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

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.

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

Cells ◽

10.3390/cells8050383 ◽

2019 ◽

Vol 8 (5) ◽

pp. 383 ◽

Cited By ~ 4

Author(s):

Pragyanshu Khare ◽

Aakriti Chauhan ◽

Vibhu Kumar ◽

Jasleen Kaur ◽

Neha Mahajan ◽

...

Keyword(s):

Gene Expression ◽

Adipose Tissue ◽

Energy Expenditure ◽

Lipid Accumulation ◽

Subcutaneous Adipose Tissue ◽

Transient Receptor Potential ◽

Topical Administration ◽

Transient Receptor Potential Melastatin ◽

Significant Difference ◽

Subcutaneous Adipose

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.

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DNA methylation in adipocytes from visceral and subcutaneous adipose tissue influences insulin-signaling gene expression in obese individuals

International Journal of Obesity ◽

10.1038/s41366-020-00729-7 ◽

2021 ◽

Author(s):

Aneta Cierzniak ◽

Dorota Pawelka ◽

Krzysztof Kaliszewski ◽

Jerzy Rudnicki ◽

Tadeusz Dobosz ◽

...

Keyword(s):

Gene Expression ◽

Dna Methylation ◽

Adipose Tissue ◽

Insulin Signaling ◽

Subcutaneous Adipose Tissue ◽

Subcutaneous Adipose

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Adiponectin gene expression and adipocyte diameter: a comparison between epicardial and subcutaneous adipose tissue in men

Cardiovascular Pathology ◽

10.1016/j.carpath.2010.07.005 ◽

2011 ◽

Vol 20 (5) ◽

pp. e153-e156 ◽

Cited By ~ 62

Author(s):

Clara Bambace ◽

Mariassunta Telesca ◽

Elena Zoico ◽

Anna Sepe ◽

Debora Olioso ◽

...

Keyword(s):

Gene Expression ◽

Adipose Tissue ◽

Subcutaneous Adipose Tissue ◽

Adiponectin Gene ◽

Subcutaneous Adipose

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460 Effect of Different Fatty Acid Profiles in the Maternal and Finishing Diet on Subcutaneous Adipose Tissue Fatty Acid Profile and Gene Expression.

Journal of Animal Science ◽

10.1093/jas/sky073.457 ◽

2018 ◽

Vol 96 (suppl_2) ◽

pp. 247-247 ◽

Cited By ~ 2

Author(s):

D N Coleman ◽

A C Carranza Martin ◽

A E Relling

Keyword(s):

Gene Expression ◽

Adipose Tissue ◽

Fatty Acid ◽

Fatty Acid Profile ◽

Subcutaneous Adipose Tissue ◽

Fatty Acid Profiles ◽

Adipose Tissue Fatty Acid ◽

Tissue Fatty Acid ◽

Subcutaneous Adipose

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Thermogenic response to epinephrine in the forearm and abdominal subcutaneous adipose tissue

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.1992.263.5.e850 ◽

1992 ◽

Vol 263 (5) ◽

pp. E850-E855 ◽

Cited By ~ 13

Author(s):

L. Simonsen ◽

J. Bulow ◽

J. Madsen ◽

N. J. Christensen

Keyword(s):

Skeletal Muscle ◽

Adipose Tissue ◽

Energy Expenditure ◽

Oxygen Uptake ◽

Glucose Uptake ◽

Subcutaneous Adipose Tissue ◽

Whole Body ◽

Epinephrine Infusion ◽

Basal Period ◽

Subcutaneous Adipose

Whole body energy expenditure, thermogenic and metabolic changes in the forearm, and intercellular glucose concentrations in subcutaneous adipose tissue on the abdomen determined by microdialysis were measured during epinephrine infusion in healthy subjects. After a control period, epinephrine was infused at rates of 0.2 and 0.4 nmol.kg-1 x min-1. Whole body resting energy expenditure was 4.36 +/- 0.56 (SD) kJ/min. Energy expenditure increased to 5.14 +/- 0.74 and 5.46 +/- 0.79 kJ/min, respectively (P < 0.001), during the epinephrine infusions. Respiratory exchange ratio was 0.80 +/- 0.04 in the resting state and did not change. Local forearm oxygen uptake was 3.9 +/- 1.3 mumol.100 g-1 x min-1 in the basal period. During epinephrine infusion, it increased to 5.8 +/- 2.1 (P < 0.03) and 7.5 +/- 2.3 mumol.100 g-1 x min-1 (P < 0.001). Local forearm glucose uptake was 0.160 +/- 0.105 mumol.100 g-1 x min-1 and increased to 0.586 +/- 0.445 and 0.760 +/- 0.534 mumol.100 g-1 x min-1 (P < 0.025). The intercellular glucose concentration in the subcutaneous adipose tissue on the abdomen was equal to the arterial concentration in the basal period but did not increase as much during infusion of epinephrine, indicating glucose uptake in adipose tissue in this condition. If it is assumed that forearm skeletal muscle is representative for the average skeletal muscle, it can be calculated that on average 40% of the enhanced whole body oxygen uptake induced by infusion of epinephrine is taking place in skeletal muscle. It is proposed that adipose tissue may contribute to epinephrine-induced thermogenesis.

