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(1999). The observed heart changes returned to normal two weeks after treatment stopped. (2017). Chem. Food. J. Agric. (2016) showed that capsaicin triggered browning of WAT by promoting the expression of SIRT1, UCP1, BMP8B, and PPAR, PGC-1 in white adipocytes.

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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. 32, 957975. Br. Rep. 5:18013. doi: 10.1038/srep18013, Kim, S., Jin, Y., Choi, Y., and Park, T. (2011). 65, 361375. (2015b). Amiot, M. J., Riva, C., and Vinet, A. The synergistic thermogenic effect exerted by EGCG and caffeine was further confirmed after administration of encapsulated EGCG-caffeine mixtures (Brub-Parent et al., 2005). (2014). doi: 10.1152/ajpregu.00377.2007. Dispos.

(2008). (1999) demonstrated that green tea enhances EE and fat oxidation. Dietary curcumin intervention targets mouse white adipose tissue inflammation and brown adipose tissue UCP1 expression. doi: 10.1038/nature719, Nishikawa, S., Kamiya, M., Aoyama, H., Nomura, M., Hyodo, T., Ozeki, A., et al. Resveratrol increases brown adipose tissue thermogenesis markers by increasing SIRT1 and energy expenditure and decreasing fat accumulation in adipose tissue of mice fed a standard diet. doi: 10.4161/adip.26232, Rossato, M., Granzotto, M., Macchi, V., Porzionato, A., Petrelli, L., Calcagno, A., et al. 2, 237257. J. Appl. This project has received funding from the European Unions Horizon 2020 research and innovation program under the Marie Skodowska-Curie Grant Agreement No. The participants experienced increases in resting heart rate, blood pressure, and oxygen consumption by the heart while taking the drug. (2017). This effect was inhibited by an extrinsic denervation of the jejunal segment suggesting a role of the gastrointestinal vagus nerve in capsinoids-mediated thermogenesis (Kawabata et al., 2009). Res. Surg. 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). Sci. In this study, curcumin administration increased weight loss, enhanced the fat mass loss and induced a reduction in waist and hip circumference (Di Pierro et al., 2015). 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. The PPAR/PRDM16 complex is also able to bind and activate PGC1, another cofactor specifically expressed in brown and beige adipocytes that stimulates the transcription of several genes involved in thermogenesis and mitochondrial biogenesis. Effects of curcumin consumption on human chronic diseases: a narrative review of the most recent clinical data. Interestingly, green tea extracts have substantial amounts of caffeine which is known for its thermogenic properties (Westerterp-Plantenga et al., 2006). Mechanisms and effects of green tea on cardiovascular health.

Recently, dietary n-3 PUFAs has shown to lower the amount of visceral WAT and increase the mass of interscapular BAT in rats (Crescenzo et al., 2017). This mechanism of action induces a cold-independent adrenergic response that mediates brown adipogenesis. J. Nutr. 383, 137146. 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). 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. Wang et al. Nutr. Mol. Adipocyte 3, 49. In a recent study, mice fed with HFD in association with curcumin showed an increase in EE and adaptive thermogenesis following mild cold exposure. thermogenesis controlling fgf9 mediated fgf6 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. Taken together, these results suggest that resveratrol plays a crucial role in brown adipocytes formation and activation by enhancing the AMPKSIRT1PGC-1 signaling pathway. Fish (Bonito) oil supplementation enhances the expression of uncoupling protein in brown adipose tissue of rat. In this review we focused on few dietary molecules that have shown to regulate BAT activation or beige fat development. J. Rev. Pan, M. H., Huang, T. M., and Lin, J. K. (1999). Green tea and thermogenesis: interactions between catechin-polyphenols, caffeine and sympathetic activity. Resveratrol improves mitochondrial function and protects against metabolic disease by activating SIRT1 and PGC-1alpha. adipose tissue triglyceride impaired hyperlipidemia corrects key tomography Pharmacol. Nutr.

