Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Bioavailable menthol (Transient Receptor Potential Melastatin-8 agonist) induces energy expending phenotype in differentiating adipocytes

Version 1 : Received: 31 December 2018 / Approved: 11 January 2019 / Online: 11 January 2019 (15:47:35 CET)

A peer-reviewed article of this Preprint also exists.

Khare, P.; Chauhan, A.; Kumar, V.; Kaur, J.; Mahajan, N.; Kumar, V.; Gesing, A.; Chopra, K.; Kondepudi, K.K.; Bishnoi, M. Bioavailable Menthol (Transient Receptor Potential Melastatin-8 Agonist) Induces Energy Expending Phenotype in Differentiating Adipocytes. Cells 2019, 8, 383. Khare, P.; Chauhan, A.; Kumar, V.; Kaur, J.; Mahajan, N.; Kumar, V.; Gesing, A.; Chopra, K.; Kondepudi, K.K.; Bishnoi, M. Bioavailable Menthol (Transient Receptor Potential Melastatin-8 Agonist) Induces Energy Expending Phenotype in Differentiating Adipocytes. Cells 2019, 8, 383.

Abstract

Recent evidences support a role of menthol, a TRPM8 agonist, in enhanced energy expenditure, thermogenesis and BAT-like activity in classical WAT depots in TRPM8 dependent and independent manner. The present study was designed to analyze whether oral and topical administration of menthol is bioavailable at subcutaneous adipose tissue and is sufficient to induce desired energy expenditure effects directly. GC-FID was performed to study menthol bioavailability in serum and subcutaneous white adipose tissue following oral and topical administration. Further, 3T3L1 adipocytes were treated with bioavailable menthol doses and different parameters (lipid accumulation, “browning/brite” and energy expenditure gene expression, metal analysis, mitochondrial complex’s gene expression) were studied. No difference was observed in serum levels but significant difference was seen in the menthol concentration on subcutaneous adipose tissues after oral and topical application. Menthol administration at bioavailable doses significantly increased “browning/brite” and energy expenditure phenotype, enhanced mitochondrial activity related gene expression, increased metal concentration but didn’t alter the lipid accumulation. Further, we used pharmacological antagonism based approach to study the TRPM8 involvement in menthol effect. In conclusion, the present study provides an evidence that bioavailable menthol after single oral and topical administration is sufficient to induce “brite” phenotype in subcutaneous adipose tissue.

Keywords

Adipose tissue, Bioavailable, Menthol, Topical, TRPM8.

Subject

Medicine and Pharmacology, Pharmacology and Toxicology

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