Skip Navigation
Skip to contents

Diabetes Metab J : Diabetes & Metabolism Journal

Search
OPEN ACCESS

Articles

Page Path
HOME > Diabetes Metab J > Volume 37(1); 2013 > Article
Review
Obesity and Metabolic Syndrome Brown Adipose Tissue as a Regulator of Energy Expenditure and Body Fat in Humans
Masayuki Saito
Diabetes & Metabolism Journal 2013;37(1):22-29.
DOI: https://doi.org/10.4093/dmj.2013.37.1.22
Published online: February 15, 2013
  • 5,917 Views
  • 86 Download
  • 91 Crossref
  • 98 Scopus

Department of Nutrition, Tenshi College, Sapporo, Japan.

Corresponding author: Masayuki Saito. Department of Nutrition, Tenshi College, 31-2, Kita 13, Higashi 3, Higashiku, Sapporo 065-0013, Japan. saito@tenshi.ac.jp

Copyright © 2013 Korean Diabetes Association

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

  • Brown adipose tissue (BAT) is recognized as the major site of sympathetically activated nonshivering thermogenesis during cold exposure and after spontaneous hyperphagia, thereby controling whole-body energy expenditure and body fat. In adult humans, BAT has long been believed to be absent or negligible, but recent studies using fluorodeoxyglucose-positron emission tomography, in combination with computed tomography, demonstrated the existence of metabolically active BAT in healthy adult humans. Human BAT is activated by acute cold exposure, being positively correlated to cold-induced increases in energy expenditure. The metabolic activity of BAT differs among individuals, being lower in older and obese individuals. Thus, BAT is recognized as a regulator of whole-body energy expenditure and body fat in humans as in small rodents, and a hopeful target combating obesity and related disorders. In fact, there are some food ingredients such as capsaicin and capsinoids, which have potential to activate and recruit BAT via activity on the specific receptor, transient receptor potential channels, thereby increasing energy expenditure and decreasing body fat modestly and consistently.
We are now facing a worldwide epidemic of obesity, a major risk factor in the development of common diseases such as diabetes mellitus, dyslipidemias, fatty liver, hypertension, and arteriosclerosis. Obesity is the state of excessive accumulation of triglyceride in adipose tissues because of a prolonged positive energy balance. In mammals, there are two types of adipose tissue, white and brown adipose tissues (BAT). The two tissues are similar in their major population of adipocyte having intracellular lipid droplets, but are quite different in the physiological functions. White adipose tissue (WAT) is the primary site of energy storage, while BAT is specialized for energy expenditure. In small rodents, BAT is recognized as the major site of sympathetically activated nonshivering thermogenesis during cold exposure and after spontaneous hyperphagia, thereby controling whole-body energy expenditure and body fat [1,2]. In adult humans, BAT has long been believed to be absent or negligible, but recent studies using fluorodeoxyglucose (FDG)-positron emission tomography (PET), in combination with computed tomography (CT), demonstrated the existence of metabolically active BAT in adult humans [3]. This review summarizes recent knowledge on human BAT, with special reference to its thermogenic and antiobesity activities.
The structure of adipocytes in WAT is characterized by a single large lipid droplet and a small number of mitochondria, while adipocytes in BAT contain numerous small lipid droplets surrounded by a large number of mitochondria. In BAT mitochondria, there is a unique uncoupling protein 1 (UCP1) in the inner membrane [4]. As UCP1 is expressed selectively in BAT, but not in other tissues including WAT, it is recognized as a specific molecular marker of brown adipocyte. UCP1 acts to uncouple oxidative phosphorylation from ATP synthesis, thereby dissipating energy as heat. BAT thermogenesis is directly regulated by sympathetic nerves distributed abundantly to this tissue (Fig. 1). The cellular events associated with sympathetic activation of BAT thermogenesis are the binding of norepinephrine released from sympathetic nerve terminals to b-adrenergic receptors, the activation of adenylate cyclase and hormone-sensitive lipase, which hydrolyzes intracellular triglyceride. The released fatty acids activate UCP1 and are oxidized in mitochondria to serve as an energy source of thermogenesis.
Thus, the principal substrate for BAT thermogenesis is fatty acids from triglyceride in this tissue and also from circulating free fatty acids and lipoproteins. Sympathetic activation also results in an increased fat mobilization in WAT, and released fatty acids are used in BAT as well as muscle tissues. Together with fatty acids, glucose is also an important fuel in BAT, probably not as a direct substrate for thermogenesis but as a carbon source for fatty acid synthesis and rapid oxidation of fatty acids. Moreover, as UCP1, because of its uncoupling activity, decreases the cellular energy charge, glucose is indispensable for rapid recovery of cellular ATP levels by activation of anaerobic glycolysis [5,6].
Most information about BAT has come from experimental studies in small rodents. In humans, significant amounts of BAT are present in newborns and may contribute to body temperature regulation during the neonatal period, probably in the same way as in small rodents. However, BAT seems to disappear rapidly during postnatal periods and in adults is rather difficult to identify by conventional anatomical and histological examinations [7]. Thus, it has been a general contention that BAT is absent or of minute amounts and plays negligible, if any, roles in adult humans [8,9]. The existence of metabolically active BAT in adult humans has been suggested by the clinical studies using FDG-PET, one of the powerful diagnostic tools for malignant tumors: that is, PET sometimes detects symmetrical FDG uptake in the shoulder and thoracic spine regions, where no tumor is present. By simultaneous examinations with PET and X-ray CT, the site of the FDG uptake was identified as adipose tissue, named as "USA-fat" [10]. Such FDG uptake is increased at lower environmental temperatures [10,11], and reduced by pretreatment with b-adrenergic blockers [12,13]. Animal studies demonstrated that β-adrenergically stimulated 2-deoxyglucose uptake into BAT is totally dependent on the activation of UCP1 [6]. These findings collectively suggest that the FDG uptake in adipose tissue at the specific regions reflects the metabolic activity of BAT.
The presence of BAT in adult humans was confirmed by the experimental FDG-PET/CT studies for healthy volunteers [14-17]. For example, when exposed to cold (19℃) with light clothing for 2 hours, some participants show a substantial FDG uptake into adipose tissue in the supraclavicular and paraspinal regions (Fig. 2), whereas they showed no detectable uptake when kept warm (27℃). Histological examinations revealed the presence of UCP-1 positive brown adipocytes in these regions. Our study for 213 healthy participants aged 20 to 73 years revealed that the prevalence of cold-activated BAT was more than 50% in young subjects of the twenties, decreased with age, and in less than 10% of the fifties and sixties [18]. It is to be noted that BAT can be well identified by FDG-PET/CT only when exposed to acute cold in winter [15]. This may be a reason of the low (<10%) prevalence of BAT in clinical studies [19-23], in which FDG-PET/CT is carried out at warm conditions at around 24℃ with normal clothing.
It has been established in small rodents that BAT is the major site for adaptive nonshievering thermogenesis, a physiological process during which heat production increases in response to environmental changes. One of the typical examples is cold-induced thermogenesis. When mammals are exposed to cold, they maintain body temperature autonomically not only by decreasing heat loss from body surface but also by increasing heat production. At least two mechanisms contribute to cold-induced thermogenesis, shivering of skeletal muscle and activation of BAT. The critical role of BAT for cold-induced thermogenesis was clearly confirmed by a finding that mice lacking UCP1 is unable to maintain body temperature under a cold environment and die in hours [24].
In humans, the fact that the metabolic activity of BAT is increased after cold exposure suggests a contribution of BAT to cold-induced thermogenesis. In fact, we [25] and Orava et al. [26], by measuring whole-body energy expenditure in participants showing detectable cold-activated FDG uptake (BAT-positive group) and also those showing undetectable uptake (BAT-negative group), demonstrated that energy expenditure after acute cold exposure was higher in the BAT-positive than -negative group, while the basal energy expenditure at warm conditions was almost comparable in the two groups. A positive correlation was found between the cold-induced rise in energy expenditure and the BAT activity quantified from FDG uptake [25]. These findings clearly indicate a significant role of BAT for cold-induced thermogenesis in humans. Moreover, we [25] found that the response of the skin temperature to cold exposure was different between the BAT-positive and -negative groups; that is, the cold-induced temperature drop in the skin region close to BAT deposits is smaller in the BAT-positive group, while no significant difference in other skin regions apart from BAT deposits. These results indicate that BAT thermogenesis is actually activated during cold exposure and probably contributes to body temperature regulation.
