Obesity copyright 2019 the gut microbiota regulates. Proceedings of the society for experimental biology and medicine. Ronald kahna,1 asection of integrative physiology and metabolism, research division, joslin diabetes center, harvard medical school, boston, ma 02215. The role of brown adipose tissue in dietinduced thermogenesis volume 48 issue 2 michael j. Not all white adipose tissue is prone to acquire beige adipocytes. In rodents, bat thermogenesis also contributes to the febrile increase in core temperature during the immune response. Brown fat fuel utilization and thermogenesis kristy l. Brown adipose tissue thermogenesis and the energetics of pregnancy and lactation in rodents. Glucocorticoids modulate human brown adipose tissue. Comprehensive amelioration of highfat dietinduced metabolic.
Wat is the primary site of energy storage and of release of hormones and cytokines that modulate wholebody metabolism and insulin resistance 1215. Autonomic regulation of brown adipose tissue thermogenesis in. Bat was previously considered to have no physiologic relevance in adult. Another type of adipose tissue, the brown adipose tissue bat, is in charge of utilizing nutrients to produce heat in an attempt to maintain body temperature through nonshivering adaptive thermogenesis. Adenoviral delivery of cre recombinase significantly reduced gatm transcript levels in primary brown adipocytes from gatm floxflox flox animals, relative to gfp virus figure 1b. Programming mediated by fatty acids affects uncoupling. Brown adipose tissue and batokines brown adipose tissue bat activity has a protective role against chronic metabolic disease such as obesity or diabetes which have been attributed to its capacity of using glucose and fat for thermogenesis. One of the first works published in 1988 showed that 48 h. Coldinduced thermogenesis is an important component of total energy expenditure and contributes to overall energy balance. Inflammation of brown beige adipose tissues in obesity and. Both white adipose tissue wat and brown adipose tissue bat make up the adipose organ. Celi abstract brown adipose tissue bat, brown inwhite brite and beige adipocytes share the unique ability of converting chemical energy into heat and play a critical role in the adaptive thermogenesis response promoting nonshivering ther. To examine the physiological relevance of adipose tissue creatine metabolism, we deleted the ratelimiting enzyme of creatine biosynthesis selectively in adipose tissue figure 1a. Pdf myristoleic acid produced by enterococci reduces.
The physiological basis for the enormous capacity of bat for heat production during cold exposure awaited the ingenious application of radiolabeled microspheres to measure blood flow in. B poa is considered to be a major coordinator of thermoregulation as it receives inputs from thermoreceptors essentially located in the skin. Brown adipose tissue bat undergoes rapid postnatal development and then protects against cold and obesity into adulthood. Adipose tissue can be classified into two subtypes.
Nonadrenergic control of lipolysis and thermogenesis in. Brown adipose tissue and thermogenesis depends on the composition of the various types of adipo cytes, classified as white, beig e or brown table 1. Cold but not sympathomimetics activates human brown. Frontiers hypothalamic control of brown adipose tissue. Regulation of brown adipose tissue thermogenesis by dietary fatty acids. Microbiota depletion impairs thermogenesis of brown. Stock skip to main content we use cookies to distinguish you from other users and to provide you with a better experience on our websites. White adipose functions as an energy storage depot characterized by large lipid droplets and is a prominent endocrine organ that produces hormones to regulate feeding and satiety 5, 6. Perhaps its a good time to use the technical terms of adipose tissue instead of fat cells as well as lipids instead of fats. Using fluorodeoxyglucosepositron emission tomography and computed tomography, we previously reported that bat decreases with age and thereby accelerates agerelated accumulation of body fat in humans. The function ascribed to brown adipose tissue in humans has long been confined to thermoregulation in neonates, where this thermogenic capacity was thought lost with maturation.
Brown adipose tissue thermogenesis in humans springerlink. Brown adipose tissue derived angptl4 controls glucose and. Recent observation of brown adipose tissue bat being functional in adult humans provides a rationale for its stimulation to increase energy expenditure through adaptive thermogenesis for an antiobesity strategy. Brown adipose tissue bat is the main site of nonshivering thermogenesis and is therefore a relevant site for adaptive energy expenditure processes. It also is related to nonshivering thermogenesis and en docrine control of metabolism, that is directly associated to the pathophysiology of distinct fat depots. Targeting thermogenesis in brown fat and muscle to treat.