Physiol. The origin and definition of brite versus white and classical brown adipocytes. In another randomized placebo-controlled study, capsinoids (10 mg/kg per day) were able to increase EE, VO2, and enhance fat burning (Inoue et al., 2007). On the other hand, only a slight increase in EE (by 1.7 kJ/h) after oral administration of capsinoids was observed in the BAT-negative group (Yoneshiro et al., 2012). Yoneshiro et al. (2007). Biochem. Moreover, current knowledge deriving from cell culture and animal models suggests that polyphenols, mainly curcumin, and resveratrol, exert their thermogenic effect when supplemented at doses that are quite elevated. Resveratrol induces brown-like adipocyte formation in white fat through activation of AMP-activated protein kinase (AMPK) 1. Nutr. Chen et al. MR proofread the manuscript and provided guidance on the overall direction of the manuscript. Br. Senses 37, 103121. More recently, browning of white adipose tissue (WAT) has gained increasing attention in research area as an alternative method in stimulating energy dissipation. 95, 845850. Effects of novel capsinoid treatment on fatness and energy metabolism in humans: possible pharmacogenetic implications. fat brown activating activate stress nottingham beauty feb range Bldg. doi: 10.1038/nature07221, Virtanen, K. A., Lidell, M. E., Orava, J., Heglind, M., Westergren, R., Niemi, T., et al. Physiol. Dis. J. Nutr. The significance of beige and brown fat in humans. 70, 10401045. Benefits of the mediterranean diet: insights from the PREDIMED study. Effects of encapsulated green tea and guarana extracts containing a mixture of epigallocatechin-3-gallate and caffeine on 24 h energy expenditure and fat oxidation in men. doi: 10.1056/NEJMoa0808949, Vizin, R. C. L., Motzko-Soares, A. C. P., Armentano, G. M., Ishikawa, D. T., Cruz-Neto, A. P., Carrettiero, D. C., et al.

Res. brown adipocytes adipocyte activation researchers reveal element key related Tea catechins enhance the mRNA expression of uncoupling protein 1 in rat brown adipose tissue. fat cells brown under microscope identify activating lynchpin researchers sciguru shown In addition, in inguinal WAT fish oil exerts its browning effects by recruiting beige adipocytes. doi: 10.1016/j.jnutbio.2015.09.006, Ludy, M. J., Moore, G. E., and Mattes, R. D. (2012). J. Nutr. Taken together, these findings reinforce evidence about the prospective use of menthol as a promising approach in the management of obesity and associated comorbidities by regulating energy balance and metabolic homeostasis. (2009). J. Clin.

Med. Brown fat activity, as measured by PET/CT, also increased during the study. This alkaloid is responsible for the pungency and hotness sensation of chili peppers (Thiele et al., 2008). Brown remodeling of white adipose tissue by SirT1-dependent deacetylation of Ppar. Curcumin, also called diferuloylmethane, is a yellow-colored hydrophobic polyphenol found in extracts of Turmeric roots (a plant of the ginger family). Human white adipocytes express the cold receptor TRPM8 which activation induces UCP1 expression, mitochondrial activation and heat production. Biochem. Physiol. J. Clin. Low concentrations of resveratrol have been shown to promote the expression of brown adipogenic markers including UCP1, PRDM16, PGC1 and CIDEA in stromal vascular cells isolated from mouse inguinal WAT, suggesting a main role of resveratrol in WAT browning (Wang et al., 2015a). Chili pepper fruits: presumed precursors of fatty acids characteristic for capsaicinoids. (2015a). Biochem. 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. The role and mechanism of action of menthol in topical analgesic products. Pharmacol. doi: 10.1530/EC-17-0037, Kim, K. H., and Park, Y. Capsaicin (8-methyl-N-vanillyl-6-nonenamide) is an active component of hot pepper and belongs to the capsicum genus of plants.