Another example of adaptive thermogenesis is diet-induced thermogenesis, an increase in energy expenditure seen after food intake, which is sometimes called as "postprandial thermogenesis" or "thermic effect of food." Since the first report of BAT hyperplasia in small rodents kept on prolonged overfeeding on highly palatable cafeteria-diets [27], BAT has been proposed as a site of diet-induced thermogenesis [1]. It is well known that a change in energy intake results in an adaptive change in energy expenditure so that body energy content is kept at steady levels. In support of this, it has repeatedly been reported that BAT mass and/or UCP1 expression are decreased in animals deprived from food but increased in those fed on high fat diets [2]. However, it is to be noted that the effects of chronic hyperphagia may not be equal to the cumulative effects of single ingestions of food. To our knowledge, there has been no report showing direct evidence for the involvement of BAT in diet-induced thermogenesis in small rodents [28]. In humans, however, BAT may contribute, at least in part, to diet-induced thermogenesis, because whole-body energy expenditure increased after an oral ingestion of food more in BAT-positive than -negative participants, particularly during the initial period of 1 hour (Aita et al., unpublished observations).
Thus, it seems likely that human BAT is involved in adaptive thermogenesis, thereby regulating whole-body energy expenditure. This is supported by some previous studies examining the effects of UCP1 gene polymorphism. In the human UCP1 gene, there is a single nucleotide substitution at -3826A to G [29], which lowers UCP1 mRNA expression [30,31], accelerates the age-related reduction of BAT prevalence [18,32], and attenuates cold- and diet-induced thermogenesis [33,34].
Consistent with the significant role of BAT in short-term regulation of energy expenditure, there have been piles of evidence for BAT as a long-term regulator of energy balance and body fat content: that is, for examples, almost all obese model animals express lower levels of UCP1 in BAT, while mice over-expressing UCP1 are leaner, and prolonged cold exposure and/or b3-adrenoceptor agonist treatment result in a reduction of body fat associated with BAT hyperplasia [1,2]. Enerback et al. [24] first reported that mice lacking UCP1 are cold-sensitive but not obese. This paradoxical finding was re-examined by Kontani et al. [35], who demonstrated that these mice get obese when they are kept on a high-fat diet for more than half a year. Feldmann et al. [36] also reported that mice lacking UCP1 are susceptible to diet-induced obesity when they are maintained at thermoneutral temperatures (~29℃), but not at conventional animal room temperatures (18℃ to 22℃). Thus, the preventive effect of UCP1 against obesity is actualized only when animals need not to increase cold-induced thermogenesis, indicating some interactive effects of cold and food on BAT and whole-body energy expenditure.
In humans, both clinical and experimental studies have consistently shown significant inverse relationships between the activity/prevalence of BAT and adiposity-related parameters such as body mass index (BMI), body fat content, and visceral fat accumulation. Retrospective readings of FDG-PET/CT in thousands of patients have revealed that BAT prevalence is lower in patients with higher BMI [19,21,22]. Prospective studies in healthy participants also demonstrated that the prevalence and activity of cold-activated BAT deceased with increasing adiposity [15,16]. The apparent association between BAT prevalence and adiposity, however, is to be carefully evaluated, because these are considerably influenced by age. In fact, the mean age is lower in the BAT-positive participant group than the BAT-negative group. More detailed analysis revealed that the prevalence of cold-activated BAT is more than 50% in young subjects of the twenties, decreased with age, and in less than 10% of the fifties and sixties [18]. A strong impact of age on BAT prevalence has also been reported in various clinical studies [19,21,22]. On the other hand, it is well known that the aging process produces notable changes in body composition: that is, in general, percent body fat increases while lean mass and bone mineral density decreases [37]. Thus, it seems likely that age-related accumulation of body fat is associated with decreased BAT activity (Fig. 3). This is supported by the findings that the adiposity-related parameters increased with age in the BAT-negative group, while they remained unchanged from the twenties to forties in the BAT-positive group [18].
The finding that BAT is protective against body fat accumulation has encouraged the search how to activate or recruit BAT (Fig. 3). This is particularly intriguing because people with lower or undetectable BAT activities are more obese and to be treated. As noted previously, cold seems the most physiological and powerful stimulus for activation of BAT. Mice exposed to cold at 4℃, for example, show a substantial increase in sympathetic nerve activity in BAT, followed by the serial activation of the intracellular events shown in Fig. 1. Furthermore, prolonged cold exposure elicits an increased UCP1 expression, mitochondriogenesis, and proliferation and differentiation of brown adipocyte, all of which result in BAT hyperplasia and an increased thermogenic capacity [1]. Particularly interesting is that chronic sympathetic activation produces not only BAT hyperplasia but also a remarkable induction of UCP1-positive brown-like adipocytes in white fat pads, called as "beige or brite" cells [38-40]. These beige cells belong to a cell lineage different from "classical" brown adipocytes, but also contribute to adaptive thermogenesis and body fat reduction [41-43]. Very recently, Wu et al. [44] identified some genes expressed selectively in mouse beige cells and found their high levels of expression in human supraclavicular fat deposits identified as BAT by FDG-PET/CT. Lee et al. [45] reported that preadipocytes isolated from human supravicular fat were capable of differentiating into UCP1-positive adipocytes in vitro, regardless of FDG-PET status. Moreover, we found that BAT activity in humans is remarkably increased during winter in individuals who showed undetectable activities in summer [22]. All these data suggest that human BAT identified by FDG-PET/CT is largely composed of beige cells and is inducible in response to appropriate sympathetic stimulation. In fact, when our participants with undetectable or low BAT activity were kept in a cold environment at 15℃ to 17℃ for 2 hours every day for 6 weeks, their BAT activity was significantly increased (Yoneshiro et al., unpublished data). More importantly, the change in BAT activity was negatively correlated with those in body fat content. These results indicate that human BAT can be induced and/or recruited, and is involved in reducing body fat.
Although daily cold exposure can recruit human BAT, it would seem difficult to increase exposure to cold in daily life. It is now well established that cold stimulus is received by transient receptor potential channels (TRP) (Fig. 1). Among the members of the TRP family, TRPM8 and TRPA1 are the most likely receptor candidates sensitive to low temperatures [46]. The mean activation temperatures of TRPA1 and TRPM8 are around 20℃, being comparable with those applied in human studies to activate BAT. Accordingly, chemical activation of these receptors would mimic the effects of cold exposure. Actually, there are various ingredients in food acting as agonists for these TRPs [46], a representative of which is menthol, a cooling and flavor compound in mint, acting on TRPM8. TRPA1 is activated by allyl- and benzyl-isothiocyanates, pungent elements in mustard and Wasabi (Japanese horseradish). Among the TRP agonists, the most extensively studied is capsaicin, a pungent principle of chili pepper, which is a potent agonist for TRPV1. There have been many animal studies demonstrating that capsaicin and its nonpungent analogs (capsinoids) increase BAT thermogenesis through the activation of TRPV1 and the sympathetic nervous system, and decrease body fat. Recent human studies have also confirmed similar thermogenic and antiobesity effects of capsinoids [47-49]. Thus, capsaicin/capsinoids as well as other food ingredients activating TRPs are promising as an antiobesity regimen easily applicable in daily life.
In addition to the regulatory roles of BAT in energy expenditure and body fat content, BAT may be relevant to some metabolic disorders. It has repeatedly been reported that cold acclimated animals show improved insulin sensitivity and enhanced glucose utilization in various peripheral tissues including BAT [50-53]. Bartelt et al. [54] visualized the in vivo processing of lipoproteins and demonstrated a regulatory role of BAT in plasma triglyceride metabolism in hyperlipidemia and obesity. Moreover, Nishio et al. [55] reported augmented glucose and lipid tolerance in mice transplanted with functional brown adipocytes developed from human pluripotent stem cells. These findings, together with a report that the prevalence and activity of BAT is decreased in diabetic patients [22], suggest that BAT may be involved in the etiology of diabetes mellitus and dyslipidemias, independently of and/or secondly to obesity. Thus, BAT may be an intriguing target for combating not only obesity but also some related diseases.
Acknowledgements
This work was supported by Grant-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science, and Technology of Japan (22590227, 24240092), and a Special Research Grant from Tenshi College.

