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
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
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
目的:研究β3肾上腺素能受体激动剂CL316,243在体诱导小鼠各部位脂肪组织棕色化的时效性,明确其潜在的分子调控机制。方法:以10周龄C57BL/6J小鼠为研究对象,实验组分别腹腔注射CL316,243(1μg/g)1,3及5 d,对照组注射无菌生理盐水溶剂。...目的:研究β3肾上腺素能受体激动剂CL316,243在体诱导小鼠各部位脂肪组织棕色化的时效性,明确其潜在的分子调控机制。方法:以10周龄C57BL/6J小鼠为研究对象,实验组分别腹腔注射CL316,243(1μg/g)1,3及5 d,对照组注射无菌生理盐水溶剂。通过免疫组织化学法和基因表达分析等,观察不同作用时间下小鼠各部位脂肪组织的棕色化改变及产热相关基因及蛋白质的表达水平。结果:与对照组相比,在腹腔注射CL316,243第1天时附睾周围白色脂肪组织(epididymal white adipose tissue,eWAT)的重量就明显减轻,并且随着给药时间的延长,腹股沟皮下白色脂肪组织(inguinal subcutaneous white adipose tissue,sWAT)和eWAT中解偶联蛋白UCP-1 mRNA和蛋白质表达升高;而持续注射5 d能显著抑制小鼠的摄食及体重增加,并诱导小鼠肩胛部棕色脂肪(interscapular brown adipose tissue,iBAT)、sWAT及eWAT中细胞直径的缩小及小脂滴的聚集。结论:β3肾上腺素能受体激动剂CL316,243能在体诱导小鼠脂肪组织的棕色化,并且在不同脂肪组织中表现出不同的时效性特点。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
There are three types of fat tissue in mammals:white fat tissue(WAT),classic brown fat tissue(cBAT),and inducible brown fat tissue(iBAT)or beige fat tissue.The brown fat tissue in the human body is more similar to the...There are three types of fat tissue in mammals:white fat tissue(WAT),classic brown fat tissue(cBAT),and inducible brown fat tissue(iBAT)or beige fat tissue.The brown fat tissue in the human body is more similar to the induced brown fat tissue in mice.The main function of WAT is to store energy in the form of triacylglycerols and to regulate endocrine function.The main function of cBAT and iBAT is to generate heat and maintain the energy balance of the body.A cold environment and exercise can stimulate the browning of white fat tissue.The browning of white fat tissue is a complex process involving many factors,with PRDM16,PPARγand PGC-1αbeing the core transcription factors related to the process.Previous studies showed that white adipose browning is beneficial for the treatment of obesity,diabetes,fatty liver and other diseases.On the other hand,it can promote the progression of malignant tumors.Under normal conditions,the different types of fat tissue maintain a dynamic balance in the human body.Therefore,obtaining a better understanding of this balance and determining how to intervene at the early stages of metabolic imbalance are necessary.展开更多
Skeletal muscle plays a significant role in both local and systemic energy metabolism.The current investigation aims to explore the role of the Bambi gene in skeletal muscle,focusing on its implications for muscle hyp...Skeletal muscle plays a significant role in both local and systemic energy metabolism.The current investigation aims to explore the role of the Bambi gene in skeletal muscle,focusing on its implications for muscle hypertrophy and systemic metabolism.We hypothesize that skeletal muscle-specific deletion of Bambi induces muscle hypertrophy,improves metabolic performance,and activates thermogenic adipocytes via the reprogramming of progenitor of iWAT,offering potential therapeutic strategies for metabolic syndromes.Leveraging the Chromatin immunoprecipitation(ChIP)-seq and bioinformatics analysis,Bambi gene is shown to be a direct target of HIF2α,which is further confirmed by ChIP-qPCR and promoter luciferase assay.Skeletal muscle-specific Bambi deletion led to significant muscle hypertrophy and improved metabolic parameters,even under high-fat diet conditions.This deletion induced metabolic reprogramming of stromal vascular fractions(SVFs)into thermogenic adipocytes,contributing to systemic metabolic improvements,potentially through the secretory factor.Notably,mice with skeletal muscle-specific Bambi deletion demonstrate resistance to high-fat diet-induced metabolic disorders,highlighting a potential therapeutic pathway for metabolic syndrome management.Thus,skeletal muscle-specific deletion of Bambi triggers muscle growth,enhances metabolic performance,and activates thermogenic adipocytes.These findings suggest Bambi as a novel therapeutic target for metabolic syndromes,providing new insights into the interaction between muscle hypertrophy and systemic metabolic improvement.The study underscores the potential of manipulating muscle physiology to regulate whole-body metabolism,offering a novel perspective on treating metabolic disorders.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
Increasing brown and beige fat thermogenesis have an anti-obesity effect and thus great metabolic benefits.However,the molecular mechanisms regulating brown and beige fat thermogenesis remain to be further elucidated....Increasing brown and beige fat thermogenesis have an anti-obesity effect and thus great metabolic benefits.However,the molecular mechanisms regulating brown and beige fat thermogenesis remain to be further elucidated.We recently found that fat-specific knockout of Rheb promoted beige fat thermogenesis.In the current study,we show that Rheb has distinct effects on thermogenic gene expression in brown and beige fat.Fat-specific knockout of Rheb decreased protein kinase A(PKA)activity and thermogenic gene expression in brown adipose tissue of high-fat diet-fed mice.On the other hand,overexpression of Rheb activated PKA and increased uncoupling protein 1 expression in brown adipocytes.Mechanistically,Rheb overexpression in brown adipocytes increased Notch expression,leading to disassociation of the regulatory subunit from the catalytic subunit of PKA and subsequent PKA activation.Our study demonstrates that Rheb,by selectively modulating thermogenic gene expression in brown and beige adipose tissues,plays an important role in regulating energy homeostasis.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
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.
