Rapid modulation of interscapular brown adipose tissue mitochondrial activity by ketosis induced by 1,3-butanediol administration to rats.

Autor: Venditti P; Department of Biology, University of Naples Federico II, Complesso Monte Sant'Angelo, Naples, Italy., Pinto G; Department of Chemical Sciences, University of Naples Federico II, Complesso Monte Sant'Angelo, Naples, Italy., Migliaccio V; Department of Chemistry and Biology 'A. Zambelli', University of Salerno, Fisciano, Italy., Panico G; Department of Biology, University of Naples Federico II, Complesso Monte Sant'Angelo, Naples, Italy., Fasciolo G; Department of Biology, University of Naples Federico II, Complesso Monte Sant'Angelo, Naples, Italy., De Matteis R; Department of Biomolecular Sciences, University of Urbino Carlo Bo, Urbino, Italy., Lionetti L; Department of Chemistry and Biology 'A. Zambelli', University of Salerno, Fisciano, Italy., de Lange P; Department of Environmental, Biological, and Pharmaceutical Sciences and Technologies, University of Campania 'Luigi Vanvitelli', Caserta, Italy., Serpico S; Department of Chemical Sciences, University of Naples Federico II, Complesso Monte Sant'Angelo, Naples, Italy., Napolitano G; Department of Science and Technology, Parthenope University of Naples, Naples, Italy., Agnisola C; Department of Biology, University of Naples Federico II, Complesso Monte Sant'Angelo, Naples, Italy., Amoresano A; Department of Chemical Sciences, University of Naples Federico II, Complesso Monte Sant'Angelo, Naples, Italy.; Consorzio Interuniversitario Istituto Nazionale Biostrutture e Biosistemi - INBB, Rome, Italy., Lombardi A; Department of Biology, University of Naples Federico II, Complesso Monte Sant'Angelo, Naples, Italy.
Jazyk: angličtina
Zdroj: FASEB journal : official publication of the Federation of American Societies for Experimental Biology [FASEB J] 2024 Nov 30; Vol. 38 (22), pp. e70195.
DOI: 10.1096/fj.202401592RR
Abstrakt: Some studies indicate that brown adipose tissue (BAT) represents a promising target in the fight against dysmetabolic diseases, with indications suggesting it as a potential target for the effects of ketone bodies. We investigate whether the elevation of plasma levels of the ketone body β-hydroxybutyrate, achieved through the in vivo administration of its precursor 1,3-butanediol (BD) to rats, could impact interscapular BAT (iBAT) mitochondrial biochemistry and functionality. We examined the effects induced by BD within 3 h and after 2 weeks of treatment. A large-scale quantitative proteomics approach, coupling liquid chromatography with tandem mass spectrometry (LC-MS/MS) analysis, and Western blot associated with functional studies by respirometry allowed us to evaluate the changes in iBAT mitochondrial protein expression and bioenergetics induced by BD. BD administration increased β-hydroxybutyrate plasma levels, which correlated with an enhancement in iBAT mitochondrial respiration rate, likely due to the activation of the respiratory chain and uncoupling protein-1. The proteomic analysis demonstrated that BD influenced the mitochondrial levels of specific subunits belonging to the five respiratory complexes, uncoupling protein-1, and proteins involved in propanoate metabolism. BD administration also induced lysine β-hydroxybutyrylation of mitochondrial proteins, including specific subunits of the respiratory chain complexes and uncoupling protein-1. Most of the BD-induced effects were observed within 3 h of its administration and persisted/increased after 2 weeks of treatment. In conclusion, by using BD to increase β-hydroxybutyrate levels, we provide evidence supporting the role of β-hydroxybutyrate as a signaling molecule capable of rapidly modulating BAT physiology by acting at the mitochondrial level.
(© 2024 The Author(s). The FASEB Journal published by Wiley Periodicals LLC on behalf of Federation of American Societies for Experimental Biology.)
Databáze: MEDLINE
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