Brown adipose tissue has high metabolic activity and is responsible for thermogenesis. Brown adipose tissue ucp1mediated thermogenesis is activated by fatty acids produced via norepinephrineinduced intracellular. Jul 15, 20 embryonic development of brown adipose tissue. A major tissue responsible for nst is brown adipose tissue bat.
Brown adipose tissue thermogenic capacity is regulated by elovl6. Schulz1 and yuhua tseng2,3, 1research group adipocyte development, german institute of human nutrition, nuthetal, germany 2integrative physiology and metabolism, joslin diabetes center, harvard medical school, boston, ma, usa. Brown adipose tissue bat is a thermogenic organ that is involved in energy expenditure and represents an attractive target to combat both obesity and type 2 diabetes. Brown adipose tissue has been found in newborns and is involved in nonshivering thermogenesis. Brown adipose tissue activation is linked to distinct. Aug 16, 2015 brown adipose tissue is more closely related to muscle tissue than it is to white adipose tissue bat has many lipid droplets compared to the single lipidfilled space of wat image. The real significance of brown adipose tissue depots in human metabolism, as seen, is still highly speculative. The major form of adipose tissue in mammals commonly referred to as fat is white adipose tissue, wat. Production of heat in bat is mediated by betaadrenergic signaling and subsequent uncoupling. Like coldinduced thermogenesis, this form of heat production involves changes in the activity of the sym pathetic nervous system and brown adipose tissue which suggest that this tissue may determine metabolic effi. However, the molecular mechanism that determines postnatal development. Evidence for two types of brown adipose tissue in humans.
Brown adipose tissue is well known to be a thermoregulatory organ particularly important in small rodents and human infants, but it was only recently that its existence and significance to metabolic fitness in adult humans have been widely realized. Bat thermogenesis is stimulated by cold exposure through. A schematic and tentative representation of the hypothalamic structures involved in the control of bat thermogenesis. Brown adipose tissue bat, in contrast to bona fide white fat, can dissipate significant amounts of chemical energy through uncoupled respiration and heat production thermogenesis. Due to its unique metabolic function, brown adipose tissue bat has recently been in the focus of metabolism research. Brown adipose tissue bat has been known to be the effector organ for. This process is mediated by the major thermogenic factor uncoupling protein1 and can be activated by certain stimuli, such as cold exposure, adrenergic compounds. The concept that brown adipose tissue bat is a thermogenic tissue initially came from morphological changes in the tissue when animals were exposed to the cold smith and horwitz, 1969. Specialized adipose tissue that is primarily tasked with thermogenesis, especially in the neonate, is brown adipose tissue, bat. Bat is abundant in mammals with high thermoregulatory demands, such as small mammals and the neonates of large mammals 1.
In recent years, the topic of brown adipose tissue has been reinvigo. In humans, bat is present in newborns, but disappears rapidly during postnatal periods and, in adults, is. Brown adipose tissue bat takes up and burns fatty acids for thermogenesis in mice. Qki regulates adipose tissue metabolism by acting as a.
Oct 23, 2017 coldinduced thermogenesis is an important component of total energy expenditure and contributes to overall energy balance. Although brown fat was once considered only necessary in babies, recent morphological and imaging studies have provided evidence that, contrary to prior belief, this tissue is present and active in adult humans. Brown adipose tissue oxidative metabolism contributes to. Lipolysis in brown adipocytes is not essential for cold. In humans, gtf2ird1 expression inversely correlates with subcutaneous wat. Brown adipose tissue thermogenesis and the energetics of. Brown adipose tissue is the major site for newborn thermogenesis. Mature brown adipocytes contain abundant mitochondria and express high levels of uncoupling protein 1 ucp1, which dissipates the proton gradient across the mitochondrial inner membrane to produce heat. Jci cold acclimation recruits human brown fat and increases. Brown adipose tissue bat defends against hypothermia in small mammals and newborn infants through thermogenesis. Brown adipose tissue bat burns fat to produce heat when the body is exposed to cold and plays a role in energy metabolism. The brown adipose tissue bat evolved as a specialized thermogenic organ in mammals.