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). The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. Moreover, Lejeune et al. (2008) provided additional evidence for the inhibitory effects of resveratrol on adipogenesis. 27, 193202. 24, 252258. Cardiovasc. Obesity is defined as an abnormal body fat accumulation due to chronic periods of imbalance between energy intake and expenditure. doi: 10.1038/nature05910, Brub-Parent, S., Pelletier, C., Dor, J., and Tremblay, A. 19, 41954202. (2016). TRPM8 is also expressed in significant amounts in the lungs, male reproductive system and cancerous tissues where its function is yet not well understood (Tsavaler et al., 2001; Stein et al., 2004). Physiol. Antiobesity effects of green tea catechins: a mechanistic review. Nutr. Endocr. 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. Curr. SIRT1 is required for AMPK activation and the beneficial effects of resveratrol on mitochondrial function. 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. 15, 675690. 466, 247253. 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. Within this study, curcumin treatment was associated with increased UCP1 expression in BAT, possibly involving PPAR-dependent and independent mechanisms (Song et al., 2018). Biosci.

J. Appl. Mol. Food Chem. 110, 789798. J. Clin. Nonpungent capsaicin analogs (capsinoids) increase energy expenditure through the activation of brown adipose tissue in humans. 61, 10581064. Commun. J. Nutr. doi: 10.1146/annurev-food-022510-133656, Kim, M., Goto, T., Yu, R., Uchida, K., Tominaga, M., Kano, Y., et al. 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. (2015). Interestingly, menthol administration protected mice against HFD-obesity and enhanced beige adipocytes (Jiang et al., 2017). Activation of brown adipose tissue (BAT) represents today a promising strategy to enhance energy expenditure (EE) through heat production. Office of Communications and Public Liaison. doi: 10.1021/jf0112973, Cant, C., and Auwerx, J. doi: 10.1016/j.jnutbio.2010.06.006, Rayalam, S., Yang, J. Y., Ambati, S., Della-Fera, M. A., and Baile, C. A. (2017). Cancer Res. Jiang, C., Zhai, M., Yan, D., Li, D., Li, C., Zhang, Y., et al. (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. 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. J. Clin. Prod. doi: 10.1016/j.mce.2013.12.005, Snitker, S., Fujishima, Y., Shen, H., Ott, S., Pi-Sunyer, X., Furuhata, Y., et al. 37, 7682. Comp. However, the effect of this resveratrol-mediated by cAMP signaling pathway on brown adipogenesis remains to be elucidated (Park et al., 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. Cypess lab, Journal of Clinical Investigation, U.S. Department of Health & Human Services, NIH Institute and Center Contact Information, Microneedle Patch Shrinks Fat Tissue in Mice, Nanoparticles Target, Transform Fat Tissue, Drug Activates Brown Fat and Increases Metabolism, Cool Temperature Alters Human Fat and Metabolism, Shivering Triggers Brown Fat to Produce Heat and Burn Calories. doi: 10.1016/j.jnutbio.2016.07.019, Lejeune, M. P., Kovacs, E. M., and Westerterp-Plantenga, M. S. (2003). A recent clinical trial assessed the safety and effectiveness of 30 day treatment with curcumin combined with phosphatidylserine in overweight subjects undergoing weight loss by diet and lifestyle intervention. Cell 150, 620632. 8:33. doi: 10.1186/1476-511X-8-33, Andolfi, C., and Fisichella, P. M. (2018).

56, 42194224. adipose thyroid hormones peripheral tissues deiodinase trh neurons Are all n-3 polyunsaturated fatty acids created equal? (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. (2018). Nature 454, 10001004.

