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Global gene expression profiling of perirenal brown adipose tissue whitening in goat kids reveals novel genes linked to adipose remodeling

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Journal of Animal Science and Biotechnology 2024年第3期15卷 1008-1026页

作者： Le Zhao Haili Yang Minhao Li Min Xiao Xingchun Li Lei Cheng Wenqiang Cheng Meixi Chen Yongju Zhao College of Animal Science and Technology Southwest UniversityChongqing Key Laboratory of Herbivore ScienceChongqing 400715China

Background brown adipose tissue(BAT)is known to be capable of non-shivering thermogenesis under cold stimulation,which is related to the mortality of animals.In the previous study,we observed that goat BAT is mainly located around the kidney at birth,and changes to white adipose tissue(WAT)in the perirenal adipose tissue of goats within one month after birth.However,the regulatory factors underlying this change is remain unclear.In this study,we systematically studied the perirenal adipose tissue of goat kids in histological,cytological,and accompanying molecular level changes from 0 to 28 d after birth.Results Our study found a higher mortality rate in winter-born goat kids,with goat birthing data statistics.Then we used thermal imaging revealing high temperature in goat hips at postnatal 0 d and gradually decrease during 28 d.This is consistent with the region of perirenal BAT deposition and highlights its critical role in energy expenditure and body temperature regulation in goat kids.Additionally,we found a series of changes of BAT during the first 28 d after birth,such as whitening,larger lipid droplets,decreased mitochondrial numbers,and down-regulation of key thermogenesis-related genes(UCP1,DIO2,UCP2,CIDEA,PPARGC1a,C/EBPb,and C/EBPa).Then,we used RNA-seq found specific marker genes for goat adipose tissue and identified 12 new marker genes for BAT and 10 new marker genes for WAT of goats.Furthermore,12 candidate genes were found to potentially regulate goat BAT thermogenesis.The mechanism of the change of this biological phenomenon does not involve a large-scale death of brown adipocytes and subsequent proliferation of white adipocytes.While apoptosis may play a limited role,it is largely not critical in this transition process.Conclusions We concluded that perirenal BAT plays a crucial role in thermoregulation in newborn goat kids,with notable species differences in the expression of adipose tissue marker genes,and we highlighted some potential marker genes for goat BAT and WAT.Additionally,the change fr

关键词： adipose remodeling brown adipose tissue Goat kids Key thermogenesis-related genes Whitening

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Orexin receptor type 2 agonism inhibits thermogenesis in brown adipose tissue by attenuating afferent innervation

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The Journal of Biomedical Research 2022年第3期36卷 195-207,I0005,I0006页

作者： Mo-qiu Jia Yong-jin Wang Kang Fu Han Jiao Jia Sun Yuanqing Gao Key Laboratory of Cardiovascular and Cerebrovascular Medicine School of PharmacyNanjing Medical UniversityNanjingJiangsu 211166China

Orexin signaling has been associated with energy expenditure and brown adipose tissue(BAT)function.However,conflicting data exist in the field about how orexin signaling regulates BAT thermogenesis.In this study,we show that a specific orexin receptor type 2(OX2R)agonist[Ala11,D-Leu15]-OxB(OB-Ala)inhibited intrascapular brown adipose tissue(iBAT)thermogenesis by reducing sympathetic output to iBAT.This effect is mediated by OX2Rs located on afferent nerve endings innervating iBAT instead of brown adipocyte itself.Microinjection of OB-Ala into iBAT inhibited iBAT thermogenesis in mice upon cold exposure and neuronal activity in the paraventricular nucleus.Findings suggest that OB-Ala could inhibit iBAT thermogenesis by attenuating sensory input thereby inhibiting the sympathetic-sensory iBAT feedback loop.Our study uncovers a novel primary action site of orexin in the regulation of energy balance.

