Topical menthol, a pharmacological cold mimic, induces cold sensitivity, adaptive thermogenesis and brown adipose tissue activation in mice.

Autor: Sankina P; Department of Anesthesiology, University Hospital Erlangen, Friedrich-Alexander-Universität, Erlangen, Germany., Lal R; TR(i)P for Health Laboratory, Centre for Excellence in Functional Foods, Department of Food and Nutritional Biotechnology, National Agri-Food Biotechnology Institute (NABI), Nagar, India.; University Institute of Pharmaceutical Sciences, Panjab University, Chandigarh, India., Khare P; Department of Anesthesiology, University Hospital Erlangen, Friedrich-Alexander-Universität, Erlangen, Germany.; Department of Pharmacy, Birla Institute of Technology and Science-Pilani, Pilani, India., von Hörsten S; Department of Experimental Therapy, University Hospital Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany., Fester L; Department of Anatomy and Cell Biology, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), Erlangen, Germany., Aggarwal V; Scott-Edil, Chandigarh, India., Zimmermann K; Department of Anesthesiology, University Hospital Erlangen, Friedrich-Alexander-Universität, Erlangen, Germany., Bishnoi M; Department of Anesthesiology, University Hospital Erlangen, Friedrich-Alexander-Universität, Erlangen, Germany.; TR(i)P for Health Laboratory, Centre for Excellence in Functional Foods, Department of Food and Nutritional Biotechnology, National Agri-Food Biotechnology Institute (NABI), Nagar, India.
Jazyk: angličtina
Zdroj: Diabetes, obesity & metabolism [Diabetes Obes Metab] 2024 Oct; Vol. 26 (10), pp. 4329-4345. Date of Electronic Publication: 2024 Jul 23.
DOI: 10.1111/dom.15781
Abstrakt: Aim: Brown adipose tissue (BAT) thermogenesis has profound energy-expanding potential, which makes it an attractive target tissue to combat ever-increasing obesity and its other associated metabolic complications. Although it is fairly accepted that cold is a potent inducer of BAT activation and function, there are limited studies on the mechanisms of pharmacological cold-mimicking agents, such as the TRPM8 agonist, menthol, on BAT thermogenesis and activation.
Methods: Herein, we sought to determine the effect of topical application of menthol (10% w/v [4 g/kg] cream formulation/day for 15 days) on temperature sensitivity behaviour (thermal gradient assay, nesting behaviour), adaptive thermogenesis (infrared thermography, core body temperature), BAT sympathetic innervation (tyrosine hydroxylase immunohistochemistry) and activation (18F-FDG PET-CT analysis, Uncoupling Protein 1 immunohistochemistry and BAT gene expression), whole-body energy expenditure (indirect calorimetry) and other metabolic variables in male C57BL/6N mice.
Results: We show that male C57BL/6N mice: (a) develop a warm-seeking and cold-avoiding thermal preference phenotype; (b) display increased locomotor activity and adaptive thermogenesis; (c) show augmented sympathetic innervation in BAT and its activation; (d) exhibit enhanced gluconeogenic capacity (increased glucose excursion in response to pyruvate) and insulin sensitivity; and (e) show enhanced whole-body energy expenditure and induced lipid-utilizing phenotype after topical menthol application.
Conclusions: Taken together, our findings highlight that pharmacological cold mimicking using topical menthol application presents a potential therapeutic strategy to counter weight gain and related complications.
(© 2024 The Author(s). Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.)
Databáze: MEDLINE
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