Adipose tissue is a major metabolic organ, and it has been traditionally classified as either white adipose tissue(WAT) or brown adipose tissue(BAT). WAT and BAT are characterized by different anatomical locations, mo...Adipose tissue is a major metabolic organ, and it has been traditionally classified as either white adipose tissue(WAT) or brown adipose tissue(BAT). WAT and BAT are characterized by different anatomical locations, morphological structures, functions, and regulations. WAT and BAT are both involved in energy balance. WAT is mainly involved in the storage and mobilization of energy in the form of triglycerides, whereas BAT specializes in dissipating energy as heat during cold- or diet-induced thermogenesis. Recently, brownlike adipocytes were discovered in WAT. These brownlike adipocytes that appear in WAT are called beige or brite adipocytes. Interestingly, these beige/brite cells resemble white fat cells in the basal state, but they respond to thermogenic stimuli with increased levels of thermogenic genes and increased respiration rates. In addition, beige/brite cells have a gene expressionpattern distinct from that of either white or brown fat cells. The current epidemic of obesity has increased the interest in studying adipocyte formation(adipogenesis), especially in beige/brite cells. This review summarizes the developmental process of adipose tissues that originate from the mesenchymal stem cells and the features of these three different types of adipocytes.展开更多
Beige adipocytes are believed to have a high ability to consume fat. As such, compounds capable of inducing the development of beige adipocytes may be useful as drugs for anti-obesity and anti-type 2 diabetes. However...Beige adipocytes are believed to have a high ability to consume fat. As such, compounds capable of inducing the development of beige adipocytes may be useful as drugs for anti-obesity and anti-type 2 diabetes. However, the true nature of beige adipocytes remains unclear. The purpose of this study is to confirm whether or not white adipocyte can differentiate to beige adipocytes and to clarify the characteristics of beige adipocytes. We first searched for an inducer of beige adipocytes and found that kikyo extract, a component of bofu-tsusho-san, was a strong inducer. We then attempted to prove that beige adipocytes could be induced from white adipocytes. Second, we clarified the characteristics of beige adipocytes induced from white adipocytes. The results suggested that beige adipocytes were high-performance adipocytes with a greater ability to synthesize and consume triglyceride and take up glucose than white adipocytes.展开更多
最近的研究发现，与传统的白色和棕色脂肪细胞不同，脂肪组织中还存在另外一种新型的脂肪细胞，它们散在分布于白色脂肪组织中，受寒冷刺激或B，肾上腺素能受体激动剂激活后，表现出棕色脂肪细胞的特点，棕色脂肪细胞特异的解耦联蛋白1...最近的研究发现，与传统的白色和棕色脂肪细胞不同，脂肪组织中还存在另外一种新型的脂肪细胞，它们散在分布于白色脂肪组织中，受寒冷刺激或B，肾上腺素能受体激动剂激活后，表现出棕色脂肪细胞的特点，棕色脂肪细胞特异的解耦联蛋白1（UCPl）等基因的表达显著增高，产热和能量消耗能力增强。这一过程被称为“白色脂肪细胞棕色化”，这些细胞被命名为brite（brown to white）细胞或者beige （the intermediate color between white and brown）细胞。由于beige细胞在机体内分布广泛，并具有显著的消耗能量的功能，因此可能成为未来减肥药物开发的靶点。展开更多
Pigs lack functional uncoupling protein 1 （UCP1） making them susceptible to cold. Nevertheless, several pig breeds are known to be cold resistant. The molecular mechanism（s） enabling such adaptation are currently ...Pigs lack functional uncoupling protein 1 （UCP1） making them susceptible to cold. Nevertheless, several pig breeds are known to be cold resistant. The molecular mechanism（s） enabling such adaptation are currently unknown. Here, we show that this resist- ance is not dependent on shivering, but rather depends on UCP3 and white adipose tissue （WAT） browning. In two cold-resistant breeds （Tibetan and Min）, but not a cold-sensitive breed （Bama）, WAT browning was induced after cold exposure. Beige adipo- cytes from Tibetan pigs exhibited greater oxidative capacity than those from Bama pigs. Notably, UCP3 expression was signifi- cantly increased only in cold-resistant breeds, and knockdown of UCP3 expression in Tibetan adipocytes phenocopied Bama adipocytes in culture. Moreover, the eight dominant pig breeds found across China can be classified into cold-sensitive and cold- resistant breeds based on the UCP3 cDNA sequence. This study indicates that UCP3 has contributed to the evolution of cold resistance in the pig and overturns the orthodoxy that UCP1 is the only thermogenic uncoupling protein.展开更多