No potential conflict of interest relevant to this article was reported.

  • 1. Cannon B, Nedergaard J. Brown adipose tissue: function and physiological significance. Physiol Rev 2004;84:277-359. ArticlePubMed
  • 2. Lowell BB, Spiegelman BM. Towards a molecular understanding of adaptive thermogenesis. Nature 2000;404:652-660. ArticlePubMedPDF
  • 3. Nedergaard J, Bengtsson T, Cannon B. Unexpected evidence for active brown adipose tissue in adult humans. Am J Physiol Endocrinol Metab 2007;293:E444-E452. ArticlePubMed
  • 4. Ricquier D, Bouillaud F. The uncoupling protein homologues: UCP1, UCP2, UCP3, StUCP and AtUCP. Biochem J 2000;345(Pt 2):161-179. ArticlePubMedPMCPDF
  • 5. Shimizu Y, Nikami H, Saito M. Sympathetic activation of glucose utilization in brown adipose tissue in rats. J Biochem 1991;110:688-692. PubMed
  • 6. Inokuma K, Ogura-Okamatsu Y, Toda C, Kimura K, Yamashita H, Saito M. Uncoupling protein 1 is necessary for norepinephrine-induced glucose utilization in brown adipose tissue. Diabetes 2005;54:1385-1391. ArticlePubMedPDF
  • 7. Himms-Hagen J. Does brown adipose tissue (BAT) have a role in the physiology or treatment of human obesity? Rev Endocr Metab Disord 2001;2:395-401. PubMed
  • 8. Cinti S. The role of brown adipose tissue in human obesity. Nutr Metab Cardiovasc Dis 2006;16:569-574. ArticlePubMed
  • 9. Heaton JM. The distribution of brown adipose tissue in the human. J Anat 1972;112(Pt 1):35-39. PubMedPMC
  • 10. Cohade C, Osman M, Pannu HK, Wahl RL. Uptake in supraclavicular area fat ("USA-Fat"): description on 18F-FDG PET/CT. J Nucl Med 2003;44:170-176. PubMed
  • 11. Garcia CA, Van Nostrand D, Atkins F, Acio E, Butler C, Esposito G, Kulkarni K, Majd M. Reduction of brown fat 2-deoxy-2-[F-18]fluoro-D-glucose uptake by controlling environmental temperature prior to positron emission tomography scan. Mol Imaging Biol 2006;8:24-29. ArticlePubMedPDF
  • 12. Parysow O, Mollerach AM, Jager V, Racioppi S, San Roman J, Gerbaudo VH. Low-dose oral propranolol could reduce brown adipose tissue F-18 FDG uptake in patients undergoing PET scans. Clin Nucl Med 2007;32:351-357. ArticlePubMed
  • 13. Soderlund V, Larsson SA, Jacobsson H. Reduction of FDG uptake in brown adipose tissue in clinical patients by a single dose of propranolol. Eur J Nucl Med Mol Imaging 2007;34:1018-1022. ArticlePubMedPDF
  • 14. Saito M, Okamatsu-Ogura Y, Tsujisaki M, Kaji T, Nakada K. Human brown adipose tissue evaluated by FDG-PET: activation by cold exposure. Int J Obes (Lond) 2007;31(Suppl 1):S32.
  • 15. Saito M, Okamatsu-Ogura Y, Matsushita M, Watanabe K, Yoneshiro T, Nio-Kobayashi J, Iwanaga T, Miyagawa M, Kameya T, Nakada K, Kawai Y, Tsujisaki M. High incidence of metabolically active brown adipose tissue in healthy adult humans: effects of cold exposure and adiposity. Diabetes 2009;58:1526-1531. PubMedPMC
  • 16. van Marken Lichtenbelt WD, Vanhommerig JW, Smulders NM, Drossaerts JM, Kemerink GJ, Bouvy ND, Schrauwen P, Teule GJ. Cold-activated brown adipose tissue in healthy men. N Engl J Med 2009;360:1500-1508. ArticlePubMed
  • 17. Virtanen KA, Lidell ME, Orava J, Heglind M, Westergren R, Niemi T, Taittonen M, Laine J, Savisto NJ, Enerback S, Nuutila P. Functional brown adipose tissue in healthy adults. N Engl J Med 2009;360:1518-1525. ArticlePubMed
  • 18. Yoneshiro T, Aita S, Matsushita M, Okamatsu-Ogura Y, Kameya T, Kawai Y, Miyagawa M, Tsujisaki M, Saito M. Age-related decrease in cold-activated brown adipose tissue and accumulation of body fat in healthy humans. Obesity (Silver Spring) 2011;19:1755-1760. ArticlePubMedPDF
  • 19. Cypess AM, Lehman S, Williams G, Tal I, Rodman D, Goldfine AB, Kuo FC, Palmer EL, Tseng YH, Doria A, Kolodny GM, Kahn CR. Identification and importance of brown adipose tissue in adult humans. N Engl J Med 2009;360:1509-1517. ArticlePubMedPMC
  • 20. Au-Yong IT, Thorn N, Ganatra R, Perkins AC, Symonds ME. Brown adipose tissue and seasonal variation in humans. Diabetes 2009;58:2583-2587. ArticlePubMedPMCPDF
  • 21. Pfannenberg C, Werner MK, Ripkens S, Stef I, Deckert A, Schmadl M, Reimold M, Haring HU, Claussen CD, Stefan N. Impact of age on the relationships of brown adipose tissue with sex and adiposity in humans. Diabetes 2010;59:1789-1793. ArticlePubMedPMCPDF
  • 22. Ouellet V, Routhier-Labadie A, Bellemare W, Lakhal-Chaieb L, Turcotte E, Carpentier AC, Richard D. Outdoor temperature, age, sex, body mass index, and diabetic status determine the prevalence, mass, and glucose-uptake activity of 18F-FDG-detected BAT in humans. J Clin Endocrinol Metab 2011;96:192-199. ArticlePubMedPDF
  • 23. Nedergaard J, Bengtsson T, Cannon B. Three years with adult human brown adipose tissue. Ann N Y Acad Sci 2010;1212:E20-E36. ArticlePubMed
  • 24. Enerback S, Jacobsson A, Simpson EM, Guerra C, Yamashita H, Harper ME, Kozak LP. Mice lacking mitochondrial uncoupling protein are cold-sensitive but not obese. Nature 1997;387:90-94. ArticlePDF
  • 25. Yoneshiro T, Aita S, Matsushita M, Kameya T, Nakada K, Kawai Y, Saito M. Brown adipose tissue, whole-body energy expenditure, and thermogenesis in healthy adult men. Obesity (Silver Spring) 2011;19:13-16. ArticlePubMedPDF
  • 26. Orava J, Nuutila P, Lidell ME, Oikonen V, Noponen T, Viljanen T, Scheinin M, Taittonen M, Niemi T, Enerback S, Virtanen KA. Different metabolic responses of human brown adipose tissue to activation by cold and insulin. Cell Metab 2011;14:272-279. ArticlePubMed
  • 27. Rothwell NJ, Stock MJ. A role for brown adipose tissue in diet-induced thermogenesis. Nature 1979;281:31-35. ArticlePubMedPDF
  • 28. Kozak LP. Brown fat and the myth of diet-induced thermogenesis. Cell Metab 2010;11:263-267. ArticlePubMedPMC
  • 29. Del Mar Gonzalez-Barroso M, Ricquier D, Cassard-Doulcier AM. The human uncoupling protein-1 gene (UCP1): present status and perspectives in obesity research. Obes Rev 2000;1:61-72. ArticlePubMed
  • 30. Rose G, Crocco P, D'Aquila P, Montesanto A, Bellizzi D, Passarino G. Two variants located in the upstream enhancer region of human UCP1 gene affect gene expression and are correlated with human longevity. Exp Gerontol 2011;46:897-904. ArticlePubMed
  • 31. Esterbauer H, Oberkofler H, Liu YM, Breban D, Hell E, Krempler F, Patsch W. Uncoupling protein-1 mRNA expression in obese human subjects: the role of sequence variations at the uncoupling protein-1 gene locus. J Lipid Res 1998;39:834-844. ArticlePubMed
  • 32. Yoneshiro T, Ogawa T, Okamoto N, Matsushita M, Aita S, Kameya T, Kawai Y, Iwanaga T, Saito M. Impact of UCP1 and beta3AR gene polymorphisms on age-related changes in brown adipose tissue and adiposity in humans. Int J Obes (Lond) Epub 2012 Oct 2. DOI: http://dx.doi.org/10.1038/ijo.2012.161.
  • 33. Nagai N, Sakane N, Fujishita A, Fujiwara R, Kimura T, Kotani K, Moritani T. The -3826 A-->G variant of the uncoupling protein-1 gene diminishes thermogenesis during acute cold exposure in healthy children. Obes Res Clin Pract 2007;1:99-107.
