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A 28, 919924. (2018). More recently, browning of white adipose tissue (WAT) has gained increasing attention in research area as an alternative method in stimulating energy dissipation. 27, 193202. Menthol: a refreshing look at this ancient compound. (2005). Non-pungent capsaicin analogs (capsinoids) increase metabolic rate and enhance thermogenesis via gastrointestinal TRPV1 in mice. Am. Biotransformation of curcumin through reduction and glucuronidation in mice. doi: 10.1093/ajcn/70.6.1040, Dulloo, A. G., Seydoux, J., Girardier, L., Chantre, P., and Vandermander, J. Within this study, curcumin treatment was associated with increased UCP1 expression in BAT, possibly involving PPAR-dependent and independent mechanisms (Song et al., 2018). 
(2017). This mechanism of action induces a cold-independent adrenergic response that mediates brown adipogenesis. Therefore, the two -adrenergic pathways mediate synergically the capsinoids-induced beige adipocyte biogenesis (Ohyama et al., 2016). doi: 10.1038/nature07221, Virtanen, K. A., Lidell, M. E., Orava, J., Heglind, M., Westergren, R., Niemi, T., et al. Epidemiology of obesity and associated comorbidities. Cell 150, 620632. (2000). 
Jiang, C., Zhai, M., Yan, D., Li, D., Li, C., Zhang, Y., et al. Polyunsaturated fatty acids stimulate de novo lipogenesis and improve glucose homeostasis during refeeding with high fat diet. The current minireview aims to summarize the latest findings concerning the activation of BAT or browning of WAT induced by specific dietary components, including capsaicin, resveratrol, curcumin, green tea, menthol and fish-derived Omega-3 fatty acids. 2, 237257. Biotechnol. (2016). 81, 13431351. Eicosapentaenoic acid promotes mitochondrial biogenesis and beige-like features in subcutaneous adipocytes from overweight subjects. Intragastric administration of capsiate, a transient receptor potential channel agonist, triggers thermogenic sympathetic responses. 4, 8896. BAT is a metabolically active tissue rich in mitochondria containing UCP1 that mediates the uncoupling of electron transport which leads to a decrease in the generation of ATP from adenosine diphosphate (ADP) with subsequent heat production (Bartelt and Heeren, 2014; Rossato et al., 2014). (2004). Enhanced energy expenditure and fat oxidation in humans with high BMI scores by the ingestion of novel and non-pungent capsaicin analogues (capsinoids). Eur. Potential role of bioavailable curcumin in weight loss and omental adipose tissue decrease: preliminary data of a randomized, controlled trial in overweight people with metabolic syndrome. doi: 10.3945/ajcn.2008.26561, Song, Z., Revelo, X., Shao, W., Tian, L., Zeng, K., Lei, H., et al. (2006). 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). Functional brown adipose tissue in healthy adults. J. Nutr. Effects of dietary polyphenols on metabolic syndrome features in humans: a systematic review. doi: 10.1016/j.jnutbio.2016.07.019, Lejeune, M. P., Kovacs, E. M., and Westerterp-Plantenga, M. S. (2003). Figure 1. 61:1600746. doi: 10.1002/mnfr.201600746, Westerterp-Plantenga, M., Diepvens, K., Joosen, A. M., Brub-Parent, S., and Tremblay, A. (2012). doi: 10.1038/nrendo.2013.204, Baskaran, P., Krishnan, V., Ren, J., and Thyagarajan, B. 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). Biochem. Interestingly, green tea extracts have substantial amounts of caffeine which is known for its thermogenic properties (Westerterp-Plantenga et al., 2006).