关键词： orexin receptor type 2 brown adipose tissue thermogenesis

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brown adipose tissue and its therapeutic application

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Science Bulletin 2016年第19期61卷 1498-1503,1469页

作者：袁晓雪董孟李赫钟金万洙 Key Laboratory of Animal Ecology and Conservation Biology Institute of Zoology Chinese Academy of Sciences The University of the Chinese Academy of Sciences

除了储存能量的白色脂肪组织(Whiteadiposetissue,WAT),人类和小型哺乳动物体内也存在着消耗能量的棕色脂肪组织(brownadiposetissue BAT).BAT对于小型哺乳动物和人类婴儿的体温维持具有重要作用.棕色脂肪细胞内含有很多小脂滴和丰富的... 详细信息

除了储存能量的白色脂肪组织(Whiteadiposetissue,WAT),人类和小型哺乳动物体内也存在着消耗能量的棕色脂肪组织(brownadiposetissue BAT).BAT对于小型哺乳动物和人类婴儿的体温维持具有重要作用.棕色脂肪细胞内含有很多小脂滴和丰富的血管、神经和线粒体.棕色脂肪的线粒体通过去偶联反应把ATP转化成热量.近年来的研究结果表明,增加棕色脂肪的数量或者提高棕色脂肪的活性可以抑制高脂饮食诱导的体重增加,改善胰岛素抵抗,治疗肥胖.这说明棕色脂肪很可能是防治肥胖以及相关疾病的强有力的靶器官.本文综述了近年来有关棕色脂肪在改善代谢功能、激活棕色脂肪和米色脂肪的相关因子以及其临床运用等方面的研究进展.

关键词： brown adipose tissue Lipid metabolism Therapeutic application

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Medium-Chain Triglyceride Activated brown adipose tissue and Induced Reduction of Fat Mass in C57BL/6J Mice Fed High-fat Diet

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Biomedical and Environmental Sciences 2015年第2期28卷 97-104页

作者： ZHANG Yong XU Qing LIU Ying Hua ZHANG Xin Sheng WANG Jin YU Xiao Ming ZHANG Rong Xin XUE Chao YANG Xue Yan XUE Chang Yong Department of Nutrition Chinese PLA General Hospital Peking University Health Science Center

Objective To investigate activation of brown adipose tissue （BAT） stimulated by medium-chain triglyceride （MCT）. Methods 30 Male C57BL/6J obese mice induced by fed high fat diet （HFD） were divided into 2 groups, and fed another HFD with 2% MCT or long-chain triglyceride （LCT） respectively for 12 weeks. Body weight, blood biochemical variables, interscapular brown fat tissue （IBAT） mass, expressions of mRNA and protein of beta 3-adrenergic receptors （β3-AR）, uncoupling protein-1 （UCP1）, hormone sensitive lipase （HSL）, protein kinase A （PKA）, and adipose triglyceride lipase （ATGL） in IBAT were measured. Results Significant decrease in body weight and body fat mass was observed in MCT group as compared with LCT group （P〈O.05） after 12 weeks. Greater increases in IBAT mass was observed in MCT group than in LCT group （P〈O.05）. Blood TG, TC, LDL-C in MCT group were decreased significantly, meanwhile blood HDL-C, ratio of HDL-C/LDL-C and norepinephrine were increased markedly. Expressions of mRNA and protein of β3-AR, UCP1, PKA, HSL, ATGL in BAT were greater in MCT group than in LCT group （P〈O.05）. Conclusion Our results suggest that MCT stimulated the activation of BAT, possible via norepinephrine pathway, which might partially contribute to reduction of the body fat mass in obese mice fed high fat diet.

关键词： Medium-chain triglyceride brown adipose tissue Uncoupling protein-l Beta 3-adrenergicreceptor

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Role of brown adipose tissue in metabolic syndrome, aging, and cancer cachexia

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Frontiers of Medicine 2018年第2期12卷 130-138页