  • 34. Nagai N, Sakane N, Ueno LM, Hamada T, Moritani T. The -3826 A-->G variant of the uncoupling protein-1 gene diminishes postprandial thermogenesis after a high fat meal in healthy boys. J Clin Endocrinol Metab 2003;88:5661-5667. PubMed
  • 35. Kontani Y, Wang Y, Kimura K, Inokuma KI, Saito M, Suzuki-Miura T, Wang Z, Sato Y, Mori N, Yamashita H. UCP1 deficiency increases susceptibility to diet-induced obesity with age. Aging Cell 2005;4:147-155. ArticlePubMed
  • 36. Feldmann HM, Golozoubova V, Cannon B, Nedergaard J. UCP1 ablation induces obesity and abolishes diet-induced thermogenesis in mice exempt from thermal stress by living at thermoneutrality. Cell Metab 2009;9:203-209. ArticlePubMed
  • 37. St-Onge MP, Gallagher D. Body composition changes with aging: the cause or the result of alterations in metabolic rate and macronutrient oxidation? Nutrition 2010;26:152-155. ArticlePubMed
  • 38. Cousin B, Cinti S, Morroni M, Raimbault S, Ricquier D, Penicaud L, Casteilla L. Occurrence of brown adipocytes in rat white adipose tissue: molecular and morphological characterization. J Cell Sci 1992;103(Pt 4):931-942. ArticlePubMedPDF
  • 39. Guerra C, Koza RA, Yamashita H, Walsh K, Kozak LP. Emergence of brown adipocytes in white fat in mice is under genetic control. Effects on body weight and adiposity. J Clin Invest 1998;102:412-420. ArticlePubMedPMC
  • 40. Inokuma K, Okamatsu-Ogura Y, Omachi A, Matsushita Y, Kimura K, Yamashita H, Saito M. Indispensable role of mitochondrial UCP1 for antiobesity effect of beta3-adrenergic stimulation. Am J Physiol Endocrinol Metab 2006;290:E1014-E1021. PubMed
  • 41. Petrovic N, Walden TB, Shabalina IG, Timmons JA, Cannon B, Nedergaard J. Chronic peroxisome proliferator-activated receptor gamma (PPARgamma) activation of epididymally derived white adipocyte cultures reveals a population of thermogenically competent, UCP1-containing adipocytes molecularly distinct from classic brown adipocytes. J Biol Chem 2010;285:7153-7164. PubMed
  • 42. Kajimura S, Seale P, Spiegelman BM. Transcriptional control of brown fat development. Cell Metab 2010;11:257-262. ArticlePubMedPMC
  • 43. Seale P, Conroe HM, Estall J, Kajimura S, Frontini A, Ishibashi J, Cohen P, Cinti S, Spiegelman BM. Prdm16 determines the thermogenic program of subcutaneous white adipose tissue in mice. J Clin Invest 2011;121:96-105. ArticlePubMed
  • 44. Wu J, Bostrom P, Sparks LM, Ye L, Choi JH, Giang AH, Khandekar M, Virtanen KA, Nuutila P, Schaart G, Huang K, Tu H, van Marken Lichtenbelt WD, Hoeks J, Enerback S, Schrauwen P, Spiegelman BM. Beige adipocytes are a distinct type of thermogenic fat cell in mouse and human. Cell 2012;150:366-376. ArticlePubMedPMC
  • 45. Lee P, Swarbrick MM, Zhao JT, Ho KK. Inducible brown adipogenesis of supraclavicular fat in adult humans. Endocrinology 2011;152:3597-3602. ArticlePubMedPDF
  • 46. Caterina MJ. Transient receptor potential ion channels as participants in thermosensation and thermoregulation. Am J Physiol Regul Integr Comp Physiol 2007;292:R64-R76. ArticlePubMed
  • 47. Whiting S, Derbyshire E, Tiwari BK. Capsaicinoids and capsinoids A potential role for weight management? A systematic review of the evidence. Appetite 2012;59:341-348. ArticlePubMed
  • 48. Yoneshiro T, Aita S, Kawai Y, Iwanaga T, Saito M. Nonpungent capsaicin analogs (capsinoids) increase energy expenditure through the activation of brown adipose tissue in humans. Am J Clin Nutr 2012;95:845-850. ArticlePubMed
  • 49. Saito M, Yoneshiro T. Capsinoids and related food ingredients activating brown fat thermogenesis and reducing body fat in humans. Curr Opin Lipidol 2013;24:71-77. ArticlePubMed
  • 50. Vallerand AL, Perusse F, Bukowiecki LJ. Cold exposure potentiates the effect of insulin on in vivo glucose uptake. Am J Physiol 1987;253(2 Pt 1):E179-E186. ArticlePubMed
  • 51. Vallerand AL, Perusse F, Bukowiecki LJ. Stimulatory effects of cold exposure and cold acclimation on glucose uptake in rat peripheral tissues. Am J Physiol 1990;259(5 Pt 2):R1043-R1049. ArticlePubMed
  • 52. Shimizu Y, Nikami H, Tsukazaki K, Machado UF, Yano H, Seino Y, Saito M. Increased expression of glucose transporter GLUT-4 in brown adipose tissue of fasted rats after cold exposure. Am J Physiol 1993;264(6 Pt 1):E890-E895. ArticlePubMed
  • 53. Gasparetti AL, de Souza CT, Pereira-da-Silva M, Oliveira RL, Saad MJ, Carneiro EM, Velloso LA. Cold exposure induces tissue-specific modulation of the insulin-signalling pathway in Rattus norvegicus. J Physiol 2003;552(Pt 1):149-162. ArticlePubMedPMCPDF
  • 54. Bartelt A, Bruns OT, Reimer R, Hohenberg H, Ittrich H, Peldschus K, Kaul MG, Tromsdorf UI, Weller H, Waurisch C, Eychmuller A, Gordts PL, Rinninger F, Bruegelmann K, Freund B, Nielsen P, Merkel M, Heeren J. Brown adipose tissue activity controls triglyceride clearance. Nat Med 2011;17:200-205. ArticlePubMedPDF
  • 55. Nishio M, Yoneshiro T, Nakahara M, Suzuki S, Saeki K, Hasegawa M, Kawai Y, Akutsu H, Umezawa A, Yasuda K, Tobe K, Yuo A, Kubota K, Saito M. Production of functional classical brown adipocytes from human pluripotent stem cells using specific hemopoietin cocktail without gene transfer. Cell Metab 2012;16:394-406. ArticlePubMed
Fig. 1
Sympathetically activated thermogenesis in brown adipose tissue, lipid mobilization from white adipose tissue, and induction of beige cells. Sympathetic nerve activity in adipose tissues is increased in response to cold exposure and oral ingestion of some food ingredients through the activation of transient receptor potential channels (TRP). Noradrenaline binds to β-adrenergic receptors (βAR) and initiates signaling cascades for triglyceride (TG) hydrolysis. The released fatty acids activate uncoupling protein 1 (UCP1) and are oxidized to serve as an energy source of thermogenesis. Activated UCP1 uncouples oxidative phosphorylation from ATP synthesis and dissipates energy as heat. Chronic sympathetic activation produces not only brown fat hyperplasia but also an induction of beige cells in white fat, thereby increasing whole-body energy expenditure and decreasing body fat.
dmj-37-22-g001.jpg
Fig. 2
Human brown adipose tissue detected by fluorodeoxyglucose (FDG)-positron emission tomography (PET). FDG uptake into adipose tissue at the supraclavicular and paraspinal regions is detected by PET. The FDG uptake into adipose tissues is negligible under a warm condition at 27℃ (A), but increases greatly after exposure to cold at 19℃ (B) for 2 hours.
dmj-37-22-g002.jpg
Fig. 3
Age-related decrease in brown adipose tissue (BAT) and accumulation of body fat. The activity and prevalence of BAT decrease and body fat increases with age, suggesting the activation and recruitment of BAT as an effective regimen to prevent the age-related development of obesity.
dmj-37-22-g003.jpg