Sympathetic arborizations act as the essential efferent signals in regulating the metabolism of peripheral organs including white adipose tissues （WAT）. However, whether these local neural structures would be of pla...Sympathetic arborizations act as the essential efferent signals in regulating the metabolism of peripheral organs including white adipose tissues （WAT）. However, whether these local neural structures would be of plastic nature, and how such plasticity might participate in specific metabolic events of WAT, remains largely uncharacterized. In this study, we exploit the new vol- ume fluorescence-imaging technique to observe the significant, and also reversible, plasticity of intra-adi- pose sympathetic arborizations in mouse inguinal WAT in response to cold challenge. We demonstrate that this sympathetic plasticity depends on the cold-elicited sig- nal of nerve growth factor （NGF） and TrkA receptor. Blockage of NGF or TrkA signaling suppresses intra- adipose sympathetic plasticity, and moreover, the cold- induced beiging process of WAT. Furthermore, we show that NGF expression in WAT depends on the cate- cholamine signal in cold challenge. We therefore reveal the key physiological relevance, together with the reg- ulatory mechanism, of intra-adipose sympathetic plas- ticity in the WAT metabolism.展开更多
Adipose tissue is an important organ for energy homeostasis. White adipose tissue stores energy in the form of triglycerides, whereas brown adipocytes and recently identified beige adipocytes are specialized in dissip...Adipose tissue is an important organ for energy homeostasis. White adipose tissue stores energy in the form of triglycerides, whereas brown adipocytes and recently identified beige adipocytes are specialized in dissipating energy by thermogenesis or contribution to dispose glucose and clear triglycerides in blood. The inverse correlation between the brown adipose tissue activity and body mass suggests its protective role against body fat accumulation. Thus, recruitment and activation of brown or beige adipose tissue become particularly appealing targets for increasing energy expenditure. Angiogenesis and sympathetic nerve signals are the fundamental determinants for brown and beige adipose tissue development, as well as for their metabolic functions. Secretary factors including BMPs can induce the development, the activation of brown or beige adipose tissue, which seem to be promising for therapeutic development.展开更多
To the Editor:Obesity, an epidemic metabolic disease characterized by excessive fat accumulation, causes a significant economic burden on families and the society. The discovery of beige adipocytes has provided us wit...To the Editor:Obesity, an epidemic metabolic disease characterized by excessive fat accumulation, causes a significant economic burden on families and the society. The discovery of beige adipocytes has provided us with a brand new approach for the intervention of obesity^(1). Beige adipocytes increase energy expenditure and improve the balance of glucose and lipid metabolism. Reduction of beige adipocytes is a hallmark of obesity. Mechanism underlying the decrement of beigeing remains largely unknown.展开更多
Beige/brown adipocytes play a crucial role in regulating the body’s overall energy balance.The thermogenic function is under the influence of various tissues,including the brain,muscles,and liver.However,the breast t...Beige/brown adipocytes play a crucial role in regulating the body’s overall energy balance.The thermogenic function is under the influence of various tissues,including the brain,muscles,and liver.However,the breast tissue is not in the list.展开更多
Background Thermogenic adipose tissue,both beige and brown,experiences whitening as animals are exposed to warmth and age,but the potential mechanisms are not fully understood.In this study,we employed singlenucleus R...Background Thermogenic adipose tissue,both beige and brown,experiences whitening as animals are exposed to warmth and age,but the potential mechanisms are not fully understood.In this study,we employed singlenucleus RNA-seq to construct a cell atlas during whitening progression and identified the characteristics of thermogenic adipocytes.Results Our histological studies and bulk transcriptome gene expression analysis confirmed that both perirenal and omental adipose tissues(pAT and oAT)exhibited progressive whitening in goats.Compared to the classic brown adipocytes in mice,goat thermogenic adipocytes were more closely related in gene expression patterns to human beige adipocytes,which was also confirmed by adipocyte type-and lineage-specific marker expression analysis.Furthermore,trajectory analysis revealed beige-and white-like adipocytes deriving from a common origin,coexisting and undergoing the transdifferentiation.In addition,differences in gene expression profiles and cell communication patterns(e.g.,FGF and CALCR signaling)between oAT and pAT suggested a lower thermogenic capacity of oAT than that of pAT.Conclusions We constructed a cell atlas of goat pAT and oAT and descripted the characteristics of thermogenic adipocytes during whitening progression.Altogether,our results make a significant contribution to the molecular and cellular mechanisms behind the whitening of thermogenic adipocytes,and providing new insights into obesity prevention in humans and cold adaptation in animals.展开更多