Subcutaneous depots such as the inguinal wat iwat recruit beige adipocytes in response to longterm cold exposure or after stimulation by. Brown adipose tissue bat is vital for proper thermogenesis during cold exposure in rodents, but until recently its presence in adult humans and its contribution to human metabolism were thought to be minimal or insignificant. Cypessa, yihchieh chenb, cathy szea, ke wangb, jeffrey englishb, onyee chana, ashley r. Repression of adipose tissue fibrosis through a prdm16. Nonshivering thermogenesis in brown adipose tissue bat plays a central role in energy homeostasis. Nrf1mediated proteosome activity in brown fat is required for the normal thermogenic behavior of this tissue in mice. The concept that some individuals have a greater ability to increase energy expenditure ee in response to overeating has been appealing since dietinduced thermogenesis dit was linked to the activation of brown adipose tissue bat in rats. Qki regulates adipose tissue metabolism by acting as a brake. Flavonoids as inducers of white adipose tissue browning.
If the inline pdf is not rendering correctly, you can download the pdf file here. Thioesterase superfamily member 1 them1, a batenriched long chain fatty acylcoa thioesterase, is upregulated by cold and downregulated by warm ambient temperatures. Does adipose tissue thermogenesis play a role in metabolic. Bat is socalled because it is darkly pigmented due to the high density of mitochondria rich in cytochromes. Glucocorticoids modulate human brown adipose tissue thermogenesis in vivo hannah scotneya, michael e. Society for experimental biology and medicine 208, 159169. The physiological basis for the enormous capacity of bat for heat production during cold exposure awaited the ingenious application of radiolabeled microspheres to measure blood flow in bat and. Genetic depletion of adipocyte creatine metabolism. Intracellular fatty acids are stored in the format of triglyceride in the h. However, the potential impact of gut microbiota on the thermogenic process is confused. In contrast to wat, brown adipose tissue bat plays an important role in energy metabolism via generating heat by an adaptive process called nonshivering thermogenesis, which requires fuel fatty acid and glucose and uncoupling protein 1 ucp1. Jan 11, 2012 we therefore analysed the adipose tissue of the pgc1. Mettl3 is essential for postnatal development of brown. Nonadrenergic control of lipolysis and thermogenesis in adipose tissues katharina braun 1,2,3, josef oeckl.
Brown adipose tissue bat dissipates energy as heat to maintain optimal thermogenesis and to contribute to energy expenditure, in rodents and possibly humans. Brown adipose tissue energy metabolism in humans request pdf. Brown adipose tissue thermogenesis and the energetics of pregnancy and lactation in rodents paul trayhurn and denis richard dutiti nutrition laboratory, medical research council and university of canibridge, downhatn s lane, milton road, cambridge cb4 ixj, u. Cold exposure and exercise training are two stimuli that have been investigated with respect to bat activation, metabolism, and the contribution of bat to metabolic health. Adipose tissue can be broadly divided into two types, brown adipose tissue bat and white adipose tissue wat.
Conversely, bat is a tissue designed for maintaining body temperature significantly higher than ambient temperatures through heat. The previously observed supraclavicular depot of brown adipose tissue bat in adult humans was commonly believed to be the equivalent of the. Thyroid hormones significantly influence energy expenditure by affecting the activity of metabolic active tissues, among which, mammalian brown adipose tissue bat plays a significant role. Frequent extreme cold exposure and brown fat and coldinduced thermogenesis. Brown adipose tissue bat plays an important role in metabolism and energy expenditure 1, and its most distinct features include a large number of mitochondria, abundant expression of uncoupling protein1 ucp1, and numerous small oil droplets in a single cell 1, 2. Here, we evaluated how bat and white adipose tissue wat responded to temperature challenges in mice lacking gut microbiota. Here we aimed to explore the role of cdk7 in thermogenic fat. Whereas white adipose tissue wat stores energy in the form of triglycerides and releases free fatty acids on demand, brown adipose tissue bat burns fat to maintain the temperature in a process called nonshivering thermogenesis. Frequent extreme cold exposure and brown fat and coldinduced. Brown adipose tissue bat and beige adipocytes facilitate thermogenesis to maintain host core body temperature during cold exposure. Despite the presence of ucp1 orthologues prior to the. Besides their endocrine functions, bat and wat mainly function to dissipate and store energy, respectively, in response to environmental and nutritional fluctuations. A two by two experimental study has been designed to determine the effect of gut microbiota on energy metabolism in mouse models.