Figure & Data

References

    Citations

    Citations to this article as recorded by  
    • Taraxacum mongolicum polysaccharide promotes white adipocyte browning by regulating miR-134-3p via Akt/GSK-3β signalling
      Xiaoyu Yue, Ling Zhong, Mengyan Ye, Yue Luan, Qiang Zhang, Qin Wang
      International Journal of Biological Macromolecules.2024; 257: 128296.     CrossRef
    • Brown adipose tissue evaluation using water and triglyceride as indices by diffuse reflectance spectroscopy
      Tomomi Iida, Yukio Ueda, Hideo Tsukada, Dai Fukumoto, Takafumi Hamaoka
      Journal of Biophotonics.2024;[Epub]     CrossRef
    • Nuciferine prevents obesity by activating brown adipose tissue
      Chunlong Yan, Yang Zhan, Shouli Yuan, Yujing Cao, Yi Chen, Meng Dong, Hanlin Zhang, Li Chen, Rui Jiang, Wenjun Liu, Wanzhu Jin, Yuanyuan Huang
      Food & Function.2024; 15(2): 967.     CrossRef
    • Effect of Blueberry Supplementation on a Diet-Induced Rat Model of Prediabetes—Focus on Hepatic Lipid Deposition, Endoplasmic Stress Response and Autophagy
      Gonçalo Ferreira, Pedro Vieira, André Alves, Sara Nunes, Inês Preguiça, Tânia Martins-Marques, Tânia Ribeiro, Henrique Girão, Artur Figueirinha, Lígia Salgueiro, Manuela Pintado, Pedro Gomes, Sofia Viana, Flávio Reis
      Nutrients.2024; 16(4): 513.     CrossRef
    • CRISPR/Cas9-mediated inactivation of the phosphatase activity of soluble epoxide hydrolase prevents obesity and cardiac ischemic injury
      Matthieu Leuillier, Thomas Duflot, Séverine Ménoret, Hind Messaoudi, Zoubir Djerada, Déborah Groussard, Raphaël G.P. Denis, Laurence Chevalier, Ahmed Karoui, Baptiste Panthu, Pierre-Alain Thiébaut, Isabelle Schmitz-Afonso, Séverine Nobis, Cynthia Campart,
      Journal of Advanced Research.2023; 43: 163.     CrossRef
    • Metabolic effects of lipectomy and of adipose tissue transplantation
      Sarah Davis, Samantha Hocking, Matthew J. Watt, Jenny E. Gunton
      Obesity.2023; 31(1): 7.     CrossRef
    • Modulation of the thermosensory system by oxytocin
      Ugo Zayan, Laura Caccialupi Da Prato, Françoise Muscatelli, Valéry Matarazzo
      Frontiers in Molecular Neuroscience.2023;[Epub]     CrossRef
    • Regenerative Medicine for Polycystic Ovary Syndrome: Stem Cell-Based Therapies and Brown Adipose Tissue Activation
      Mario Karam, Hélène Najjar, Marwan El Sabban, Aline Hamade, Fadia Najjar
      Stem Cell Reviews and Reports.2023; 19(4): 853.     CrossRef
    • Thermogenic Brown Fat in Humans: Implications in Energy Homeostasis, Obesity and Metabolic Disorders
      Masayuki Saito, Yuko Okamatsu-Ogura
      The World Journal of Men's Health.2023; 41(3): 489.     CrossRef
    • p27Kip1 Deficiency Impairs Brown Adipose Tissue Function Favouring Fat Accumulation in Mice
      Ignacio Colon-Mesa, Neira Sainz, Patricia Corrales, María Collantes, Philipp Kaldis, José Alfredo Martinez, Gema Medina-Gómez, María Jesús Moreno-Aliaga, Xavier Escoté
      International Journal of Molecular Sciences.2023; 24(3): 2664.     CrossRef
    • Energy metabolism and thermoregulation during sleep in young and old females
      Jaehoon Seol, Chihiro Kokudo, Insung Park, Simeng Zhang, Katsuhiko Yajima, Tomohiro Okura, Kumpei Tokuyama
      Scientific Reports.2023;[Epub]     CrossRef
    • Activation of brown adipose tissue by a low-protein diet ameliorates hyperglycemia in a diabetic lipodystrophy mouse model
      Marcos David Munoz, Alexa Zamudio, Maximilian McCann, Victoria Gil, Pingwen Xu, Chong Wee Liew
      Scientific Reports.2023;[Epub]     CrossRef
    • Ado-Mediated Depletion of Taurine Impairs Mitochondrial Respiratory Capacity and Alters the Chromatin Landscape of Inguinal Adipose Tissue
      Pei-Yin Tsai, Bo Shui, Seoyeon Lee, Yang Liu, Yue Qu, Chloe Cheng, Kaydine Edwards, Callie Wong, Ryan Meng-Killeen, Paul D. Soloway, Joeva J. Barrow
      Nutrients.2023; 15(16): 3532.     CrossRef
    • Metabolic associated fatty liver disease is a disease related to sympathetic nervous system activation
      Zhao-Chun Chi
      World Chinese Journal of Digestology.2022; 30(11): 465.     CrossRef
    • Flattening of circadian glucocorticoid oscillations drives acute hyperinsulinemia and adipocyte hypertrophy
      Stefan Tholen, Roma Patel, Agnieszka Agas, Kyle M. Kovary, Atefeh Rabiee, Hayley T. Nicholls, Ewa Bielczyk-Maczyńska, Wenting Yang, Fredric B. Kraemer, Mary N. Teruel
      Cell Reports.2022; 39(13): 111018.     CrossRef
    • KLHL3 deficiency in mice ameliorates obesity, insulin resistance, and nonalcoholic fatty liver disease by regulating energy expenditure
      Ju-hong Jang, Jeong Woong Lee, Min Ji Cho, Byungtae Hwang, Min-Gi Kwon, Dong-Hwan Kim, Nam-Kyung Lee, Jangwook Lee, Young-Jun Park, Yong Ryoul Yang, Jinchul Kim, Yong-Hoon Kim, Tae Hyeon An, Kyoung-Jin Oh, Kwang-Hee Bae, Jong-Gil Park, Jeong-Ki Min
      Experimental & Molecular Medicine.2022; 54(8): 1250.     CrossRef
    • Brown fat-associated postprandial thermogenesis in humans: Different effects of isocaloric meals rich in carbohydrate, fat, and protein
      Sayuri Aita, Mami Matsushita, Takeshi Yoneshiro, Takuya Hatano, Toshimitsu Kameya, Iwao Ohkubo, Masayuki Saito
      Frontiers in Nutrition.2022;[Epub]     CrossRef
    • Association of apolipoprotein M and sphingosine-1-phosphate with brown adipose tissue after cold exposure in humans
      Anna Borup, Ida Donkin, Mariëtte R. Boon, Martin Frydland, Borja Martinez-Tellez, Annika Loft, Sune H. Keller, Andreas Kjaer, Jesper Kjaergaard, Christian Hassager, Romain Barrès, Patrick C. N. Rensen, Christina Christoffersen
      Scientific Reports.2022;[Epub]     CrossRef
    • Signaling Pathways Regulating Thermogenesis
      Chihiro Tabuchi, Hei Sook Sul
      Frontiers in Endocrinology.2021;[Epub]     CrossRef
    • Overexpression of translationally controlled tumor protein ameliorates metabolic imbalance and increases energy expenditure in mice
      Yejin Jeon, Ji-Young Choi, Eun-Hwa Jang, Je Kyung Seong, Kyunglim Lee
      International Journal of Obesity.2021; 45(7): 1576.     CrossRef
    • Diurnal variations of brown fat thermogenesis and fat oxidation in humans
      Mami Matsushita, Shinsuke Nirengi, Masanobu Hibi, Hitoshi Wakabayashi, Sang-il Lee, Masayuki Domichi, Naoki Sakane, Masayuki Saito
      International Journal of Obesity.2021; 45(11): 2499.     CrossRef
