pharmacy, University of Bonn, Bonn, Germany.
  • Ali ME; Department of Pharmaceutics, Institute of Pharmacy, University of Bonn, Bonn, Germany.
  • Vogel M; Pharmacogenomic, Federal Institute for Drugs and Medical Devices (BfArM), Bonn, Germany.
  • Mikhael M; Institute of Pharmacology and Toxicology, University Hospital, University of Bonn, Bonn, Germany.
  • Ran D; Institute of Pharmacology and Toxicology, University Hospital, University of Bonn, Bonn, Germany.
  • Kozak J; Department of Pharmaceutics, Institute of Pharmacy, University of Bonn, Bonn, Germany.
  • Wiedner M; Institut ID, Beethoven Clinic, Plastic and Aesthetic Surgery Cologne, Cologne, Germany.
  • Richter DF; Institut ID, Beethoven Clinic, Plastic and Aesthetic Surgery Cologne, Cologne, Germany.
  • Lamprecht A; Department of Pharmaceutics, Institute of Pharmacy, University of Bonn, Bonn, Germany. Electronic address: alf.lamprecht@uni-bonn.de.
  • Pfeifer A; Institute of Pharmacology and Toxicology, University Hospital, University of Bonn, Bonn, Germany. Electronic address: alexander.pfeifer@uni-bonn.de.
J Control Release ; 2024 Sep 13.
Article en En | MEDLINE | ID: mdl-39278357
ABSTRACT
Thermogenic brown adipose tissue (BAT) has emerged as an attractive target for combating obesity. However, pharmacological activation of energy expenditure by BAT and/or induction of browning of white adipose tissue (WAT) has been hampered by cardiovascular side effects. To address these concerns, we developed polylactide-co-glycolide acid (PLGA) microspheres loaded with mirabegron (MIR), a selective beta-3 adrenergic receptor (ADRB3) agonist, to achieve sustained local induction and activation of thermogenic adipocytes. MIR-loaded PLGA microspheres (MIR-MS) effectively activated brown adipocytes and enhanced the thermogenic program in white adipocytes. Moreover, treating isolated inguinal WAT (iWAT) with MIR-MS resulted in increased expression of browning markers and elevated lipolysis mainly via ADRB3. In mice, injection of MIR-MS over four weeks induced browning of iWAT at the injection site. Importantly, local MIR-MS injection successfully mitigated unwanted cardiovascular risks, including high systolic blood pressure (SBP) and heart rate, as compared to MIR-treated mice. Finally, injecting MIR-MS into human subcutaneous WAT led to a significant induction of lipolysis and an increase in the expression of thermogenic marker uncoupling protein 1 (UCP1). Taken together, our findings indicate that MIR-MS function as a local drug release system that induces browning of human and murine subcutaneous WAT while mitigating undesirable cardiovascular effects.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: J Control Release Asunto de la revista: FARMACOLOGIA Año: 2024 Tipo del documento: Article País de afiliación: Alemania Pais de publicación: Países Bajos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: J Control Release Asunto de la revista: FARMACOLOGIA Año: 2024 Tipo del documento: Article País de afiliación: Alemania Pais de publicación: Países Bajos