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

Pragyanshu Khare,Neha Mahajan,Jasleen Kaur,Kanwaljit Chopra,Adam Gesing,Aakriti Chauhan,Vijay Kumar,Vibhu Kumar,Mahendra Bishnoi,Kanthi Kiran Kondepudi

doi:10.3390/cells8050383

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.

Highlights

The imbalance between energy intake and energy expenditure is a well-known aspect of the escalating prevalence of obesity throughout the world as a major nutritional challenge [1,2]
TRPM8 receptor on adipose tissue isadministration not required and the effect this work, we could suggest that the presence of TRPM8 receptor on adipose tissue is not required and the effect is selective to the glucagon receptor present on adipose tissue, we may say that it is an indirect action of menthol on adipose tissue
Recent paper by Clemmemsen and colleagues suggested that icilin, a TRPM8 agonist, effect on brown adipose tissue (BAT) energy expenditure cannot be explained by direct effects of icilin on adipocytes suggesting indirect actions to increase thermogenesis, likely through induction of sympathetic tone [25]

Summary

Introduction

The imbalance between energy intake and energy expenditure is a well-known aspect of the escalating prevalence of obesity throughout the world as a major nutritional challenge [1,2]. Cells 2019, 8, 383 factors like physical activity, dietary energy intake, basal metabolic rate, variation in environmental and body temperature are reported to influence energy expenditure [3,4]. Enhancement of energy expenditure is one of the cardinal approach toward prevention of body weight gain and obesity [5]. Numerous studies have reported the direct relation of cold exposure with non-shivering thermogenesis, followed by reduction in body fat [6,7,8]. Clinical studies have reported a vital link between cold-exposure and elevated energy expenditure through adaptive thermogenesis [9]. Studies on adipocytes have reported a relationship between cold receptor, TRPM8 and energy expenditure showing upregulated expression of UCP-1 and PGC-1α owing to TRPM8 activation [10]

Methods

Results

Discussion

Conclusion