58, 5060. However, despite promising data from murine studies, little is known about the thermogenic activity of n-3 PUFAs in humans. Several reports indicated that green tea may induce weight loss by enhancing EE and fat oxidation in humans (Westerterp-Plantenga et al., 2006). Nature 416, 5258. (2001). doi: 10.18632/oncotarget.20540, Kawabata, F., Inoue, N., Masamoto, Y., Matsumura, S., Kimura, W., Kadowaki, M., et al. Di Pierro, F., Bressan, A., Ranaldi, D., Rapacioli, G., Giacomelli, L., and Bertuccioli, A. Tseng, Y. H., Kokkotou, E., Schulz, T. J., Huang, T. L., Winnay, J. N., Taniguchi, C. M., et al. Front. doi: 10.1093/chemse/bjr100, Ma, S., Yu, H., Zhao, Z., Luo, Z., Chen, J., Ni, Y., et al. 89, 4550. (2007). These effects have shown to be mediated by TRPM8 activation in brown adipocytes with consequent Ca2+-dependent PKA phosphorylation (Ma et al., 2012). activate burning fat energy healthy brown federation obesity (2016) have recently shown that EPA induces a switch from white to beige-like adipocytes in human subcutaneous adipocytes of overweight subjects by promoting the activation of AMPK/SIRT1/PGC1- axis. doi: 10.3945/ajcn.111.018606, Keywords: brown adipose tissue, capsaicin, resveratrol, green tea, curcumin, menthol, Omega-3 polyunsaturated fatty acids, Citation: El Hadi H, Di Vincenzo A, Vettor R and Rossato M (2019) Food Ingredients Involved in White-to-Brown Adipose Tissue Conversion and in Calorie Burning. Endocrinol. J. Urol. J. Nat. Obes. O'Mara AE, Johnson JW, Linderman JD, Brychta RJ, McGehee S, Fletcher LA, Fink YA, Kapuria D, Cassimatis TM, Kelsey N, Cero C, Abdul-Sater Z, Piccinini F, Baskin AS, Leitner BP, Cai H, Millo CM, Dieckmann W, Walter M, Javitt NB, Rotman Y, Walter PJ, Ader M, Bergman RN, Herscovitch P, Chen KY, Cypess AM. (2008). Resveratrol reduced adipocytes viability and downregulated the expression of adipogenic factors such as SREBP-1c, LPL, C/EBP-, HSL, and PPAR. Furthermore, Laiglesia et al. Biotechnol. Cell 15, 11091122. doi: 10.1016/j.bcp.2011.03.012, Kobata, K., Sutoh, K., Todo, T., Yazawa, S., Iwai, K., and Watanabe, T. (1999). Am.

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. On the other hand, approaches aimed to enhance EE represent an alternative tool for counteracting obesity and related cardiometabolic disorders (Khera et al., 2016). doi: 10.1152/japplphysiol.00770.2017, Wang, S., Liang, X., Yang, Q., Fu, X., Rogers, C. J., Zhu, M., et al. Integr. Biotransformation of curcumin through reduction and glucuronidation in mice. 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). Dulloo, A. G., Duret, C., Rohrer, D., Girardier, L., Mensi, N., Fathi, M., et al.

50, 33373340. Curcumin induces brown fat-like phenotype in 3T3-L1 and primary white adipocytes. (2009). The oral treatment with capsinoids (6 mg/kg for 12 weeks) in overweight or obese subjects was associated with abdominal fat loss and increase in fat oxidation compared with placebo group (Snitker et al., 2009). Long exposure to cold temperatures has been shown to boost brown fat activity but may not be a practical approach for most people. 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.. Ireson, C., Orr, S., Jones, D. J., Verschoyle, R., Lim, C. K., Luo, J. L., et al. Eicosapentaenoic acid regulates brown adipose tissue metabolism in high-fat-fed mice and in clonal brown adipocytes. These findings were supported by another study that showed a TRPV1-dependent increase in the temperature of the colon and intrascapular BAT after jejunal administration of capsinoids in mice. Res. Res. brown participants adipose metabolic tissue role health 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). Application of menthol to the skin of whole trunk in mice induces autonomic and behavioral heat-gain responses. 61:1600746. doi: 10.1002/mnfr.201600746, Westerterp-Plantenga, M., Diepvens, K., Joosen, A. M., Brub-Parent, S., and Tremblay, A. Nat. sunrider activation metabolism adipose 39, 967976.

Pharm. 22, 13671371. 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).