Hormonal signaling factors produced by brown adipose tissue as. Many endocrine dysfunctions are associated with changes in metabolic rate that over time may result in changes in body weight. Bat was previously believed to be present only in small mammals and. During hibernation, its metabolism presents under hypothermia and it must achieve. Elongase, elovl6, brown adipose tissue, adaptive thermogenesis, fatty acid acyl chain length, energy expenditure sponsorship we thank the bbsrc, mrc, eu fp7 5 betabat and wellcome trust for funding this work. Pdf brown adipose tissue energy metabolism researchgate. For nst, energy metabolism of bat mitochondria is increased by activation of uncoupling protein 1 ucp1, which dissipates the proton motive force as heat. Overfeeding over 24 hours does not activate brown adipose. Brown adipose tissue is metabolically active, however, consuming fat and glucose, increasing metabolism, and generating warmth for the organism as needed. Coumaric acid prevents obesity via activating thermogenesis. Aug 10, 20 brown adipose tissue bat was first detected in small mammals and infants and defined as an adaptation to defend against the cold and to maintain body temperature many researchers over the decades have thought that brown adipose tissue is also important in adult humans. Recently, brown adipose tissue depots have been identified in adult humans.
Gut microbiota modulate the metabolism of brown adipose. The brown adipose tissue b at ev olved as a specialize d thermogenic organ in mammals. A genomic location of the three mir181 clusters mir181a1b1mir181a2b2, and mir181cd in mice. Role of brown adipose tissue thermogenesis in control of thermoregulatory feeding in rats. Thyroid hormone induces browning of white fat, but it is unclear whether this contributes to thermogenesis. Brown adipose tissue metabolism and thermogenesis annual. Adipose tissue metabolism can be induced in rodents through agonism of the fatspecific. There has been considerable recent interest in the concept.
Brown adipose tissue transplantation improves wholebody. We found that cdk7 brown adipose tissue batspecific knockout mice cdk7 bko have decreased bat mass, impaired. In addition to the energystoring white adipose tissue wat, mammals possess brown adipose tissue bat that burns fat to release heat for thermogenesis. Cyclindependent kinases cdks are emerging regulators of adipose tissue metabolism. Animals without the ability to shiver or tie scarves around their necks like rodents and newborns have lots of brown fat, because thats how they stay warm through non. Hypothalamic control of brown adipose tissue thermogenesis. Stressinduced activation of brown adipose tissue prevents obesity. Frequent extreme cold exposure and brown fat and cold. Despite decades of research, only recently have mechanistic studies started to. Brown fat and the myth of dietinduced thermogenesis. It occurs in all warmblooded animals, and also in a few species of thermogenic plants such as the eastern skunk cabbage, the voodoo lily, and the giant water lilies of the genus victoria.
Hormonal and environmental manipulation francesco s. The excess of energy is preferentially stored in white adipose tissue wat within unilocular adipocytes. The new color code of fat and its pharmacological implications alexander pfeifer and linda s. Cdk7 mediates the betaadrenergic signaling in thermogenic. Since the 1970s, brown adipose tissue bat has been increasingly recognized as the main site of nonshivering thermogenesis in mammals, and there are indications, as well as some debate, that it is also the site of the process called dietinduced thermogenesis. Brown adipose tissue is highly vascularised and innervated by the sympathetic nervous system, and its response varies depending on the nature of the external stimulus, such as age, sex, genetics and also diet 33. Saraf,1,8 palam annamalai,9 christina yfanti, 1,6 tony chao, 2 3 daniel wong,10 kosaku shinoda,10 sebastien m. Brown adipose tissue bat has long been recognized as the major site of nonshivering thermogenesis nst during cold exposure coldinduced thermogenesis cit and arousal from hibernation in. The energetic processes executed by bat require a readily available fuel supply, which includes glucose and fatty acids fas. However, analogously to what was discovered for white adipose tissue years ago.