This project has received funding from the European Unions Horizon 2020 research and innovation program under the Marie Skodowska-Curie Grant Agreement No. doi: 10.4161/adip.26232, Rossato, M., Granzotto, M., Macchi, V., Porzionato, A., Petrelli, L., Calcagno, A., et al. Disord. Food Chem. Food Chem. Drug Metab. This compound was first found in the roots of white hellebore, and then in mulberries, red wine, grapes and peanuts (Burns et al., 2002). doi: 10.1152/japplphysiol.00770.2017, Wang, S., Liang, X., Yang, Q., Fu, X., Rogers, C. J., Zhu, M., et al. A common feature in these animal and human studies was the administration of high doses of curcumin. Similar findings were observed in stromal primary vascular cells separated from interscapular BAT after treatment by resveratrol in vitro (Wang et al., 2017). A synergistic antiobesity effect by a combination of capsinoids and cold temperature through promoting beige adipocyte biogenesis. J. Obes. 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). Cell 3, 421433. doi: 10.1016/j.bbrc.2015.09.018, Wang, S., Liang, X., Yang, Q., Fu, X., Zhu, M., Rodgers, B. D., et al. In a new study, researchers led by Dr. Aaron Cypess from NIHs National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) examined whether a drug called mirabegron could increase brown fat activity in healthy women. (2016). (2016) added evidence on the effect of dietary curcumin (1020 M/day) in inducing a beige phenotype in white adipocytes from rats. Resveratrol improves mitochondrial function and protects against metabolic disease by activating SIRT1 and PGC-1alpha. 19, 840847. (2009). The present study brings scientists closer to identifying a safe, effective way to activate brown fat and potentially treat metabolic disease, Cypess says. Chem. 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. 43, 313319. Summary of the mechanisms involved in the stimulation of brown adipogenesis, mitochondrial biogenesis and energy expenditure by some dietary molecules. 172, 11751178. Opin. Cell Metab. Curcumin, also called diferuloylmethane, is a yellow-colored hydrophobic polyphenol found in extracts of Turmeric roots (a plant of the ginger family). J. B., Freitas, K. M., Lopes, M. T., Guimares, A. L., et al. 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). This alkaloid is responsible for the pungency and hotness sensation of chili peppers (Thiele et al., 2008). Office of Communications and Public Liaison. doi: 10.1016/j.pcad.2015.04.003, McKemy, D. D., Neuhausser, W. M., and Julius, D. (2002). 110, 789798. (b) TRPM8 activation in brown adipocytes enhances the expression of thermogenic genes via Ca2+-dependent PKA signaling pathway. Biophys. Wang et al. The participants took 100 mg of mirabegron every daytwice the FDA-approved dosefor four weeks. 65, 361375. Res. 89, 4550. 19, 41954202. These effects have shown to be mediated by TRPM8 activation in brown adipocytes with consequent Ca2+-dependent PKA phosphorylation (Ma et al., 2012). doi: 10.1001/jama.2016.7602, Kiefer, F. W. (2017). Effects of curcumin consumption on human chronic diseases: a narrative review of the most recent clinical data. Dis. White fat stores extra energy. doi: 10.1021/jf0112973, Cant, C., and Auwerx, J. Takahashi, Y., and Ide, T. (2000). Biosci. doi: 10.1016/j.physbeh.2006.01.027, Yoneshiro, T., Aita, S., Kawai, Y., Iwanaga, T., and Saito, M. (2012). Front. 58, 5060. 5B52, MSC 2094 Endocrinol. The origin and definition of brite versus white and classical brown adipocytes. Too much white fat, a characteristic of obesity, increases the risk of type 2 diabetes, high blood pressure, and other diseases. doi: 10.1021/jf9711000, Khera, R., Murad, M. H., Chandar, A. K., Dulai, P. S., Wang, Z., Prokop, L. J., et al. (2014). Commun. The drug binds to a protein on the surface of cells thats thought to also stimulate brown fat and improve the ability of white fat to break down and release its stored fat into the bloodstream. Am. 95, 845850. Their insulin sensitivity increased by an average of 36%, indicating a reduced risk of diabetes. N. Engl. Green tea is a widely consumed beverage extracted from leaves of Camellia Sinensis. However, despite promising data from murine studies, little is known about the thermogenic activity of n-3 PUFAs in humans. J. Physiol.