基金Supported by Grants from the National Research of Foundation of the South Korea,No.2012M3A9C7050101,No.2011-0030028 and No.2006-2004112
文摘Adipose tissue is a major metabolic organ, and it has been traditionally classified as either white adipose tissue(WAT) or brown adipose tissue(BAT). WAT and BAT are characterized by different anatomical locations, morphological structures, functions, and regulations. WAT and BAT are both involved in energy balance. WAT is mainly involved in the storage and mobilization of energy in the form of triglycerides, whereas BAT specializes in dissipating energy as heat during cold- or diet-induced thermogenesis. Recently, brownlike adipocytes were discovered in WAT. These brownlike adipocytes that appear in WAT are called beige or brite adipocytes. Interestingly, these beige/brite cells resemble white fat cells in the basal state, but they respond to thermogenic stimuli with increased levels of thermogenic genes and increased respiration rates. In addition, beige/brite cells have a gene expressionpattern distinct from that of either white or brown fat cells. The current epidemic of obesity has increased the interest in studying adipocyte formation(adipogenesis), especially in beige/brite cells. This review summarizes the developmental process of adipose tissues that originate from the mesenchymal stem cells and the features of these three different types of adipocytes.
文摘Beige adipocytes are believed to have a high ability to consume fat. As such, compounds capable of inducing the development of beige adipocytes may be useful as drugs for anti-obesity and anti-type 2 diabetes. However, the true nature of beige adipocytes remains unclear. The purpose of this study is to confirm whether or not white adipocyte can differentiate to beige adipocytes and to clarify the characteristics of beige adipocytes. We first searched for an inducer of beige adipocytes and found that kikyo extract, a component of bofu-tsusho-san, was a strong inducer. We then attempted to prove that beige adipocytes could be induced from white adipocytes. Second, we clarified the characteristics of beige adipocytes induced from white adipocytes. The results suggested that beige adipocytes were high-performance adipocytes with a greater ability to synthesize and consume triglyceride and take up glucose than white adipocytes.
文摘最近的研究发现，与传统的白色和棕色脂肪细胞不同，脂肪组织中还存在另外一种新型的脂肪细胞，它们散在分布于白色脂肪组织中，受寒冷刺激或B，肾上腺素能受体激动剂激活后，表现出棕色脂肪细胞的特点，棕色脂肪细胞特异的解耦联蛋白1（UCPl）等基因的表达显著增高，产热和能量消耗能力增强。这一过程被称为“白色脂肪细胞棕色化”，这些细胞被命名为brite（brown to white）细胞或者beige （the intermediate color between white and brown）细胞。由于beige细胞在机体内分布广泛，并具有显著的消耗能量的功能，因此可能成为未来减肥药物开发的靶点。
文摘Pigs lack functional uncoupling protein 1 （UCP1） making them susceptible to cold. Nevertheless, several pig breeds are known to be cold resistant. The molecular mechanism（s） enabling such adaptation are currently unknown. Here, we show that this resist- ance is not dependent on shivering, but rather depends on UCP3 and white adipose tissue （WAT） browning. In two cold-resistant breeds （Tibetan and Min）, but not a cold-sensitive breed （Bama）, WAT browning was induced after cold exposure. Beige adipo- cytes from Tibetan pigs exhibited greater oxidative capacity than those from Bama pigs. Notably, UCP3 expression was signifi- cantly increased only in cold-resistant breeds, and knockdown of UCP3 expression in Tibetan adipocytes phenocopied Bama adipocytes in culture. Moreover, the eight dominant pig breeds found across China can be classified into cold-sensitive and cold- resistant breeds based on the UCP3 cDNA sequence. This study indicates that UCP3 has contributed to the evolution of cold resistance in the pig and overturns the orthodoxy that UCP1 is the only thermogenic uncoupling protein.
基金We thank members of the Zeng laboratory for helps and discussions. This work was supported by National Natural Science Foun- dation of China （Grant Nos. 31770936 and 91742106） to Wenwen Zeng, Beijing Natural Science Foundation （5172016） to Wenwen Zeng, Thousand-Talent Young Investigator Program to Wenwen Zeng, and National Key R＆D Program of China （2017YFA0505800）. The Zeng laboratory was also supported by Center for Life Sciences, Institute for Immunology, and School of Medicine at Tsinghua University.
