Thus, although BAT represents a small fraction of body mass (0.1%), increasing BAT activity is an upcoming promising therapeutic strategy to treat obesity [26]. Fuller-Jackson, J.-P.; Dordevic, A.L. Various physiological conditions may influence BAT activity in humans: cold, circadian rhythms, and exercise [, In humans, several studies have shown that fish oil supplementation does not reduce body weight, but some studies indicate that it may have effects in reducing fat mass. NE, through -adrenergic receptors, stimulates thermogenesis by brown adipose tissue, and optimal responsiveness of this tissue to NE is dependent on thyroid hormone.269,270 Brown adipose tissue is rich in mitochondria containing a unique 32-kd protein (thermogenin) that uncouples oxidation and phosphorylation of adenosine diphosphate, reduces ATP production, and consequently enhances thermogenesis.269,271 Thermogenin is T3 dependent, and brown adipose tissue contains a 5-monoiodothyronine deiodinase that deiodinates T4 locally to T3.269,271 Full maturation of catecholamine-stimulated cellular respiration in brown adipose tissue occurs before delivery in the ovine fetus and requires thyroid hormone.269,272 Fetal thyroidectomy in this species leads to marked hypothermia, with low plasma free fatty acid levels and increased plasma epinephrine concentrations.272 In vitro, basal brown adipose tissue thermogenesis and NE-stimulated and dibutyryl cAMP-stimulated thermogenesis are decreased by fetal thyroidectomy. ; Kidanto, H.; et al. It is now accepted that brown adipose tissue is found to some extent in a majority of adult humans throughout the greater part of life and influences not only cold sensitivity, but also body weight regulation. ; Souza-Mello, V.; Mandarim-de-Lacerda, C.A. The largest accumulations of brown adipose tissue envelop the kidneys and adrenal glands, and smaller amounts surround the blood vessels of the mediastinum and neck.269 The mass of brown adipose tissue peaks at the time of birth and gradually decreases during the early weeks of life. Fang, C.; Kim, H.; Yanagisawa, L.; Bennett, W.; Sirven, M.A. Cold is one of the most potent activators of BAT function, and the effect of cold is mediated via the activated sympathetic nervous system. ; Roy, D.; Pilon, G.; Dudonn, S.; Matamoros, S.; Varin, T.V. ; Isolauri, E.; Laitinen, K.; Salminen, S. Effect of Mothers Weight on Infants Microbiota Acquisition, Composition, and Activity during Early Infancy: A Prospective Follow-up Study Initiated in Early Pregnancy. The Impact of Long Chain N-3 Polyunsaturated Fatty Acid Supplementation on Inflammation, Insulin Sensitivity and CVD Risk in a Group of Overweight Women with an Inflammatory Phenotype. Maric-Bilkan, C.; Symonds, M.; Ozanne, S.; Alexander, B.T. For ; Marcos, A.; Rueda, R.; McArdle, H.J. Several factors are involved in the regulation of BAT function, and manipulation of these factors is under intense investigation. prior to publication. Alisi, A.; Bedogni, G.; Baviera, G.; Giorgio, V.; Porro, E.; Paris, C.; Giammaria, P.; Reali, L.; Anania, F.; Nobili, V. Randomised Clinical Trial: The Beneficial Effects of VSL#3 in Obese Children with Non-Alcoholic Steatohepatitis. The preponderance of evidence indicates that neural signaling to aging brown fat is intact in the senescent animals. Maternal Smoking during Pregnancy and DNA-Methylation in Children at Age 5.5 Years: Epigenome-Wide-Analysis in the European Childhood Obesity Project (CHOP)-Study. Hui, S.C.N. (2003) Norepinephrine release in brown adipose tissue remains robust in cold-exposed senescent Fischer 344 rats. Gao, Z.; Yin, J.; Zhang, J. Butyrate improves insulin sensitivity and increases energy expenditure in mice. ; Chen, Y.-M.; Chen, W.