作者： Meng Dong Jun Lin Wonchung Lim Wanzhu Jin Hyuek Jong Lee Key Laboratory of Animal Ecology and Conservation Biology Institute of Zoology Chinese Academy of Sciences Beijing 100101 China The University of the Chinese Academy of Sciences Beijing 100049 China Department of Sports Medicine College of Health ScienceCheongju University Cheongju 363-764 Republic of Korea Center for Vascular Research Institute for Basic Science (IBS) Daejeon 34141 Republic of Korea

brown adipose tissue （BAT） plays a fundamental role in maintaining body temperature by producing heat. BAT that had been know to exist only in mammals and the human neonate has received great attention for the treatment of obesity and diabetes due to its important function in energy metabolism, ever since it is recently reported that human adults have functional BAT. In addition, beige adipocytes, brown adipocytes in white adipose tissue （WAT）, have also been shown to take part in whole body metabolism. Multiple lines of evidence demonstrated that transplantation or activation of BAT or/and beige adipocytes reversed obesity and improved insulin sensitivity. Furthermore, many genes involved in BAT activation and/or the recruitment of beige cells have been found, thereby providing new promising strategies for future clinical application of BAT activation to treat obesity and metabolic diseases. This review focuses on recent advances of BAT function in the metabolic aspect and the relationship between BAT and cancer cachexia, a pathological process accompanied with decreased body weight and increased energy expenditure in cancer patients. The underlying possible mechanisms to reduce BAT mass and its activity in the elderly are also discussed.

关键词： brown adipose tissue beige adipocyte anti-obesity anti-diabetes cancer cachexia aging

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Medium-Chain Triglyceride Activated brown adipose tissue and Induced Reduction of Fat Mass in C57BL/6J Mice Fed High-Fat Diet

Medium-Chain Triglyceride Activated Brown Adipose Tissue and...

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第十四届全国临床营养学术会议

作者： ZHANG Yong XU Qing LIU Ying hua ZHANG Xin sheng WANG Jin YU Xiao ming ZHANG Rong xin XUE Chao YANG Xue yan XUE Chang yong Department of Nutrition Chinese PLA General Hospital Summer student from Peking University Health Science Center

Objective To investigate activation of brown adipose tissue(BAT)stimulated by medium-chain triglyceride(MCT).Methods 30 Male C57BL/6J obese mice induced by fed high fat diet(HFD) were divided into 2 groups,and fed another HFD with 2%MCT or long-chain triglyceride(LCT) respectively for 12 weeks.Body weight,blood biochemical variables,interscapular brown fat tissue(IBAT) mass,expressions of mRNA and protein of beta 3-adrenergic receptors(β3-AR),uncoupling protein-1(UCPl),hormone sensitive lipase(HSL),protein kinase A(PKA) and adipose triglyceride lipase(ATGL) in IBAT were measured.Results Significant decrease in body weight and body fat mass was observed in MCT group as compared with LCT group(P<0.05) after 12 weeks.Greater increases in IBAT mass was observed in MCT group than in LCT group(P<0.05).Blood TG,TC,LDL-C in MCT group were decreased significantly,meanwhile blood HDL-C,ratio of HDL-C/LDL-C and norepinephrine were increased markedly.Expressions of mRNA and protein of B3 AR,UCPl,PKA,HSL,ATGL in BAT were greater in MCT group than in LCT group(P<0.05).Conclusion Our results suggest that MCT stimulated the activation of BAT,possible via norepinephrine pathway,which might partially contribute to reduction of the body fat mass in obese mice fed high fat diet.

关键词： Medium-chain triglyceride brown adipose tissue Uncoupling protein-1 Beta 3-adrenergic receptor

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Recent developments in natural products for white adipose tissue browning

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Chinese Journal of Natural Medicines 2020年第11期18卷 803-817页

作者： MA Peng HE Ping XU Chun-Yang HOU Bi-Yu QIANG Gui-Fen DU Guan-Hua State Key Laboratory of Bioactive Substance and Function of Natural Medicines Instiute of Materia MedicaChinese Academy of Medical Sciences and Peking Union Medical College and Bejing Key Laboratory of Drug Target and Screening ResearchBeijing 100050China Beijing Obstetrics and Gyecology Hospital Capital Medical UniversityBeijing 100026China