    • Adipose browning response to burn trauma is impaired with aging
      Abdikarim Abdullahi, Carly M. Knuth, Christopher Auger, Thibacg Sivayoganathan, Alexandra Parousis, Marc G. Jeschke
      JCI Insight.2021;[Epub]     CrossRef
    • The Effect of Hyperbaric Therapy on Brown Adipose Tissue in Rats
      Chang-Hyung Lee, Young-A Choi, Sung-Jin Heo, Parkyong Song
      International Journal of Environmental Research and Public Health.2021; 18(17): 9165.     CrossRef
    • Brown Fat as a Regulator of Systemic Metabolism beyond Thermogenesis
      Okamatsu-Ogura Yuko, Masayuki Saito
      Diabetes & Metabolism Journal.2021; 45(6): 840.     CrossRef
    • Comparative Transcriptome Profiling of Young and Old Brown Adipose Tissue Thermogenesis
      Yumin Kim, Baeki E. Kang, Dongryeol Ryu, So Won Oh, Chang-Myung Oh
      International Journal of Molecular Sciences.2021; 22(23): 13143.     CrossRef
    • Supplementation of polar lipids‐enriched milk fat globule membrane in high‐fat diet‐fed rats during pregnancy and lactation promotes brown/beige adipocyte development and prevents obesity in male offspring
      Tiange Li, Han Gong, Qichen Yuan, Min Du, Fazheng Ren, Xueying Mao
      The FASEB Journal.2020; 34(3): 4619.     CrossRef
    • Nicotine exposure during breastfeeding reduces sympathetic activity in brown adipose tissue and increases in white adipose tissue in adult rats: Sex-related differences
      T.C. Peixoto, E.G. Moura, P.N. Soares, I.M. Bertasso, C.B. Pietrobon, F.A.H. Caramez, R.A. Miranda, E. Oliveira, A.C. Manhães, P.C. Lisboa
      Food and Chemical Toxicology.2020; 140: 111328.     CrossRef
    • Brown Adipose Expansion and Remission of Glycemic Dysfunction in Obese SM/J Mice
      Caryn Carson, Juan F. Macias-Velasco, Subhadra Gunawardana, Mario A. Miranda, Sakura Oyama, Celine L. St. Pierre, Heather Schmidt, Jessica P. Wayhart, Heather A. Lawson
      Cell Reports.2020; 33(1): 108237.     CrossRef
    • Urolithin A Induces Brown-like Phenotype in 3T3-L1 White Adipocytes via β3-adrenergic Receptor-p38 MAPK Signaling Pathway
      Subramani Manigandan, Jong Won Yun
      Biotechnology and Bioprocess Engineering.2020; 25(3): 345.     CrossRef
    • Brown Adipose Tissue, Diet-Induced Thermogenesis, and Thermogenic Food Ingredients: From Mice to Men
      Masayuki Saito, Mami Matsushita, Takeshi Yoneshiro, Yuko Okamatsu-Ogura
      Frontiers in Endocrinology.2020;[Epub]     CrossRef
    • Differences in [18F]FDG uptake in BAT of UCP1 −/− and UCP1 +/+ during adrenergic stimulation of non-shivering thermogenesis
      Christian T. McHugh, John Garside, Jared Barkes, Jonathan Frank, Constance Dragicevich, Hong Yuan, Rosa T. Branca
      EJNMMI Research.2020;[Epub]     CrossRef
    • Glucocorticoids and Brown Adipose Tissue: Do glucocorticoids really inhibit thermogenesis?
      Ineke H.N. Luijten, Barbara Cannon, Jan Nedergaard
      Molecular Aspects of Medicine.2019; 68: 42.     CrossRef
    • Sexual Dimorphism of Brown Adipose Tissue Function
      Lindsay J. Robinson, James Law, Valerie Astle, Marta Gutiérrez-García, Shalini Ojha, Michael E. Symonds, Nicola Pitchford, Helen Budge
      The Journal of Pediatrics.2019; 210: 166.     CrossRef
    • Cold Induced Depot-Specific Browning in Ferret Aortic Perivascular Adipose Tissue
      Bàrbara Reynés, Evert M. van Schothorst, Jaap Keijer, Enzo Ceresi, Paula Oliver, Andreu Palou
      Frontiers in Physiology.2019;[Epub]     CrossRef
    • Continuous intake of Trehalose induces white adipose tissue Browning and Enhances energy metabolism
      Chikako Arai, Norie Arai, Shigeyuki Arai, Chiyo Yoshizane, Satomi Miyata, Akiko Mizote, Aki Suyama, Shin Endo, Toshio Ariyasu, Hitoshi Mitsuzumi, Shimpei Ushio
      Nutrition & Metabolism.2019;[Epub]     CrossRef
    • Sclareol-loaded lipid nanoparticles improved metabolic profile in obese mice
      Gabriela Cavazza Cerri, Leandro Ceotto Freitas Lima, Deborah de Farias Lelis, Lucíola da Silva Barcelos, John David Feltenberger, Samuel Vidal Mussi, Renato Sobral Monteiro-Junior, Robson Augusto Souza dos Santos, Lucas Antônio Miranda Ferreira, Sérgio He
      Life Sciences.2019; 218: 292.     CrossRef
    • Resveratrol regulates skeletal muscle fibers switching through the AdipoR1-AMPK-PGC-1α pathway
      Qinyang Jiang, Xiaofang Cheng, Yueyue Cui, Qin Xia, Xueyu Yan, Mingyuan Zhang, Ganqiu Lan, Jiaqi Liu, Tizhong Shan, Yanna Huang
      Food & Function.2019; 10(6): 3334.     CrossRef
    • Regulation of Systemic Glucose Homeostasis by T Helper Type 2 Cytokines
      Yea Eun Kang, Hyun Jin Kim, Minho Shong
      Diabetes & Metabolism Journal.2019; 43(5): 549.     CrossRef
    • Inter‐organ communication: a gatekeeper for metabolic health
      Judit Castillo‐Armengol, Lluis Fajas, Isabel C Lopez‐Mejia
      EMBO reports.2019;[Epub]     CrossRef
    • Clinical Implications of UCP1 mRNA Expression in Human Cervical Adipose Tissue Under Physiological Conditions
      Ju Hee Lee, Ji Min Kim, Min Jeong Choi, Yea Eun Kang, Kyoung Hye Joung, Hyon‐Seung Yi, Koon Soon Kim, Bon Jeong Ku, Bon Seok Koo, Minho Shong, Hyun Jin Kim
      Obesity.2018; 26(6): 1008.     CrossRef
    • Lysophosphatidic Acid Signaling in Obesity and Insulin Resistance
      Kenneth D’Souza, Geena Paramel, Petra Kienesberger
      Nutrients.2018; 10(4): 399.     CrossRef
    • Invalidation of Microsomal Prostaglandin E Synthase-1 (mPGES-1) Reduces Diet-Induced Low-Grade Inflammation and Adiposity
      Clément Pierre, Florent Guillebaud, Coraline Airault, Nathalie Baril, Rym Barbouche, Etienne Save, Stéphanie Gaigé, Bruno Bariohay, Michel Dallaporta, Jean-Denis Troadec
      Frontiers in Physiology.2018;[Epub]     CrossRef
    • Bovine lactoferrin promotes energy expenditure via the cAMP-PKA signaling pathway in human reprogrammed brown adipocytes
      Kanae Nakamura, Tsunao Kishida, Akika Ejima, Riho Tateyama, Satoru Morishita, Tomoji Ono, Michiaki Murakoshi, Keikichi Sugiyama, Hoyoku Nishino, Osam Mazda
      BioMetals.2018; 31(3): 415.     CrossRef
    • Association of wrist and ambient temperature with cold-induced brown adipose tissue and skeletal muscle [18F]FDG uptake in young adults
      Borja Martinez-Tellez, Huiwen Xu, Guillermo Sanchez-Delgado, Francisco M. Acosta, Patrick C. N. Rensen, Jose M. Llamas-Elvira, Jonatan R. Ruiz
      American Journal of Physiology-Regulatory, Integrative and Comparative Physiology.2018; 315(6): R1281.     CrossRef