-Q. ; Zhu, M.J.; Du, M. Maternal High-Fat Diet during Lactation Impairs Thermogenic Function of Brown Adipose Tissue in Offspring Mice. ; Scherer, P.E. Zoico, E.; Rubele, S.; De Caro, A.; Nori, N.; Mazzali, G.; Fantin, F.; Rossi, A.; Zamboni, M. Brown and Beige Adipose Tissue and Aging. ; Aldiss, P.; Pope, M.; Budge, H. Recent Advances in Our Understanding of Brown and Beige Adipose Tissue: The Good Fat That Keeps You Healthy. Catecholamines, via -adrenergic receptors, stimulate fatty acid oxidation and thermogenesis. Editors select a small number of articles recently published in the journal that they believe will be particularly ; Martnez, I. Prebiotics Reduce Body Fat and Alter Intestinal Microbiota in Children Who Are Overweight or With Obesity. Moreno-Navarrete, J.M. Gilsanz, V.; Chung, S.A.; Jackson, H.; Dorey, F.J.; Hu, H.H. ; Alberici, L.C. ; Pesonen, U.; Koulu, M. Prenatal Metformin Exposure in a Maternal High Fat Diet Mouse Model Alters the Transcriptome and Modifies the Metabolic Responses of the Offspring. Mitochondria in brown adipose tissue express a unique protein, thermogenin (or UCP, uncoupling protein), which uncouples oxidation from subsequent adenosine diphosphate phosphorylation and thereby promotes the release of heat. The Gut Microbiota Modulates Both Browning of White Adipose Tissue and the Activity of Brown Adipose Tissue. Huang, F.; Zhao, R.; Xia, M.; Shen, G.X. Son, J.S. ; Furtner, F.; Rivara, F.P. Sanchis-Chord, J.; Del Pulgar, E.M.G. ; Bloor, I.; Ojha, S.; Budge, H. The Placenta, Maternal Diet and Adipose Tissue Development in the Newborn. ; Shen, M.; Yadav, H. Novel Browning Agents, Mechanisms, and Therapeutic Potentials of Brown Adipose Tissue. ; Calvino, C.; Santos, T.R. Wang, H.; Chen, Y.; Mao, X.; Du, M. Maternal Obesity Impairs Fetal Mitochondriogenesis and Brown Adipose Tissue Development Partially via Upregulation of MiR-204-5p. Plasma Docosahexaenoic Acid and Eicosapentaenoic Acid Concentrations Are Positively Associated with Brown Adipose Tissue Activity in Humans. UCP1 is a BAT-specific protein located in the inner mitochondrial membrane, which uncouples the respiratory chain, producing heat instead of energy. This has been suggested by animal studies [, BAT quantity has been inversely correlated with BMI making it a possible anti-obesity target [, As it is part of all these biological processes, BAT affects the individuals health at different levels (metabolic, structural, functional), thus, it is fundamental to understand whether and how we can modulate it during childhood to obtain health benefits in future. Brown fat thermogenesis potential as measured by UCP1 concentration does not change with age. Association between Maternal Adherence to Healthy Lifestyle Practices and Risk of Obesity in Offspring: Results from Two Prospective Cohort Studies of Mother-Child Pairs in the United States. Biopsies of areas of UCP1 activity identified by positron emission tomography or computed tomography provided histologic confirmation of the presence of supraclavicular BAT.133,134 UCP1 activity was stimulated by cold exposure.135 Another study in humans documented a very strong seasonal variation in the presence of BAT.136 It is possible that altered regulation of BAT activity is involved in the pathogenesis of obesity. Zhang, C.-X. Fabbiano, S.; Surez-Zamorano, N.; Chevalier, C. Functional Gut Microbiota Remodeling Contributes to the Caloric Restriction-Induced Metabolic Improvements. ; Rundle, A.G.; Woodcroft, K.J. Rzehak, P.; Hellmuth, C.; Uhl, O.; Kirchberg, F.F. Unfortunately, the majority of the studies so far performed have been conducted in animal models that have different features compared to humans [, The main factors contributing to the growth of the adipose cells have been found to be strictly connected and involved in the so-called microbiome-immune-metabolic axis, a series of connections between the gut microbiome, the immune system and metabolic organs as adipose tissue [, One of the most studied contributors in fetal adiposity development is the maternal gestational weight gain. Salvini, S.; Parpinel, M.; Gnagnarella, P.; Maisonneuve, P.; Turrini, A. Albracht-Schulte, K.; Kalupahana, N.S. ; Dechandt, C.R.P. Flachs, P.; Rhl, R.; Hensler, M. Synergistic Induction of Lipid Catabolism and Anti-Inflammatory Lipids in White Fat of Dietary Obese Mice in Response to Calorie Restriction and n-3 Fatty Acids. Moreno-Navarrete, J.M. Babies