Titel: Puerariae lobatae root extracts and the regulation of brown fat activity
Sprache: Englisch
Autor*in: Buhlmann, Elisabeth
Schlagwörter: Asian herbs; Obesity; UCP1; Puerarin; Daidzein; Genistein
GND-Schlagwörter: Mitochondrial Uncoupling ProteinGND
Braunes FettgewebeGND
Erscheinungsdatum: 2023
Tag der mündlichen Prüfung: 2024-01-12
Background: Obesity is one of the major health problems worldwide. The induction of brown adipocyte formation and activity represents a promising therapeutic option by increasing energy expenditure. Asian herbs have the potential to treat obesity, however, pharmacological effects should be well documented at the molecular level first. Hypothesis: A novel hypothesis-driven screening approach identified the root of Pueraria montana var. lobata (Willd.) Sanjappa & Pradeep (PLR) to have potential effects on obesity by stimulating brown adipocytes. Study design: This study explored the metabolic effects of PLR water extract (PLRE) in a high-fat diet-induced obesity mouse model and characterized its secondary metabolite composition. Methods: Animals were orally treated daily for two weeks and the bioactivity of PLRE evaluated by measuring various parameters including body weight, circulating metabolites, energy expenditure and insulin sensitivity. The chemical composition of the mains components was obtained by HPLC–MS–ELSD–PDA. Based on the dereplication results and semi-quantitative estimation, pure molecules were selected for tests on adipocytes in vitro. Results: PLRE induces brown adipocyte activity and triggers the formation of brown-like cells in inguinal fat tissue, weight loss, and improved glucose metabolism. These effects are primarily caused by cell-autonomous activation of brown adipocytes and not by autonomic nervous system regulation. Even though the analysis of PLRE revealed puerarin as the most
abundant secondary metabolite, it showed no effect on brown adipocyte formation and function. Brown adipocyte activity was induced dose-dependently by two other isoflavones, daidzein, and genistein. Daidzein is present in a very small amount in PLRE, but various glycosidic isoflavones, including puerarin, may release
daidzein after metabolism. Conclusion: This approach demonstrated the positive effects of PLRE on a diet-induced obesity mouse model and provided clues on the mode of action of PLRE at the molecular level.
URL: https://ediss.sub.uni-hamburg.de/handle/ediss/10845
URN: urn:nbn:de:gbv:18-ediss-116868
Dokumenttyp: Dissertation
Betreuer*in: Heeren, Jörg
Enthalten in den Sammlungen:Elektronische Dissertationen und Habilitationen

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