    • Secretin-Activated Brown Fat Mediates Prandial Thermogenesis to Induce Satiation
      Yongguo Li, Katharina Schnabl, Sarah-Madeleine Gabler, Monja Willershäuser, Josefine Reber, Angelos Karlas, Sanna Laurila, Minna Lahesmaa, Mueez u Din, Andrea Bast-Habersbrunner, Kirsi A. Virtanen, Tobias Fromme, Florian Bolze, Libbey S. O’Farrell, Jorge
      Cell.2018; 175(6): 1561.     CrossRef
    • Effects of lobeglitazone, a novel thiazolidinedione, on adipose tissue remodeling and brown and beige adipose tissue development in db/db mice
      G Kim, Y-h Lee, M R Yun, J-Y Lee, E G Shin, B-W Lee, E S Kang, B-S Cha
      International Journal of Obesity.2018; 42(3): 542.     CrossRef
    • Cellular Aging Contributes to Failure of Cold-Induced Beige Adipocyte Formation in Old Mice and Humans
      Daniel C. Berry, Yuwei Jiang, Robert W. Arpke, Elizabeth L. Close, Aki Uchida, David Reading, Eric D. Berglund, Michael Kyba, Jonathan M. Graff
      Cell Metabolism.2017; 25(1): 166.     CrossRef
    • Postprandial Increase in Energy Expenditure Correlates with Body Weight Reduction in Patients with Type 2 Diabetes Receiving Diet Therapy
      Daisuke Sanoyama, Mototsugu Nagao, Akira Asai, Yuko Nakamura, Kazumi Sato, Yasushi Nakajima, Shinichi Oikawa, Hitoshi Sugihara
      Journal of Atherosclerosis and Thrombosis.2017; 24(4): 422.     CrossRef
    • Physiological regulation and metabolic role of browning in white adipose tissue
      Aleksandra Jankovic, Vesna Otasevic, Ana Stancic, Biljana Buzadzic, Aleksandra Korac, Bato Korac
      Hormone Molecular Biology and Clinical Investigation.2017;[Epub]     CrossRef
    • Resveratrol enhances brown adipocyte formation and function by activating AMP‐activated protein kinase (AMPK) α1 in mice fed high‐fat diet
      Songbo Wang, Xingwei Liang, Qiyuan Yang, Xing Fu, Meijun Zhu, B. D. Rodgers, Qingyan Jiang, Michael V. Dodson, Min Du
      Molecular Nutrition & Food Research.2017;[Epub]     CrossRef
    • The Role of the Autonomic Nervous System in the Pathophysiology of Obesity
      Daniela Guarino, Monica Nannipieri, Giorgio Iervasi, Stefano Taddei, Rosa Maria Bruno
      Frontiers in Physiology.2017;[Epub]     CrossRef
    • Adipoz doku ve enerji metabolizması üzerine etkileri
      Meltem Mermer, Nilüfer Acar TEK
      SDÜ Sağlık Bilimleri Dergisi.2017;[Epub]     CrossRef
    • Experimental evidence reveals the UCP1 genotype changes the oxygen consumption attributed to non-shivering thermogenesis in humans
      Takayuki Nishimura, Takafumi Katsumura, Midori Motoi, Hiroki Oota, Shigeki Watanuki
      Scientific Reports.2017;[Epub]     CrossRef
    • Distinct cellular and molecular mechanisms for β3 adrenergic receptor-induced beige adipocyte formation
      Yuwei Jiang, Daniel C Berry, Jonathan M Graff
      eLife.2017;[Epub]     CrossRef
    • Ovarian hormones and obesity
      Brigitte Leeners, Nori Geary, Philippe N. Tobler, Lori Asarian
      Human Reproduction Update.2017; 23(3): 300.     CrossRef
    • Nutritional approaches for managing obesity-associated metabolic diseases
      Rachel Botchlett, Shih-Lung Woo, Mengyang Liu, Ya Pei, Xin Guo, Honggui Li, Chaodong Wu
      Journal of Endocrinology.2017; 233(3): R145.     CrossRef
    • Lower core body temperature and greater body fat are components of a human thrifty phenotype
      M Reinhardt, M Schlögl, S Bonfiglio, S B Votruba, J Krakoff, M S Thearle
      International Journal of Obesity.2016; 40(5): 754.     CrossRef
    • Lipopolysaccharide-binding protein is a negative regulator of adipose tissue browning in mice and humans
      Aleix Gavaldà-Navarro, José M. Moreno-Navarrete, Tania Quesada-López, Montserrat Cairó, Marta Giralt, José M. Fernández-Real, Francesc Villarroya
      Diabetologia.2016; 59(10): 2208.     CrossRef
    • Mouse strains to study cold-inducible beige progenitors and beige adipocyte formation and function
      Daniel C. Berry, Yuwei Jiang, Jonathan M. Graff
      Nature Communications.2016;[Epub]     CrossRef
    • Control of human energy expenditure by cytochrome c oxidase subunit IV-2
      Tomas A. Schiffer, Maria Peleli, Michaela L. Sundqvist, Björn Ekblom, Jon O. Lundberg, Eddie Weitzberg, Filip J. Larsen
      American Journal of Physiology-Cell Physiology.2016; 311(3): C452.     CrossRef
    • Susceptibility of brown adipocytes to pro-inflammatory cytokine toxicity and reactive oxygen species
      Lars Rebiger, Sigurd Lenzen, Ilir Mehmeti
      Bioscience Reports.2016;[Epub]     CrossRef
    • Short-term Cold Acclimation Recruits Brown Adipose Tissue in Obese Humans
      Mark J.W. Hanssen, Anouk A.J.J. van der Lans, Boudewijn Brans, Joris Hoeks, Kelly M.C. Jardon, Gert Schaart, Felix M. Mottaghy, Patrick Schrauwen, Wouter D. van Marken Lichtenbelt
      Diabetes.2016; 65(5): 1179.     CrossRef
    • Phytochemicals as novel agents for the induction of browning in white adipose tissue
      Yusra Azhar, Ashish Parmar, Colette N. Miller, Janaiya S. Samuels, Srujana Rayalam
      Nutrition & Metabolism.2016;[Epub]     CrossRef
    • Energy expenditure and intake during puberty in healthy nonobese adolescents: a systematic review
      Hoi Lun Cheng, Mazen Amatoury, Katharine Steinbeck
      The American Journal of Clinical Nutrition.2016; 104(4): 1061.     CrossRef
    • MRI characterization of brown adipose tissue in obese and normal-weight children
      Jie Deng, Samantha E. Schoeneman, Huiyuan Zhang, Soyang Kwon, Cynthia K. Rigsby, Richard M. Shore, Jami L. Josefson
      Pediatric Radiology.2015; 45(11): 1682.     CrossRef
    • A Human Thrifty Phenotype Associated With Less Weight Loss During Caloric Restriction
      Martin Reinhardt, Marie S. Thearle, Mostafa Ibrahim, Maximilian G. Hohenadel, Clifton Bogardus, Jonathan Krakoff, Susanne B. Votruba
      Diabetes.2015; 64(8): 2859.     CrossRef
    • Resveratrol induces brown-like adipocyte formation in white fat through activation of AMP-activated protein kinase (AMPK) α1
      S Wang, X Liang, Q Yang, X Fu, C J Rogers, M Zhu, B D Rodgers, Q Jiang, M V Dodson, M Du
      International Journal of Obesity.2015; 39(6): 967.     CrossRef
    • Brown Adipose Tissue as a Therapeutic Target for Obesity: From Mice to Humans
      Masayuki Saito
      The Korean Journal of Obesity.2015; 24(1): 1.     CrossRef