have this fat around their necks, chests,backs, and butts, and it acts kind of like a big scarf to keep them warm. UCP1 is found primarily in classic depots of brown adipose tissue, notably periaortic, cervical, interscapular, and perirenal, in the human infant. Fleckenstein-Elsen, M.; Dinnies, D.; Jelenik, T.; Roden, M.; Romacho, T.; Eckel, J. Eicosapentaenoic Acid and Arachidonic Acid Differentially Regulate Adipogenesis, Acquisition of a Brite Phenotype and Mitochondrial Function in Primary Human Adipocytes. ; Shadrach, J.L. ; Pauls, S.D. The authors are grateful to Beatrice Ravanelli for scientific discussion. Effects of Hormonal Status. ; Lauritzen, L. Fish Oil as a Potential Activator of Brown and Beige Fat Thermogenesis. Papers are submitted upon individual invitation or recommendation by the scientific editors and undergo peer review Fenzl, A.; Kiefer, F.W. ; Teodoro, B.G. Surgical removal of this tissue leads to neonatal hypothermia. ; Talcott, S.T. Entringer, S.; Rasmussen, J.; Cooper, D.M. ; Unal, R. Omega-3 Fatty Acids Reduce Adipose Tissue Macrophages in Human Subjects with Insulin Resistance. Pediatric obesity is a significant challenge for our society [, Obesity has a multifactorial pathogenesis, different factors such as genetic, psychosocial and environmental ones, and in particular chronic energy imbalance, may influence its onset [. Aldiss, P.; Dellschaft, N.S. Find support for a specific problem in the support section of our website. This brown adipose tissue, a.k.a. In fact, gut microbiota exacerbates metabolic inflammation through increased Toll-like receptors in the systemic circulation and WAT inflammation in mice fed with lard diet compared to mice fed with fish oil [. Claycombe, K.J. ; Roemmich, J.N. ; Hamner, H.C.; Li, R.; Perrine, C.G. ; Pope, M.; Sacks, H.; Budge, H. Brown Adipose Tissue Development and Function and Its Impact on Reproduction. Mendona, A.M.; Cayer, L.G.J. NE, through -adrenergic receptors, stimulates thermogenesis by brown adipose tissue, and optimal responsiveness of this tissue to NE is dependent on thyroid hormone.412,413 Brown adipose tissue is rich in mitochondria, containing a unique 32-kDa protein (thermogenin) that uncouples oxidation and phosphorylation of adenosine diphosphate, reduces ATP production, and consequently enhances thermogenesis.412,414 Thermogenin is T3 dependent, and brown adipose tissue contains a 5-monoiodothyronine deiodinase that deiodinates T4 locally to T3.412,414 Full maturation of catecholamine-stimulated cellular respiration in brown adipose tissue occurs before delivery in the ovine fetus and requires thyroid hormone.412,415 Fetal thyroidectomy in this species leads to marked hypothermia, with low plasma free fatty acid levels and increased plasma epinephrine concentrations.415 In vitro, basal brown adipose tissue thermogenesis and NE-stimulated and dibutyryl cAMP-stimulated thermogenesis are decreased by fetal thyroidectomy. An Overview and Country Perspectives, Curr. Among exercise-induced hormones increased by maternal exercise, apelin was present at higher level in maternal and fetal circulation and at the level of the placenta. In recent years, studies are focusing on BAT as a possible therapeutic target. The Feature Paper can be either an original research article, a substantial novel research study that often involves ; Vicentini, T.M. Fetal Origins of Adult Disease. A sub-study of a randomized, double-blind, placebo-controlled study. Madsen, L.; Kristiansen, K. Of Mice and Men: Factors Abrogating the Antiobesity Effect of Omega-3 Fatty Acids. Xiang, A.S.; Giles, C.; Loh, R.K.C. ; Karagas, M.R. Hui, S.; Liu, Y.; Huang, L. Resveratrol Enhances Brown Adipose Tissue Activity and White Adipose Tissue Browning in Part by Regulating Bile Acid Metabolism via Gut Microbiota Remodeling. ; Jiang, Z.; Du, M. Maternal Exercise via Exerkine Apelin Enhances Brown Adipogenesis and Prevents Metabolic Dysfunction in Offspring Mice. This suggestion is consistent with the observation that cold exposure of old rats at 10C for five consecutive