Nonpungent capsaicin analogs (capsinoids) increase energy expenditure through the activation of brown adipose tissue in humans. The significance of beige and brown fat in humans. J. Clin. Obesity is the consequence of chronic positive energy balance and considered a leading risk factor for cardiovascular and metabolic diseases. 37, 7682. 124, 672683. The researchers also measured the women'smetabolism, cholesterol and other markers of heart health, and blood sugar and insulin sensitivity (the ability to use insulin properly and control blood sugar levels). Relat. 691061. These beneficial effects are, at least in part, attributable to tea catechins such as EGCG which is the most active catechin in green tea, epigallocatechin, and epicatechin gallate (Basu and Lucas, 2007). PMID: 31961826. Yoneshiro et al. doi: 10.1152/japplphysiol.00128.2010, Pahlavani, M., Razafimanjato, F., Ramalingam, L., Kalupahana, N. S., Moussa, H., Scoggin, S., et al. J. Laparoendosc. Connect. (2014). 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. In C57BL/6J mice, the ingestion of HFD supplemented with resveratrol for 15 weeks led to an increase in adaptive thermogenesis in response to external cooling. The adrenergic stimulation in brown adipocytes can be also promoted by the reduction of degradation of (d) cAMP and (e) norepinephrine through direct inhibition of PDEs and COMT activity, respectively. The participants experienced increases in resting heart rate, blood pressure, and oxygen consumption by the heart while taking the drug. National Institutes of Health, 9000 Rockville Pike, Bethesda, Maryland 20892, U.S. Department of Health and Human Services. A less common type of fat, called brown fat, breaks down blood sugar and fat molecules to create heat and help maintain body temperature. Front. Integr. Resveratrol ameliorates aging-related metabolic phenotypes by inhibiting cAMP phosphodiesterases. Nutr. Moreover, BAT of resveratol-treated mice showed larger mitochondria structures and DNA content, significant increase in gene expression of pathways characteristically related to energy homeostasis, including PPAR involved -oxidation of fatty acids and UCP1. 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. Figure 3.
J. Appl. NIH Research Matters (2009). Characterization of metabolites of the chemopreventive agent curcumin in human and rat hepatocytes and in the rat in vivo, and evaluation of their ability to inhibit phorbol ester-induced prostaglandin E2 production. 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. Nutr. 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. doi: 10.1079/BJN2003938, Lone, J., Choi, J. H., Kim, S. W., and Yun, J. W. (2016). J. Nutr. They are active ingredients found in the non-pungent type of red chili (Kobata et al., 1999). In this review we focused on few dietary molecules that have shown to regulate BAT activation or beige fat development. Technol. HE wrote the manuscript. Brown fat activity, as measured by PET/CT, also increased during the study. doi: 10.1016/j.cell.2012.01.017, Patel, T., Ishiuji, Y., and Yosipovitch, G. (2007). Rev. J. Nutr. 17, 573586. doi: 10.1271/bbb.90555, Kawada, T., Kayahashi, S., Hida, Y., Koga, K., Nadachi, Y., and Fushiki, T. (1998). Cell 15, 11091122. (2016). Menthol is also known to induce cooling sensation by activating the TRPM8 receptor, a Ca2+-permeable non-selective channel that detects cold stimuli in the thermosensory system (McKemy et al., 2002; Bautista et al., 2007). In a recent study, mice fed with HFD in association with curcumin showed an increase in EE and adaptive thermogenesis following mild cold exposure. In this study, the administration of equivalent amounts of caffeine found in green tea extracts failed to induce similar metabolic effects (Dulloo et al., 1999). Rep. 5:18013. doi: 10.1038/srep18013, Kim, S., Jin, Y., Choi, Y., and Park, T. (2011). It was hypothesized that these findings might be influenced by the body composition, dietary habits and ethnicity of the studied populations (Huang et al., 2014). Biochem. These changes were accompanied by increased gene expression of brown fat markers such as FGF21, Tbx1, TMEM26, and CIDEA and some brown cell marker proteins including PRDM16, UCP1 and PGC-1 in a dose-dependent manner. (2008). The role and mechanism of action of menthol in topical analgesic products. It was suggested that green tea catechins may promote the SNA by reducing the degradation of norepinephrine through a direct inhibition of COMT. Moreover, topical application of menthol on skin has been shown to activate TRPM8 and induce parallel increase in NST and body temperature (Tajino et al., 2007; Vizin et al., 2018). The authors demonstrated a significant increase of EE (by 15.2 kJ/h) in subjects with active BAT. Similarly, AMPK can also directly enhance PGC1 activity by phosphorylation, thus increasing mitochondrial biogenesis.