文摘Sympathetic arborizations act as the essential efferent signals in regulating the metabolism of peripheral organs including white adipose tissues （WAT）. However, whether these local neural structures would be of plastic nature, and how such plasticity might participate in specific metabolic events of WAT, remains largely uncharacterized. In this study, we exploit the new vol- ume fluorescence-imaging technique to observe the significant, and also reversible, plasticity of intra-adi- pose sympathetic arborizations in mouse inguinal WAT in response to cold challenge. We demonstrate that this sympathetic plasticity depends on the cold-elicited sig- nal of nerve growth factor （NGF） and TrkA receptor. Blockage of NGF or TrkA signaling suppresses intra- adipose sympathetic plasticity, and moreover, the cold- induced beiging process of WAT. Furthermore, we show that NGF expression in WAT depends on the cate- cholamine signal in cold challenge. We therefore reveal the key physiological relevance, together with the reg- ulatory mechanism, of intra-adipose sympathetic plas- ticity in the WAT metabolism.
文摘Adipose tissue is an important organ for energy homeostasis. White adipose tissue stores energy in the form of triglycerides, whereas brown adipocytes and recently identified beige adipocytes are specialized in dissipating energy by thermogenesis or contribution to dispose glucose and clear triglycerides in blood. The inverse correlation between the brown adipose tissue activity and body mass suggests its protective role against body fat accumulation. Thus, recruitment and activation of brown or beige adipose tissue become particularly appealing targets for increasing energy expenditure. Angiogenesis and sympathetic nerve signals are the fundamental determinants for brown and beige adipose tissue development, as well as for their metabolic functions. Secretary factors including BMPs can induce the development, the activation of brown or beige adipose tissue, which seem to be promising for therapeutic development.
基金supported by grants from the National Natural Science Foundation of China(81730020,81930015,and 82070592)National Institutes of Health Grant R01D K112755,1R01DK129360 and 1R01DK110273(USA)。
文摘To the Editor:Obesity, an epidemic metabolic disease characterized by excessive fat accumulation, causes a significant economic burden on families and the society. The discovery of beige adipocytes has provided us with a brand new approach for the intervention of obesity^(1). Beige adipocytes increase energy expenditure and improve the balance of glucose and lipid metabolism. Reduction of beige adipocytes is a hallmark of obesity. Mechanism underlying the decrement of beigeing remains largely unknown.
基金supported by a project(32271220)from the National Natural Science Foundation of China to Jianping Ye。
文摘Beige/brown adipocytes play a crucial role in regulating the body’s overall energy balance.The thermogenic function is under the influence of various tissues,including the brain,muscles,and liver.However,the breast tissue is not in the list.
基金supported by the National Key Research and Development Programme of China(grant number 2021YFF1001000)the National Natural Science Foundation of China(grant number 32170627)+1 种基金the Postdoctoral Innovative Talents Support Program of China(grant number BX20200282)the Natural Science Foundation of Sichuan Province(grant number 23NSFSC1804).
文摘Background Thermogenic adipose tissue,both beige and brown,experiences whitening as animals are exposed to warmth and age,but the potential mechanisms are not fully understood.In this study,we employed singlenucleus RNA-seq to construct a cell atlas during whitening progression and identified the characteristics of thermogenic adipocytes.Results Our histological studies and bulk transcriptome gene expression analysis confirmed that both perirenal and omental adipose tissues(pAT and oAT)exhibited progressive whitening in goats.Compared to the classic brown adipocytes in mice,goat thermogenic adipocytes were more closely related in gene expression patterns to human beige adipocytes,which was also confirmed by adipocyte type-and lineage-specific marker expression analysis.Furthermore,trajectory analysis revealed beige-and white-like adipocytes deriving from a common origin,coexisting and undergoing the transdifferentiation.In addition,differences in gene expression profiles and cell communication patterns(e.g.,FGF and CALCR signaling)between oAT and pAT suggested a lower thermogenic capacity of oAT than that of pAT.Conclusions We constructed a cell atlas of goat pAT and oAT and descripted the characteristics of thermogenic adipocytes during whitening progression.Altogether,our results make a significant contribution to the molecular and cellular mechanisms behind the whitening of thermogenic adipocytes,and providing new insights into obesity prevention in humans and cold adaptation in animals.