days significantly increases brown fat mass and BAT cell size. ; Kajimura, S. Relevance of Brown Adipose Tissue in Infancy and Adolescence. Finally, brown fat tissue norepinephrine release measured during cold exposure remains robust in old rats (Figure 6). ; Smyth, G.; Liew, C.W. Visit our dedicated information section to learn more about MDPI. Mueller, N.T. Changes in Parental Smoking during Pregnancy and Risks of Adverse Birth Outcomes and Childhood Overweight in Europe and North America: An Individual Participant Data Meta-Analysis of 229,000 Singleton Births. Kalupahana, N.S. Coscia, A.; Bardanzellu, F.; Caboni, E.; Fanos, V.; Peroni, D.G. Other publications came from the reference list of other papers, hand searches and from the personal reference databases of the authors. European Childhood Obesity Trial Study group. Law, J.M. Ferguson, J.F. Fish Oil Diet Modulates Epididymal and Inguinal Adipocyte Metabolism in Mice. Smaller amounts can be found in other adipose depots normally considered white, although their contribution to total heat production is rather minor. Previously, it was thought that brown fat disappears in humans after infancy. ; Hellgren, L.I. Brown adipose tissue (BAT) is not only abundantly found in rodents and in human infants, but also in human adults. Zhao, M.; Chen, X. Eicosapentaenoic Acid Promotes Thermogenic and Fatty Acid Storage Capacity in Mouse Subcutaneous Adipocytes. Reducing the number of cigarettes, without quitting, did not decrease this risk [. Symonds, M.E. Lipids, Help us to further improve by taking part in this short 5 minute survey, Measuring and Leveraging Motives and Values in Dietary Interventions, Mediterranean Diet and Lifestyle Habits during Pregnancy: Is There an Association with Small for Gestational Age Infants? Plagge, A.; Gordon, E.; Dean, W.; Boiani, R.; Cinti, S.; Peters, J.; Kelsey, G. The Imprinted Signaling Protein XLs Is Required for Postnatal Adaptation to Feeding. Follow Tech Insider on Facebook and Twitter. ; Chavez, T.A. Feature Papers represent the most advanced research with significant potential for high impact in the field. Negron, S.G.; Ercan-Sencicek, A.G.; Freed, J.; Walters, M.; Lin, Z. ; Geurts, L.; Van Hul, M.; Cani, P.D. ; Pasquale, L.R. ; Havekes, B. Yu, H.; Dilbaz, S.; Comann, J.; Hoang, A.C.; Diedrich, V.; Herwig, A.; Harauma, A.; Hoshi, Y.; Moriguchi, T.; Landgraf, K.; et al. Clinical studies are needed to dissect the early factors and their modulation to allow proper BAT development and functions and to prevent onset of childhood obesity. GVZ and SC are grateful to the FoundationRomeo andEnricaInvernizzi. ; et al. Wu, J.; Bostrm, P.; Sparks, L.M. Zanotti, S.; Stadmeyer, L.; Smerdel-Ramoya, A.; Durant, D.; Canalis, E. Misexpression of CCAAT/Enhancer Binding Protein Beta Causes Osteopenia. Well-developed neonates already possess active brown adipose tissue at birth, while less mature species develop brown adipose tissue upon the cold exposure that follows birth. Ponrartana, S.; Patil, S.; Aggabao, P.C. ; Brinton, J.T. ; Garofalo, C.; Moine, Q.; Desjardins, Y.; Levy, E.; et al. Quantification of Brown and White Adipose Tissue Based on Gaussian Mixture Model Using WaterFat and MRI in Adolescents. Xiao, X.; Bai, J.; Li, M.S. ; Homer, C.S. ; Dietz, W.H. Examples of important factors released are triiodothyronine (T3), fibroblast growth factor 21 (FGF21), interleukin-6 (IL-6), vascular-endothelial growth factor-A (VEGF-A), nitric oxide (NO) and bone morphogenetic protein (BMP) [, Another interesting aspect is the fact that the ability of active BAT to expend high amounts of energy has raised interest in stimulating thermogenesis therapeutically to treat metabolic diseases related to obesity and type 2 diabetes [. Specifically, an abundance of genus, AGKs therefore have a role in the maintenance and differentiation of BeAT during infancy. articles published under an open access Creative Common CC BY license, any part of the article may be reused without Thermogenic Mechanisms and Their Hormonal Regulation. ; Cinti, S.; et al. Identification of Inducible