    • Isoproterenol Increases Uncoupling, Glycolysis, and Markers of Beiging in Mature 3T3-L1 Adipocytes
      Colette N. Miller, Jeong-Yeh Yang, Emily England, Amelia Yin, Clifton A. Baile, Srujana Rayalam, Graça Soveral
      PLOS ONE.2015; 10(9): e0138344.     CrossRef
    • Carotenoids and their conversion products in the control of adipocyte function, adiposity and obesity
      M. Luisa Bonet, Jose A. Canas, Joan Ribot, Andreu Palou
      Archives of Biochemistry and Biophysics.2015; 572: 112.     CrossRef
    • Calorie hoarding and thrifting: Foxa3 finds a way
      Xinran Ma, Lingyan Xu, Elisabetta Mueller
      Adipocyte.2015; 4(4): 325.     CrossRef
    • Can thermogenic adipocytes protect from obesity?
      L. N. Medvedev, E. I. Elsukova
      Journal of Physiology and Biochemistry.2015; 71(4): 847.     CrossRef
    • Capsinoids suppress diet-induced obesity through uncoupling protein 1-dependent mechanism in mice
      Yuko Okamatsu-Ogura, Ayumi Tsubota, Kana Ohyama, Yoshihito Nogusa, Masayuki Saito, Kazuhiro Kimura
      Journal of Functional Foods.2015; 19: 1.     CrossRef
    • Energy Expenditure in Humans and Other Primates: A New Synthesis
      Herman Pontzer
      Annual Review of Anthropology.2015; 44(1): 169.     CrossRef
    • Gene expression of peripheral blood mononuclear cells is affected by cold exposure
      Bàrbara Reynés, Estefanía García-Ruiz, Paula Oliver, Andreu Palou
      American Journal of Physiology-Regulatory, Integrative and Comparative Physiology.2015; 309(8): R824.     CrossRef
    • Ambient Temperature and Prevalence of Obesity: A Nationwide Population-Based Study in Korea
      Hae Kyung Yang, Kyungdo Han, Jae-Hyoung Cho, Kun-Ho Yoon, Bong-Yun Cha, Seung-Hwan Lee, David Meyre
      PLOS ONE.2015; 10(11): e0141724.     CrossRef
    • Food Ingredients as Anti-Obesity Agents
      Masayuki Saito, Takeshi Yoneshiro, Mami Matsushita
      Trends in Endocrinology & Metabolism.2015; 26(11): 585.     CrossRef
    • Matured Hop Bittering Components Induce Thermogenesis in Brown Adipose Tissue via Sympathetic Nerve Activity
      Yumie Morimoto-Kobayashi, Kazuaki Ohara, Chika Takahashi, Sayoko Kitao, Guanying Wang, Yoshimasa Taniguchi, Mikio Katayama, Katsuya Nagai, Qinghua Sun
      PLOS ONE.2015; 10(6): e0131042.     CrossRef
    • Role of forkhead box protein A3 in age-associated metabolic decline
      Xinran Ma, Lingyan Xu, Oksana Gavrilova, Elisabetta Mueller
      Proceedings of the National Academy of Sciences.2014; 111(39): 14289.     CrossRef
    • Thermoneutrality results in prominent diet‐induced body weight differences in C57BL/6J mice, not paralleled by diet‐induced metabolic differences
      Femke P. M. Hoevenaars, Melissa Bekkenkamp‐Grovenstein, Rolf J. R. J. Janssen, Sandra G. Heil, Annelies Bunschoten, Elise F. Hoek‐van den Hil, Sophie Snaas‐Alders, Katja Teerds, Evert M. van Schothorst, Jaap Keijer
      Molecular Nutrition & Food Research.2014; 58(4): 799.     CrossRef
    • Vijftig tinten vet
      Mattees van Dijk
      Tijdschrift voor praktijkondersteuning.2014; 9(6): 170.     CrossRef
    • MRI detection of brown adipose tissue with low fat content in newborns with hypothermia
      Houchun H. Hu, Tai-Wei Wu, Larry Yin, Mimi S. Kim, Jonathan M. Chia, Thomas G. Perkins, Vicente Gilsanz
      Magnetic Resonance Imaging.2014; 32(2): 107.     CrossRef
    • The origin and definition of brite versus white and classical brown adipocytes
      Matthias Rosenwald, Christian Wolfrum
      Adipocyte.2014; 3(1): 4.     CrossRef
    • Expression of “brown-in-white” adipocyte biomarkers shows gender differences and the influence of early dietary exposure
      María Servera, Nora López, Francisca Serra, Andreu Palou
      Genes & Nutrition.2014;[Epub]     CrossRef
    • Temperature-Acclimated Brown Adipose Tissue Modulates Insulin Sensitivity in Humans
      Paul Lee, Sheila Smith, Joyce Linderman, Amber B. Courville, Robert J. Brychta, William Dieckmann, Charlotte D. Werner, Kong Y. Chen, Francesco S. Celi
      Diabetes.2014; 63(11): 3686.     CrossRef
    • Food Function Study of Obesity and Fat Energy Metabolism
      Teruo Kawada
      Nippon Eiyo Shokuryo Gakkaishi.2014; 67(3): 119.     CrossRef
    • Kaempferia parviflora extract increases energy consumption through activation of BAT in mice
      Susumu Yoshino, Minji Kim, Riyo Awa, Hiroshige Kuwahara, Yuriko Kano, Teruo Kawada
      Food Science & Nutrition.2014; 2(6): 634.     CrossRef
    • Extensive hypermetabolic pattern of brown adipose tissue activation on 18F-FDG PET/CT in a patient diagnosed of catecholamine-secreting para-vesical paraganglioma
      J. Banzo, M.A. Ubieto, M.F. Berisa, A. Andrés, M.L. Mateo, L. Tardín, A. Parra, P. Razola, E. Prats
      Revista Española de Medicina Nuclear e Imagen Molecular (English Edition).2013; 32(6): 397.     CrossRef
    • Ghrelin
      Geetali Pradhan, Susan L. Samson, Yuxiang Sun
      Current Opinion in Clinical Nutrition and Metabolic Care.2013; 16(6): 619.     CrossRef
    • Transient receptor potential activated brown fat thermogenesis as a target of food ingredients for obesity management
      Takeshi Yoneshiro, Masayuki Saito
      Current Opinion in Clinical Nutrition and Metabolic Care.2013; 16(6): 625.     CrossRef
    • Extensive hypermetabolic pattern of brown adipose tissue activation on 18F-FDG PET/CT in a patient diagnosed of catecholamine-secreting para-vesical paraganglioma
      J. Banzo, M.A. Ubieto, M.F. Berisa, A. Andrés, M.L. Mateo, L. Tardín, A. Parra, P. Razola, E. Prats
      Revista Española de Medicina Nuclear e Imagen Molecular.2013; 32(6): 397.     CrossRef

    • PubReader PubReader
    • Cite
      CITE
      export Copy
      Close
      Download Citation
      Download a citation file in RIS format that can be imported by all major citation management software, including EndNote, ProCite, RefWorks, and Reference Manager.

      Format:
      • RIS — For EndNote, ProCite, RefWorks, and most other reference management software
      • BibTeX — For JabRef, BibDesk, and other BibTeX-specific software
      Include:
      • Citation for the content below
      Brown Adipose Tissue as a Regulator of Energy Expenditure and Body Fat in Humans
      Diabetes Metab J. 2013;37(1):22-29.   Published online February 15, 2013
      Close
    • XML DownloadXML Download
    Figure

    Diabetes Metab J : Diabetes & Metabolism Journal