Excess accumulation of white adipose tissue(WAT) causes obesity which is an imbalance between energy intake and energy expenditure. Obesity is a serious concern because it has been the leading causes of death worldwide, including diabetes, stroke,heart disease and cancer. Therefore, uncovering the mechanism of obesity and discovering anti-obesity drugs are crucial to prevent obesity and its complications. browning, inducing white adipose tissue to brown or beige(brite) fat which is brown-like fat emerging in WAT, becomes an appealing therapeutic strategy for obesity and metabolic disorders. Due to lack of efficacy or intolerable side-effects, the clinical trials that promote brown adipose tissue(BAT) thermogenesis and browning of WAT have not been successful in humans. Obviously, more specific means still need to be developed to activate browning of white adipose tissue. In this review, we summarized seven kinds of natural products(alkaloids, flavonoids, terpenoids, long chain fatty acids, phenolic acids, else and extract) promoting white adipose tissue browning which can ameliorate the metabolic disorders, including obesity, dislipidemia, insulin resistance and diabetes. Since natural products are important drug sources and the browning property plays a significant role in not only obesity treatment but also in type 2 diabetes(T2 DM) improvement, natural products of inducing browning may be an irreplaceable drug discovery orientation for obesity, diabetes and even other metabolic disorders.

关键词： Natural products browning brown adipose tissue White adipose tissue Obesity

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Mulberry leaf flavonoids activate BAT and induce browning of WAT to improve type 2 diabetes via regulating the AMPK/SIRT1/PGC-1α signaling pathway

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Chinese Journal of Natural Medicines 2023年第11期21卷 812-829页

作者： CHENG Long SHI Lu HE Changhao WANG Chen LV Yinglan LI Huimin AN Yongcheng DUAN Yuhui DAI Hongyu ZHANG Huilin HUANG Yan FU Wanxin SUN Weiguang ZHAO Baosheng School of Chinese Materia Medica Beijing University of Chinese MedicineBeijing 102488China Department of Pharmacognosy School of PharmacyChina Medical UniversityShenyang 110122China College of Life Sciences Beijing University of Chinese MedicineBeijing 102488China GuangZhou Baiyunshan Xingqun Pharmaceutical Co. Ltd.Guangzhou 510288China Beijing Research Institute of Chinese Medicine Beijing University of Chinese MedicineBeijing 100029China

Mulberry (Morus alba L.) leaf is a well-established traditional Chinese botanical and culinary resource. It has found widespread application in the management of diabetes. The bioactive constituents of mulberry leaf, specifically mulberry leaf flavonoids (MLFs), exhibit pronounced potential in the amelioration of type 2 diabetes (T2D). This potential is attributed to their ability to safeguard pancreatic β cells, enhance insulin resistance, and inhibit α-glucosidase activity. Our antecedent research findings underscore the substantial therapeutic efficacy of MLFs in treating T2D. However, the precise mechanistic underpinnings of MLF’s anti-T2D effects remain the subject of inquiry. Activation of brown/beige adipocytes is a novel and promising strategy for T2D treatment. In the present study, our primary objective was to elucidate the impact of MLFs on adipose tissue browning in db/db mice and 3T3-L1 cells and elucidate its underlying mechanism. The results manifested that MLFs reduced body weight and food intake, alleviated hepatic steatosis, improved insulin sensitivity, and increased lipolysis and thermogenesis in db/db mice. Moreover, MLFs activated brown adipose tissue (BAT) and induced the browning of inguinal white adipose tissue (IWAT) and 3T3-L1 adipocytes by increasing the expressions of brown adipocyte marker genes and proteins such as uncoupling protein 1 (UCP1) and beige adipocyte marker genes such as transmembrane protein 26 (Tmem26), thereby promoting mitochondrial biogenesis. Mechanistically, MLFs facilitated the activation of BAT and the induction of WAT browning to ameliorate T2D primarily through the activation of AMP-activated protein kinase (AMPK)/sirtuin 1 (SIRT1)/peroxisome proliferator-activated receptor-gamma coactivator 1α (PGC-1α) signaling pathway. These findings highlight the unique capacity of MLF to counteract T2D by enhancing BAT activation and inducing browning of IWAT, thereby ameliorating glucose and lipid metabolism disorders. As such, MLFs emerge as a prospective and innovative