Brown Adipocyte Progenitors Residing in Skeletal Muscle and White Fat. Pediatric Adolesc. MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. Timing of Introduction of Complementary FoodsUnited States, 2016-2018. ; Burmeister, C.; Havstad, S.; Levin, A.M.; Lynch, S.V. Kadooka, Y.; Sato, M.; Imaizumi, K.; Ogawa, A.; Ikuyama, K.; Akai, Y.; Okano, M.; Kagoshima, M.; Tsuchida, T. Regulation of Abdominal Adiposity by Probiotics (Lactobacillus Gasseri SBT2055) in Adults with Obese Tendencies in a Randomized Controlled Trial. ; Bailey, M.; Kamp Dush, C.; Schoppe-Sullivan, S.; Christian, L.M. Cassidy-Bushrow, A.E. ; Garcia-Valds, L.; Florido, J.; Padilla, M.C. Recently, research has focused on the role of the brown adipose tissue (BAT) as a potential target of intervention. You are accessing a machine-readable page. Maternal Body Weight and Gestational Diabetes Differentially Influence Placental and Pregnancy Outcomes. ; Carnero-Montoro, E.; Hardiman, T.; Martin, T.C. Gliniak, C.M. ; Budge, H.; et al. Couet, C.; Delarue, J.; Ritz, P. Effect of Dietary Fish Oil on Body Fat Mass and Basal Fat Oxidation in Healthy Adults. Park, S.-S.; Lee, Y.-J. ; Nachbar, R.T.; Varin, T.V. A Nutritional Perspective on UCP1-Dependent Thermogenesis. Symonds, M.E. A Polyphenol-Rich Cranberry Extract Protects from Diet-Induced Obesity, Insulin Resistance and Intestinal Inflammation in Association with Increased Akkermansia Spp. Symonds, M.E. ; Connelly, P.W. Noumi, Y.; Kawamura, R.; Tabara, Y. Both Proliferation and Lipogenesis of Brown Adipocytes Contribute to Postnatal Brown Adipose Tissue Growth in Mice. Greenberg, A.S.; Obin, M.S. Rzehak, P.; Saffery, R.; Reischl, E.; Covic, M.; Wahl, S.; Grote, V.; Xhonneux, A.; Langhendries, J.-P.; Ferre, N.; Closa-Monasterolo, R.; et al. Luoto, R.; Kalliomki, M.; Laitinen, K.; Delzenne, N.M.; Cani, P.D. Although BAT endocrine function is poorly characterized, it has been recently described that BAT produces factors such as fibroblast growth factor 21 and retinol binding protein, which could modulate the function of other metabolic organs [21]. ; Lin, F.P. permission provided that the original article is clearly cited. The process can occur because of the presence in the mitochondrial inner membrane of the UCP1, which transports proton (equivalents) across the membrane to dissipate the proton gradient formed during substrate oxidation. Effects of docosahexanoic acid supplementation on inflammatory and subcutaneous adipose tissue gene expression in HIV-infected patients on combination antiretroviral therapy (cART). The statements, opinions and data contained in the journals are solely ; Morris, D.E. Mehul T. Dattani, Delbert A. Fisher, in Williams Textbook of Endocrinology (Twelfth Edition), 2011. Betz, M.J.; Enerbck, S. Human Brown Adipose Tissue: What We Have Learned So Far. ; Kahn, C.R. ; Souza, A.S.; Muros, M.F. Cell Biol. Impact of Cyanidin-3-Glucoside on Gut Microbiota and Relationship with Metabolism and Inflammation in High Fat-High Sucrose Diet-Induced Insulin Resistant Mice. These are represented by the nutritional status of the mother [, Docosahexaenoic acid (DHA, C22:6n-3) and eicosapentaenoic acid (EPA C20:5, Omega-3 (EPA and DHA) can potentially exert an effect on the well-known obesity phenotype, characterized by a chronic low-grade inflammation, in which PUFAs might mediate some metabolic and pro-inflammatory mechanisms [, Increasing evidence underlines that omega-3 PUFA might have a role on adipogenesis and lipid metabolism of WAT in animal models. Excessive gestational weight gain, in early and mid-pregnancy, has been associated with high birth weight and lower leptin levels in offspring, factors known to increase the risk of overweight later in life [, Interestingly, it has also been shown that infants of mothers with an adequate gestational weight gain not only have a lower fat mass, but also a more diverse microbiome with respect to babies born from mothers with excessive gestational weight gain [, The mechanisms responsible for this association have not been elucidated in humans yet.