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.
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.
文摘目的:研究β3肾上腺素能受体激动剂CL316,243在体诱导小鼠各部位脂肪组织棕色化的时效性,明确其潜在的分子调控机制。方法:以10周龄C57BL/6J小鼠为研究对象,实验组分别腹腔注射CL316,243(1μg/g)1,3及5 d,对照组注射无菌生理盐水溶剂。通过免疫组织化学法和基因表达分析等,观察不同作用时间下小鼠各部位脂肪组织的棕色化改变及产热相关基因及蛋白质的表达水平。结果:与对照组相比,在腹腔注射CL316,243第1天时附睾周围白色脂肪组织(epididymal white adipose tissue,eWAT)的重量就明显减轻,并且随着给药时间的延长,腹股沟皮下白色脂肪组织(inguinal subcutaneous white adipose tissue,sWAT)和eWAT中解偶联蛋白UCP-1 mRNA和蛋白质表达升高;而持续注射5 d能显著抑制小鼠的摄食及体重增加,并诱导小鼠肩胛部棕色脂肪(interscapular brown adipose tissue,iBAT)、sWAT及eWAT中细胞直径的缩小及小脂滴的聚集。结论:β3肾上腺素能受体激动剂CL316,243能在体诱导小鼠脂肪组织的棕色化,并且在不同脂肪组织中表现出不同的时效性特点。
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.
基金the Zhejiang Provincial Nature Science Foundation of China,Y19C200025.
文摘There are three types of fat tissue in mammals:white fat tissue(WAT),classic brown fat tissue(cBAT),and inducible brown fat tissue(iBAT)or beige fat tissue.The brown fat tissue in the human body is more similar to the induced brown fat tissue in mice.The main function of WAT is to store energy in the form of triacylglycerols and to regulate endocrine function.The main function of cBAT and iBAT is to generate heat and maintain the energy balance of the body.A cold environment and exercise can stimulate the browning of white fat tissue.The browning of white fat tissue is a complex process involving many factors,with PRDM16,PPARγand PGC-1αbeing the core transcription factors related to the process.Previous studies showed that white adipose browning is beneficial for the treatment of obesity,diabetes,fatty liver and other diseases.On the other hand,it can promote the progression of malignant tumors.Under normal conditions,the different types of fat tissue maintain a dynamic balance in the human body.Therefore,obtaining a better understanding of this balance and determining how to intervene at the early stages of metabolic imbalance are necessary.
基金supported by National Natural Science Foundation of China(82072436)Guangdong Basic and Applied Basic Research Foundation(2020B1515020046)‘GDAS’Project of Science and Technology Development(2021GDASYL-20210102003,2018GDASCX-0102)。
文摘Skeletal muscle plays a significant role in both local and systemic energy metabolism.The current investigation aims to explore the role of the Bambi gene in skeletal muscle,focusing on its implications for muscle hypertrophy and systemic metabolism.We hypothesize that skeletal muscle-specific deletion of Bambi induces muscle hypertrophy,improves metabolic performance,and activates thermogenic adipocytes via the reprogramming of progenitor of iWAT,offering potential therapeutic strategies for metabolic syndromes.Leveraging the Chromatin immunoprecipitation(ChIP)-seq and bioinformatics analysis,Bambi gene is shown to be a direct target of HIF2α,which is further confirmed by ChIP-qPCR and promoter luciferase assay.Skeletal muscle-specific Bambi deletion led to significant muscle hypertrophy and improved metabolic parameters,even under high-fat diet conditions.This deletion induced metabolic reprogramming of stromal vascular fractions(SVFs)into thermogenic adipocytes,contributing to systemic metabolic improvements,potentially through the secretory factor.Notably,mice with skeletal muscle-specific Bambi deletion demonstrate resistance to high-fat diet-induced metabolic disorders,highlighting a potential therapeutic pathway for metabolic syndrome management.Thus,skeletal muscle-specific deletion of Bambi triggers muscle growth,enhances metabolic performance,and activates thermogenic adipocytes.These findings suggest Bambi as a novel therapeutic target for metabolic syndromes,providing new insights into the interaction between muscle hypertrophy and systemic metabolic improvement.The study underscores the potential of manipulating muscle physiology to regulate whole-body metabolism,offering a novel perspective on treating metabolic disorders.
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grants(81730022,81800758,and 81870601)from the National Nature Science Foundation of Chinaa grant from the National Key R&D Program of China(2018YFC2000100).
文摘Increasing brown and beige fat thermogenesis have an anti-obesity effect and thus great metabolic benefits.However,the molecular mechanisms regulating brown and beige fat thermogenesis remain to be further elucidated.We recently found that fat-specific knockout of Rheb promoted beige fat thermogenesis.In the current study,we show that Rheb has distinct effects on thermogenic gene expression in brown and beige fat.Fat-specific knockout of Rheb decreased protein kinase A(PKA)activity and thermogenic gene expression in brown adipose tissue of high-fat diet-fed mice.On the other hand,overexpression of Rheb activated PKA and increased uncoupling protein 1 expression in brown adipocytes.Mechanistically,Rheb overexpression in brown adipocytes increased Notch expression,leading to disassociation of the regulatory subunit from the catalytic subunit of PKA and subsequent PKA activation.Our study demonstrates that Rheb,by selectively modulating thermogenic gene expression in brown and beige adipose tissues,plays an important role in regulating energy homeostasis.
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。