关键词： Mulberry leaf flavonoids brown adipose tissue browning of white adipose tissue Type 2 diabetes AMPK/SIRT1/PGC-1α

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Population genomics reveals that natural variation in PRDM16 contributes to cold tolerance in domestic cattle

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Zoological Research 2022年第2期43卷 275-284页

作者： Chun-Long Yan Jun Lin Yuan-Yuan Huang Qing-Shan Gao Zheng-Yu Piao Shou-Li Yuan Li Chen Xue Ren Rong-Cai Ye Meng Dong Han-Lin Zhang Hui-Qiao Zhou Xiao-Xiao Jiang Wan-Zhu Jin Xu-Ming Zhou Chang-Guo Yan College of Agriculture Yanbian UniversityYanjiJilin 133000China Key Laboratory of Animal Ecology and Conservation Biology Institute of ZoologyChinese Academy of SciencesBeijing 100101China University of Chinese Academy of Sciences Beijing 100049China North-East Cold Region Beef Cattle Science&Technology Innovation Ministry of Education Engineering Research Center Yanbian UniversityYanjiJilin 133000China Annoroad Gene Technology Co.Ltd Beijing 100176China

Environmental temperature serves as a major driver of adaptive changes in wild organisms.To discover the mechanisms underpinning cold tolerance in domestic animals,we sequenced the genomes of 28 cattle from warm and cold areas across China.By characterizing the population structure and demographic history,we identified two genetic clusters,i.e.,northern and southern groups,as well as a common historic population peak at 30 kilo years ago.Genomic scan of cold-tolerant breeds determined potential candidate genes in the thermogenesis-related pathways that were under selection.Specifically,functional analysis identified a substitution of PRDM16(p.P779 L)in northern cattle,which maintains brown adipocyte formation by boosting thermogenesis-related gene expression,indicating a vital role of this gene in cold tolerance.These findings provide a basis for genetic variation in domestic cattle shaped by environmental temperature and highlight the role of reverse mutation in livestock species.

关键词： Population genomics Cattle Cold tolerance PRDM16 brown adipose tissue

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Chchd10 is dispensable for myogenesis but critical for adipose browning

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Cell Regeneration 2022年第1期11卷 131-145页

作者： Wei Xia Jiamin Qiu Ying Peng Madigan MSnyder Lijie Gu Kuilong Huang Nanjian Luo Feng Yue Shihuan Kuang College of Animal Science and Technology Hebei Agricultural UniversityBaoding 071000China Department of Animal Sciences Purdue UniversityWest LafayetteIN 47907USA College of Animal and Veterinary Science Southwest Minzu UniversityChengdu 610041China College of Biological Sciences China Agricultural UniversityBeijing 100193China

The Chchd10 gene encodes a coiled-coil-helix-coiled-coil-helix-domain containing protein predicted to function in the mitochondrion and nucleus.Mutations of Chchd10 are associated with ALS,dementia and myopathy in humans and animal models,but how knockout of Chchd10(Chchd10KO)affects various tissues especially skeletal muscle and adipose tissues remains unclear.Here we show that Chchd10 expression increases as myoblasts and preadipocytes dif-ferentiate.During myogenesis,CHCHD10 interacts with TAR DNA binding protein 43(TDP-43)in regenerating myofib-ers in vivo and in newly differentiated myotubes ex vivo.Surprisingly,Chchd10KO mice had normal skeletal muscle development,growth and regeneration,with moderate defects in grip strength and motor performance.Chchd10KO similarly had no effects on development of brown and white adipose tissues(WAT).However,Chchd10KO mice had blunted response to acute cold and attenuated cold-induced browning of WAT,with markedly reduced UCP1 levels.Together,these results demonstrate that Chchd10 is dispensable for normal myogenesis and adipogenesis but is required for normal motility and cold-induced,mitochondrion-dependent browning of adipocytes.The data also sug-gest that human CHCHD10 mutations cause myopathy through a gain-of-function mechanism.

关键词： Skeletal muscle Myoblasts Regeneration Adipocyte brown adipose tissue Uncoupling protein 1(UCP1)

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