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Gene Expression of FTO in Human Subcutaneous Adipose Tissue, Peripheral Blood Mononuclear Cells and Adipocyte Cell Line

Journal of Nutrigenetics and Nutrigenomics ◽

10.1159/000320732 ◽

2010 ◽

Vol 3 (1) ◽

pp. 37-45 ◽

Cited By ~ 18

Author(s):

Tiina Lappalainen ◽

Marjukka Kolehmainen ◽

Ursula Schwab ◽

Leena Pulkkinen ◽

Vanessa D.F. de Mello ◽

...

Keyword(s):

Gene Expression ◽

Adipose Tissue ◽

Peripheral Blood Mononuclear Cells ◽

Peripheral Blood ◽

Subcutaneous Adipose Tissue ◽

Mononuclear Cells ◽

Peripheral Blood Mononuclear ◽

Blood Mononuclear Cells ◽

Adipocyte Cell ◽

Subcutaneous Adipose

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Assessing the Contribution of Relative Macrophage Frequencies to Subcutaneous Adipose Tissue

Frontiers in Nutrition ◽

10.3389/fnut.2021.675935 ◽

2021 ◽

Vol 8 ◽

Author(s):

Marianthi Kalafati ◽

Michael Lenz ◽

Gökhan Ertaylan ◽

Ilja C. W. Arts ◽

Chris T. Evelo ◽

...

Keyword(s):

Gene Expression ◽

Adipose Tissue ◽

Subcutaneous Adipose Tissue ◽

Tissue Cell ◽

Cell Type ◽

Expression Of Genes ◽

Cell Type Composition ◽

Type Composition ◽

Adipose Tissue Cell ◽

Subcutaneous Adipose

Background: Macrophages play an important role in regulating adipose tissue function, while their frequencies in adipose tissue vary between individuals. Adipose tissue infiltration by high frequencies of macrophages has been linked to changes in adipokine levels and low-grade inflammation, frequently associated with the progression of obesity. The objective of this project was to assess the contribution of relative macrophage frequencies to the overall subcutaneous adipose tissue gene expression using publicly available datasets.Methods: Seven publicly available microarray gene expression datasets from human subcutaneous adipose tissue biopsies (n = 519) were used together with TissueDecoder to determine the adipose tissue cell-type composition of each sample. We divided the subjects in four groups based on their relative macrophage frequencies. Differential gene expression analysis between the high and low relative macrophage frequencies groups was performed, adjusting for sex and study. Finally, biological processes were identified using pathway enrichment and network analysis.Results: We observed lower frequencies of adipocytes and higher frequencies of adipose stem cells in individuals characterized by high macrophage frequencies. We additionally studied whether, within subcutaneous adipose tissue, interindividual differences in the relative frequencies of macrophages were reflected in transcriptional differences in metabolic and inflammatory pathways. Adipose tissue of individuals with high macrophage frequencies had a higher expression of genes involved in complement activation, chemotaxis, focal adhesion, and oxidative stress. Similarly, we observed a lower expression of genes involved in lipid metabolism, fatty acid synthesis, and oxidation and mitochondrial respiration.Conclusion: We present an approach that combines publicly available subcutaneous adipose tissue gene expression datasets with a deconvolution algorithm to calculate subcutaneous adipose tissue cell-type composition. The results showed the expected increased inflammation gene expression profile accompanied by decreased gene expression in pathways related to lipid metabolism and mitochondrial respiration in subcutaneous adipose tissue in individuals characterized by high macrophage frequencies. This approach demonstrates the hidden strength of reusing publicly available data to gain cell-type-specific insights into adipose tissue function.

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