References:Chronic mirabegron treatment increases human brown fat, HDL cholesterol, and insulin sensitivity. Rev. The role and mechanism of action of menthol in topical analgesic products. (2009). This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). [Epub ahead of print]. Cell 150, 620632. Disord. 124, 672683. Biochem. Nutr. Phytother. Dispos. The authors demonstrated a significant increase of EE (by 15.2 kJ/h) in subjects with active BAT. Ther. doi: 10.1016/j.bbrc.2015.09.018, Wang, S., Liang, X., Yang, Q., Fu, X., Zhu, M., Rodgers, B. D., et al. Long-term administration of menthol in mice has been shown to enhance UCP1 expression and activity in BAT, increase EE, ameliorate insulin sensitivity and prevent HFD-induced weight gain. In this report, the authors suggested a potential contribution of SIRT1-mediated deacytelation of PGC-1 in BAT activation (Lagouge et al., 2006; Cant and Auwerx, 2009). (2017). PGC-1alpha, SIRT1 and AMPK, an energy sensing network that controls energy expenditure. 31, Rm. Rev. The administration of resveratrol (400 mg/kg/day for 10 weeks) in mice fed with HFD has shown to reduce visceral fat-pad weights and suppress adipogenesis in epididymal white adipocytes (Kim et al., 2011). (2000). Surg. Res. In a small study, a drug approved to treat overactive bladder boosted brown fat activity and improved glucose metabolism in healthy women. Eicosapentaenoic acid regulates brown adipose tissue metabolism in high-fat-fed mice and in clonal brown adipocytes. (2012). 4, 8896. (2018) demonstrated that administration of low doses of curcumin formulations but having higher bioavailability compared to native curcumin, enhanced in vivo WAT-browning and increased EE in mice. (c) Activation TRPV1 receptors in GIT, and consequent stimulation of the vagal afferent pathways leads to activation of neurons within the ventromedial hypothalamus. Capsaicin induces browning of white adipose tissue and counters obesity by activating TRPV1 channel-dependent mechanisms. In white adipocytes, SIRT1 also induces deacetylation and interaction of PPAR and PR-domanin containing 16 (PRDM16) and thereby regulates key factors involved in BAT development (Qiang et al., 2012). This compound was first found in the roots of white hellebore, and then in mulberries, red wine, grapes and peanuts (Burns et al., 2002). Mol. J. Clin. (2018). Today, the induction of BAT thermogenesis represents a promising protective strategy to combat obesity in humans by increasing EE (Rosenwald and Wolfrum, 2014). Res. Int. Food. The participants took 100 mg of mirabegron every daytwice the FDA-approved dosefor four weeks. doi: 10.1038/nature07221, Virtanen, K. A., Lidell, M. E., Orava, J., Heglind, M., Westergren, R., Niemi, T., et al. 65, 14101423. Pharm. Effects of curcumin consumption on human chronic diseases: a narrative review of the most recent clinical data. (2014). (2007). The thermogenic and anti-obesity effects of capsaicin and capsinoids have been shown to be mediated, at least in part, by the promotion of BAT activity. J. Clin. Wang et al. Food Res. (2016) showed that capsaicin triggered browning of WAT by promoting the expression of SIRT1, UCP1, BMP8B, and PPAR, PGC-1 in white adipocytes. Trp-p8, a novel prostate-specific gene, is up-regulated in prostate cancer and other malignancies and shares high homology with transient receptor potential calcium channel proteins. doi: 10.1111/j.1753-4887.2007.tb00314.x, Bautista, D. M., Siemens, J., Glazer, J. M., Tsuruda, P. R., Basbaum, A. I., Stucky, C. L., et al. Figure 3. The intragastric administration of capsaicin analog in rats induced an increase in SNA of BAT via activation of TRPV1 channels expressed along the gastrointestinal tract (Ono et al., 2011). Dietary menthol-induced TRPM8 activation enhances WAT browning and ameliorates diet-induced obesity. Biotechnol. J. Nutr. (2017) have shown that oral administration by gavage of green tea for 8 weeks improved obesity-related parameters and upregulated the expression of BAT markers (i.e., PPAR-, PRDM-16, and PGC-1) in WAT of rats fed with a HFD-diet. doi: 10.1016/j.pcad.2015.04.003, McKemy, D. D., Neuhausser, W. M., and Julius, D. (2002). Recent studies have demonstrated TRPM8 expression on the membrane of brown and white adipocytes (Ma et al., 2012; Rossato et al., 2014; Jiang et al., 2017). The editor and reviewer's affiliations are the latest provided on their Loop research profiles and may not