Townsend1 and yuhua tseng1,2 1 joslin 2 diabetes center and harvard medical school, one place, boston, ma 02215, usa harvard stem cell institute, harvard university, cambridge, ma, usa brown adipose tissue bat dissipates energy as heat to maintain optimal thermogenesis and to contribute. Brown adipose tissue bat is a thermogenic organ that dissipates nutrient energy as heat, protecting animals from hypothermia and. Dec 23, 2019 mammalian adipose tissues are broadly classified as white adipose tissue wat, brown adipose tissue bat, and beige adipose tissue 3, 4. Thermogenesis is the process of heat production in organisms.
The demonstration of metabolically active brown adipose tissue bat in humans primarily using positron emission tomography coupled to computed tomography petct with the glucose tracer 18fluorodeoxyglucose 18fdg has renewed the interest of the scientific and medical community in the possible role of bat as a target for the prevention and treatment of obesity and type 2 diabetes t2d. Loss of tle3 promotes the mitochondrial program in beige. Thyroidhormoneinduced browning of white adipose tissue does. There has been considerable recent interest in the concept that thermogenesis in brown adipose tissue bat may play an important role in the regulation of energy balance, in. The mir181 family is a critical regulator of adipose tissue function. The significant oxidative capacity of brown adipocytes and the ability of their mitochondria to respire independently of atp production, has. The primary function of brown fat is to transform energy into. The metabolic phenotype of germfree gf, n 20 and conventional n 20 mice was characterized using a nmr spectroscopybased metabolic profiling approach, with a focus on sexual dimorphism 20 males, 20 females and energy metabolism in urine, plasma, liver.
Brown adipose tissue an overview sciencedirect topics. Instead, atgl in white adipose tissue and the heart is essential for supplying fatty acids during fasting and for meeting increased demands on the cardiovascular system in the cold, respectively. Brown adipose tissue energy metabolism in humans ncbi. From mouse to man, brown adipose tissue bat is a signi. It is generally accepted that adipocytes, both brown and white, arise from progenitor cells of the embryonic mesoderm, the only exception being the minor fat depots of the skull, which arise from stem cells of the ectodermal neural crest. For a long time, the modulation of bat activity by 3,3. Dietary fatty acid metabolism of brown adipose tissue in. Here we show that brown adipose tissue bat thermogenic function requires an adaptive increase in proteasomal activity to secure cellular protein quality control, and we identify the erlocalized. Bat produces heat via uncoupling protein1 ucp1, which uncouples the respiratory chain from atp production thereby releasing energy as heat. Pdf abstract the growing understanding of adipose tissue as an important endocrine organ with multiple metabolic functions has directed the attention. Although numerous studies have demonstrated the ability of phytochemical phenolic acids to improve obesity by activating bat, the underlying mechanism or mechanism therein remain obscure. May, 2015 in modern eutherian placental mammals, brown adipose tissue bat evolved as a specialized thermogenic organ that is responsible for adaptive nonshivering thermogenesis nst.
Mammalian adipose tissues are broadly classified as white adipose tissue wat, brown adipose tissue bat, and beige adipose tissue 3, 4. Frontiers brown adipose tissue energy metabolism in. Bat, different from wat which stores extra energy as tgs, dissipates chemical energy as heat via high levels of uncoupling protein 1 ucp1 and combats hypothermia and obesity by. Brown adipose tissue bat, a thermogenic organ likely to play a major role in. Dietary fatty acid metabolism of brown adipose tissue. Cold but not sympathomimetics activates human brown adipose tissue in vivo aaron m. In contrast, brown adipocytes are multilocular, contain substantial numbers of mitochondria and have high expression uncoupling protein 1 ucp1. Adrenergic responsiveness can be masked at subthermoneutral temperatures when thermoregulatory thermogenesis is active. Brown adipocytes are highly enriched in mitochondria. Brown adipose tissue bat has long been recognized as an energyconsuming organ and a possible target for combating metabolism disorder.
345 82 392 55 699 348 62 314 1231 257 263 961 594 464 744 1651 222 1571 1213 561 1271 237 734 652 16 505 638 660 1288 870 186 308 1405 148