(2015). Eur. A major concern is the high risk of accompanying cluster of comorbidities, such as CVDs, metabolic syndrome and some forms of cancer (Andolfi and Fisichella, 2018). doi: 10.1016/j.cell.2012.06.027, Rains, T. M., Agarwal, S., and Maki, K. C. (2011). Biophys. doi: 10.1097/MOL.0b013e328328d0a4, Chen, L. H., Chien, Y. W., Liang, C. T., Chan, C. H., Fan, M. H., and Huang, H. Y. Therefore, the two -adrenergic pathways mediate synergically the capsinoids-induced beige adipocyte biogenesis (Ohyama et al., 2016). Two women reported mild side effects, including heart palpitations. (2011). nerve innervation regulates nerves doi: 10.1038/ejcn.2014.143, Inoue, N., Matsunaga, Y., Satoh, H., and Takahashi, M. (2007).

Rev. 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. The team recruited 14 women, aged 18-40, of diverse ethnicities. doi: 10.1016/j.jnutbio.2007.11.005, Ohyama, K., Nogusa, Y., Shinoda, K., Suzuki, K., Bannai, M., and Kajimura, S. (2016). The authors demonstrated a significant increase of EE (by 15.2 kJ/h) in subjects with active BAT. Rev. Similar findings were observed in stromal primary vascular cells separated from interscapular BAT after treatment by resveratrol in vitro (Wang et al., 2017). Park, S. J., Ahmad, F., Philp, A., Baar, K., Williams, T., Luo, H., et al. J Clin Invest. The effects of capsaicin and capsiate on energy balance: critical review and meta-analyses of studies in humans.

To this regard, Nishikawa et al. doi: 10.1093/ajcn/70.6.1040, Dulloo, A. G., Seydoux, J., Girardier, L., Chantre, P., and Vandermander, J. doi: 10.1038/sj.ijo.0801101, Huang, J., Wang, Y., Xie, Z., Zhou, Y., Zhang, Y., and Wan, X. (2006). doi: 10.1111/bph.13514, Basu, A., and Lucas, E. A. Polyunsaturated fatty acids stimulate de novo lipogenesis and improve glucose homeostasis during refeeding with high fat diet. J. Laparoendosc. ucp1 thermogenesis signaling adipocytes acute Resveratrol induces apoptosis and inhibits adipogenesis in 3T3-L1 adipocytes. The activation of EPAC, a cAMP effector, leads to increased intracellular calcium (Ca2+) concentration that activates AMPK pathway and subsequently increase SIRT1 activity. (2012). (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. Dietary n-3 fatty acids affect mRNA level of brown adipose tissue uncoupling protein 1, and white adipose tissue leptin and glucose transporter 4 in the rat. NIH Research Mattersis a weekly update of NIH research highlights reviewed by NIHs experts. Takahashi, Y., and Ide, T. (2000). 19, 840847. 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). New role of bone morphogenetic protein 7 in brown adipogenesis and energy expenditure. J. Clin. Adipose tissue browning and metabolic health. Res. (2009). Res. doi: 10.1038/nrendo.2013.204, Baskaran, P., Krishnan, V., Ren, J., and Thyagarajan, B. PGC-1alpha, SIRT1 and AMPK, an energy sensing network that controls energy expenditure. Eur. Biochem. These effects were induced via norepinephrine production by alternatively activated macrophages in WAT (Nishikawa et al., 2018). This minireview aims to summarize the current knowledge of some dietary compounds that have been shown to promote BAT activation and WAT browning with subsequent beneficial health effects. 9:1954. doi: 10.3389/fphys.2018.01954. 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. White fat stores extra energy. (b) TRPM8 activation in brown adipocytes enhances the expression of thermogenic genes via Ca2+-dependent PKA signaling pathway. 55, 159169. Similarly, Jiang et al.

A 28, 919924.

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. 46, 12251227. 61:1347480. doi: 10.1080/16546628.2017.1347480, Crescenzo, R., Mazzoli, A., Cancelliere, R., Bianco, F., Giacco, A., Liverini, G., et al. 4, 8896. However, catechins and caffeine may synergically mediate an adrenergic-induced BAT thermogenesis by acting at different check-points of the norepinephrine-cAMP axis.