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Cells. 2019 Apr 26;8(5). pii: E383. doi: 10.3390/cells8050383.

Bioavailable Menthol (Transient Receptor Potential Melastatin-8 Agonist) Induces Energy Expending Phenotype in Differentiating Adipocytes.

Author information

1
National Agri-Food Biotechnology Institute (NABI), Knowledge City-Sector 81, SAS Nagar, Punjab 140603, India. khare.pragyanshu@gmail.com.
2
Pharmacology Division, University Institute of Pharmaceutical Sciences (UIPS), Panjab University, Chandigarh 160014, India. khare.pragyanshu@gmail.com.
3
Department of Pharmacology & Toxicology, National Institute of Pharmaceutical Education and Research (NIPER)-Raebareli, Transit campus Lucknow, Uttar Pradesh 226301, India. khare.pragyanshu@gmail.com.
4
National Agri-Food Biotechnology Institute (NABI), Knowledge City-Sector 81, SAS Nagar, Punjab 140603, India. chauhanaakriti11@gmail.com.
5
National Agri-Food Biotechnology Institute (NABI), Knowledge City-Sector 81, SAS Nagar, Punjab 140603, India. vibhu.kumar99@gmail.com.
6
National Agri-Food Biotechnology Institute (NABI), Knowledge City-Sector 81, SAS Nagar, Punjab 140603, India. jasleen.820@gmail.com.
7
National Agri-Food Biotechnology Institute (NABI), Knowledge City-Sector 81, SAS Nagar, Punjab 140603, India. mahajan23neha@gmail.com.
8
Regional Centre for Biotechnology, Faridabad-Gurgaon expressway, Faridabad, Haryana 121001, India. mahajan23neha@gmail.com.
9
National Agri-Food Biotechnology Institute (NABI), Knowledge City-Sector 81, SAS Nagar, Punjab 140603, India. 2210.vijay@gmail.com.
10
Department of Biotechnology, Panjab University, Sector-25, Chandigarh 160014, India. 2210.vijay@gmail.com.
11
Department of Endocrinology of Ageing, Medical University of Lodz, Zeligowski St, No 7/9, 90-752 Lodz, Poland. adges7@yahoo.com.
12
Pharmacology Division, University Institute of Pharmaceutical Sciences (UIPS), Panjab University, Chandigarh 160014, India. dr_chopra_k@yahoo.com.
13
National Agri-Food Biotechnology Institute (NABI), Knowledge City-Sector 81, SAS Nagar, Punjab 140603, India. kiran@nabi.res.in.
14
National Agri-Food Biotechnology Institute (NABI), Knowledge City-Sector 81, SAS Nagar, Punjab 140603, India. mbishnoi@nabi.res.in.

Abstract

Recent evidence supports the role of menthol, a TRPM8 agonist, in enhanced energy expenditure, thermogenesis and BAT-like activity in classical WAT depots in a TRPM8 dependent and independent manner. The present study was designed to analyse whether oral and topical administration of menthol is bioavailable at subcutaneous adipose tissue and is sufficient to directlyinduce desired energy expenditure effects. 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 during adipogenesis but did not alter the lipid accumulation as well as acute experiments were performed with lower dose of menthol on mature adipocytes In conclusion, the present study provides evidence that bioavailable menthol after single oral and topical administration is sufficient to induce "brite" phenotype in subcutaneous adipose tissue However, critical dose characterization for its clinical utility is required.

KEYWORDS:

TRPM8; adipose tissue; bioavailable; menthol; topical

PMID:
31027377
PMCID:
PMC6562930
DOI:
10.3390/cells8050383
[Indexed for MEDLINE]
Free PMC Article

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