reflect their situation at the time of review. Res. Epidemiology of obesity and associated comorbidities. It has been shown that fish oil increases the expression of numerous thermogenic genes in BAT including 3 ADRB3, PRDM16, PGC1 and PPARs in BAT (Bargut et al., 2016; Pahlavani et al., 2017). Mechanisms and effects of green tea on cardiovascular health. Our next studies will help determine if mirabegron has metabolic benefits in a wider range of people, including older adults and people with obesity, and if similar drugs might produce these benefits without increasing cardiovascular risk.. Adipose tissue browning and metabolic health. Mol. (2016). Tseng, Y. H., Kokkotou, E., Schulz, T. J., Huang, T. L., Winnay, J. N., Taniguchi, C. M., et al. Mol. Nutr. Am. Then future studies should test the hypothesis whether combined supplementations may also operate synergistically to activate NST in human through activation of BAT and/or beige adipose tissue recruitment. J. Agric. Sci. 22, 13671371. doi: 10.1016/j.cell.2006.11.013, Laiglesia, L. M., Lorente-Cebrin, S., Prieto-Hontoria, P. L., Fernndez-Galilea, M., Ribeiro, S. M., Sinz, N., et al. Front. Biotechnol. J. Agric. Obesity is the consequence of chronic positive energy balance and considered a leading risk factor for cardiovascular and metabolic diseases. These effects were induced via norepinephrine production by alternatively activated macrophages in WAT (Nishikawa et al., 2018). The recent discovery of metabolically active BAT in adult humans has raised the expectations for the development of novel anti-obesity treatments that can regulate brown or beige fat development. Within this study, curcumin treatment was associated with increased UCP1 expression in BAT, possibly involving PPAR-dependent and independent mechanisms (Song et al., 2018). doi: 10.1016/j.mce.2013.12.005, Snitker, S., Fujishima, Y., Shen, H., Ott, S., Pi-Sunyer, X., Furuhata, Y., et al. (2012). doi: 10.1016/j.jnutbio.2007.11.005, Ohyama, K., Nogusa, Y., Shinoda, K., Suzuki, K., Bannai, M., and Kajimura, S. (2016). Relat. (2015a). JAMA 315, 24242434. For centuries, menthol has found application in medical field due to its promising biological properties including antitussive, anti-inflammatory, antipruritic, antibacterial and analgesic effects (Patel et al., 2007). The observed heart changes returned to normal two weeks after treatment stopped. 61:1347480. doi: 10.1080/16546628.2017.1347480, Crescenzo, R., Mazzoli, A., Cancelliere, R., Bianco, F., Giacco, A., Liverini, G., et al. (2015) added evidence that fish oil supplementation in rats for 10 weeks induced a recruitment of beige adipocytes by increasing the expression of UCP1, PGC1, CIDEA and PRDM16 in inguinal WAT. (2018). doi: 10.1111/jcpt.12679, Price, N. L., Gomes, A. P., Ling, A. J., Duarte, F. V., Martin-Montalvo, A., North, B. J., et al. J. Nutr. J. Obes. doi: 10.1016/j.jnutbio.2010.06.006, Rayalam, S., Yang, J. Y., Ambati, S., Della-Fera, M. A., and Baile, C. A. The human body contains more than one type of fat. Prod. Preliminary study. TRPM8, transient receptor potential cation channel melastatin 8; UCP1, uncoupling protein 1; TRPV1, transient receptor potential vanilloid 1; SNA, sympathetic nerve activity; AMPK, adenosine monophosphate-activated protein kinase, SIRT1, sirtuin-1; PGC-1, peroxisome proliferator-activated receptor gamma coactivator 1-alpha; COMT, catechol-O-methyl-transferase cAMP; cyclic adenosine monophosphate; PDEs, phosphodiesterases; PUFAs, polyunsaturated fatty acids; Ac, acetyl group; cAMP, cyclic adenosine monophosphate; EE, energy expenditure; PPAR/ peroxisome proliferator-activated receptor alpha/gamma; PKA, protein kinase A, PRDM16; PR-domain containing 16, (+), stimulation; (), inhibition; , increase. This mechanism of action induces a cold-independent adrenergic response that mediates brown adipogenesis. (2012). 383, 137146. Non-pungent capsaicin analogs (capsinoids) increase metabolic rate and enhance thermogenesis via gastrointestinal TRPV1 in mice. doi: 10.1016/j.physbeh.2006.01.027, Yoneshiro, T., Aita, S., Kawai, Y., Iwanaga, T., and Saito, M. (2012). doi: 10.1007/s00394-014-0655-6, Bargut, T. C., Silva-e-Silva, A. C., Souza-Mello, V., Mandarim-de-Lacerda, C. A., and Aguila, M. B. Results appeared on January 21, 2020, in the Journal of Clinical Investigation. 84, 175184. To this regard, it has been reported that resveratrol can directly inhibit cyclic AMP (cAMP)-specific PDEs in skeletal muscle and WAT of mice leading to elevated intracellular cAMP levels. Effects of novel capsinoid treatment on fatness and energy metabolism in humans: possible pharmacogenetic implications. 20, 98105. 24, 252258. Res. The supplementation of fish oil had shown to increase UCP1 expression (Takahashi and Ide, 2000) and protein levels in interscapular BAT of rats (Kawada et al., 1998). (1999) demonstrated that green tea enhances EE and fat oxidation. Senses 37, 103121. In addition to the well known WAT storing lipids and undergoing pathological structural and functional changes during obesity, mammals including adult humans are also equipped with BAT conferred with thermogenic capacity called adaptive or NST (Virtanen et al., 2009; Rosenwald and Wolfrum, 2014). Res. doi: 10.1016/j.jnutbio.2016.07.019, Lejeune, M. P., Kovacs, E. M., and Westerterp-Plantenga, M. S. (2003). Rev. J. Appl. However, the role of green tea in tackling obesity seemed controversial in several human trials (Huang et al., 2014). doi: 10.1021/jf073420h. doi: 10.1038/ijo.2015.23, Wang, S., Wang, X., Ye, Z., Xu, C., Zhang, M., Ruan, B., et al. Identification of a cold receptor reveals a general role for TRP channels in thermosensation. Biochem. doi: 10.1111/obr.12409, PubMed Abstract | CrossRef Full Text | Google Scholar, Anderson, B. M., and Ma, D. W. (2009). 10, 2436. No use, distribution or reproduction is permitted which does not comply with these terms. Nature 448, 204208. This mechanism of action induces a cold-independent adrenergic response in WAT, leading to an increase in PRDM16 levels and stability. Di Pierro, F., Bressan, A., Ranaldi, D., Rapacioli, G., Giacomelli, L., and Bertuccioli, A. This alkaloid is responsible for the pungency and hotness sensation of chili peppers (Thiele et al., 2008). It has been hypothesized that resveratrol can exert a direct stimulatory effect on SIRT1 (Price et al., 2012), whereas other data indicate an indirect activation via AMP (Wang et al., 2015a). Resveratrol enhances brown adipocyte formation and function by activating AMP-activated protein kinase (AMPK) 1 in mice fed high-fat diet. In a recent report, a combination of mild cold exposure and capsinoids in C57BL/6 mice has been shown to promote the development of both brown and beige adipocytes in inguinal WAT suggesting a centrally mediated effect of capsinoids. Efficacy of a green tea extract rich in catechin polyphenols and caffeine in increasing 24-h energy expenditure and fat oxidation in humans. SIRT1 is a NAD+- dependent deacetylase of several transcription factors including PGC-1, hence modulating oxidative mitochondrial metabolism (Cant and Auwerx, 2009). Moreover, Lejeune et al. Resveratrol exerts anti-obesity effects via mechanisms involving down-regulation of adipogenic and inflammatory processes in mice. Eur. Green tea extract induces genes related to browning of white adipose tissue and limits weight-gain in high energy diet-fed rat. Similarly, Jiang et al. (2009). The authors suggested that fish oil contributes to brown adipogenesis by acting as ligand of TRPV1 in digestive tract that triggers, via the brain, a 2-adrenergical sympathetic response in adipose depots. doi: 10.1093/chemse/bjr100, Ma, S., Yu, H., Zhao, Z., Luo, Z., Chen, J., Ni, Y., et al. Research over the last decades has provided evidence to support the role of bioactive dietary components in the prevention and/or treatment of obesity and associated metabolic disorders (Martnez-Gonzlez et al., 2015; Amiot et al., 2016). Curcumin induces brown fat-like phenotype in 3T3-L1 and primary white adipocytes. J. Clin. More recently, browning of white adipose tissue (WAT) has gained increasing attention in research area as an alternative method in stimulating energy dissipation. Metabolic effects of spices, teas, and caffeine. doi: 10.1038/nrendo.2013.204, Baskaran, P., Krishnan, V., Ren, J., and Thyagarajan, B. doi: 10.1016/j.bcp.2011.03.012, Kobata, K., Sutoh, K., Todo, T., Yazawa, S., Iwai, K., and Watanabe, T. (1999). Omega-3 PUFAs such as DHA and EPA are major polyunsaturated fats found fish oil supplements and in fatty fish such as salmon (Anderson and Ma, 2009). In addition, most studies aimed to assess the impact of green tea catechins on fat oxidation rather than thermogenesis (Rains et al., 2011), therefore more studies are warranted to elucidate the role of green tea in the activation and recruitment of BAT in humans.