Article
Multidisciplinary Sciences
Qiqiao Du, Jieyu Wu, Carina Fischer, Takahiro Seki, Xu Jing, Juan Gao, Xingkang He, Kayoko Hosaka, Le Tong, Akihiro Yasue, Masato Miyake, Mitsuaki Sobajima, Seiichi Oyadomari, Xiaoting Sun, Yunlong Yang, Qinjun Zhou, Minghua Ge, Wei Tao, Shuzhong Yao, Yihai Cao
Summary: This study demonstrates that the mass and functions of brown adipose tissue (BAT) in adult animals can be controlled by manipulating BAT adipocyte differentiation in vivo. Inhibition of PDGFR alpha leads to an increase in brown adipocyte numbers and the formation of enlarged BAT. The study also shows that megaBAT significantly improves global metabolism, insulin sensitivity, high-fat-diet-induced obesity, and diabetes.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Biochemistry & Molecular Biology
Qiang Cao, Shirong Wang, Huan Wang, Xin Cui, Jia Jing, Liqing Yu, Hang Shi, Bingzhong Xue
Summary: The study found that circulating fatty acids and norepinephrine may be key factors for maintaining brown fat thermogenic function and body temperature in the absence of sympathetic innervation into brown adipose tissue.
Article
Endocrinology & Metabolism
Grace Park, John A. Haley, Johnny Le, Su Myung Jung, Timothy P. Fitzgibbons, Ekaterina D. Korobkina, Huawei Li, Shelagh M. Fluharty, Qingbo Chen, Jessica B. Spinelli, Chinmay M. Trivedi, Cholsoon Jang, David A. Guertin
Summary: Adaptive thermogenesis by brown adipose tissue (BAT) plays an important role in dissipating calories as heat and can potentially be used as an anti-obesity target. This study quantified metabolite exchange in BAT and skeletal muscle during cold exposure in mice, revealing unexpected metabolites consumed, released, and shared between organs. Glucose and lactate were found to provide the majority of carbon for adaptive thermogenesis, and cold adaptation triggered different fuel utilization profiles compared to the drug CL316,243. BAT was also found to significantly increase nitrogen uptake during cold adaptation, except for the amino acid glutamine. This study provides valuable insights into the fuel utilization of BAT and its potential implications for future research in this field.
Article
Biology
Fenfen Li, Xin Cui, Jia Jing, Shirong Wang, Huidong Shi, Bingzhong Xue, Hang Shi
Summary: The deletion of Dnmt3b in brown fat of female mice promotes thermogenesis and mitochondrial function, reduces adiposity, and improves insulin sensitivity. Furthermore, Dnmt3b deficiency in brown fat also prevents diet-induced obesity and insulin resistance in female mice. There is sexual dimorphism observed in this model, as male mice do not show changes in body weight when Dnmt3b is knocked out. Overall, Dnmt3b plays a crucial role in regulating brown fat function, energy metabolism, and obesity in female mice.
Article
Cell Biology
Alba Sabate-Perez, Montserrat Romero, Paula Sanchez-Fernandez-de-Landa, Stefania Carobbio, Michail Mouratidis, David Sala, Pablo Engel, Josep A. Villena, Sam Virtue, Antonio Vidal-Puig, Manuel Palacin, Xavier Testar, Antonio Zorzano
Summary: The study reveals a novel molecular mechanism by which TP53INP2 regulates PPARG activity and brown adipogenesis through autophagy, and demonstrates the importance of TP53INP2 in maintaining thermogenic capacity and preventing lipid accumulation in brown adipose tissue. These findings provide insights into the therapeutic strategies against obesity and its metabolic complications.
Article
Biochemistry & Molecular Biology
Shirong Wang, Qiang Cao, Xin Cui, Jia Jing, Fenfen Li, Huidong Shi, Bingzhong Xue, Hang Shi
Summary: This study reveals that deficiency of Dnmt3b in brown fat leads to obesity and decreased energy expenditure, as well as impaired cold-induced thermogenesis. RNA-seq analysis further indicates upregulation of myogenic markers in brown fat of 3bKO mice, suggesting a myocyte-like remodeling.
Article
Biochemistry & Molecular Biology
Lei Hao, Yong-Hui Nie, Chih-Yu Chen, Xiang-Yong Li, Kanakaraju Kaliannan, Jing X. Kang
Summary: This study utilized a transgenic fat-1 mouse model to investigate the regulation of brown adipose tissue (BAT) morphology and function by n-3 polyunsaturated fatty acids (n-3 PUFAs). The findings showed that elevated tissue levels of n-3 PUFAs can alleviate high-fat diet-induced obesity by enhancing thermogenesis and reducing inflammation in BAT.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Medicine, Research & Experimental
Min Jia, Tongcheng Xu, Yong-Jiang Xu, Yuanfa Liu
Summary: Brown adipose tissue (BAT) and beige fat have the potential to fight obesity and chronic diseases by rapidly consuming fatty acids and dissipating energy. This review summarizes the effects of dietary fatty acids on thermogenic adipose tissue, including activation and deactivation of BAT and beige fat.
Article
Cell Biology
Kyung Cheul Shin, Jin Young Huh, Yul Ji, Ji Seul Han, Sang Mun Han, Jeu Park, Hahn Nahmgoong, Won Taek Lee, Yong Geun Jeon, Bohyeon Kim, Chanyoon Park, Heonjoong Kang, Sung Sik Choe, Jae Bum Kim
Summary: The VLDL-VLDLR axis plays a crucial role in the thermogenic execution in brown adipocytes. VLDLR-mediated VLDL uptake provides energy sources for mitochondrial oxidation via lysosomal processing, thereby enhancing thermogenic activity in brown adipocytes. Additionally, the VLDL-VLDLR axis potentiates PPARD/8 activity and thermogenic gene expression in BAT, contributing to the thermogenic capacity.
Article
Endocrinology & Metabolism
Vanessa M. Lima, Jianming Liu, Bruna B. Brandao, Caroline A. Lino, Camila S. Balbino Silva, Marcio A. C. Ribeiro, Tiago E. Oliveira, Caroline C. Real, Daniele de Paula Faria, Carly Cederquist, Zhan-Peng Huang, Xiaoyun Hu, Maria Luiza Barreto-Chaves, Julio C. B. Ferreira, William T. Festuccia, Marcelo A. Mori, C. Ronald Kahn, Da-Zhi Wang, Gabriela P. Diniz
Summary: miR-22 plays a role in white, beige, and brown adipocyte differentiation. Deletion of miR-22 reduces white adipocyte differentiation, increases BAT activity, and enhances resistance in HFD-fed mice.
METABOLISM-CLINICAL AND EXPERIMENTAL
(2021)
Article
Multidisciplinary Sciences
Shengnan Liu, Siyi Shen, Ying Yan, Chao Sun, Zhiqiang Lu, Hua Feng, Yiruo Ma, Zhili Tang, Jing Yu, Yuting Wu, Balazs Gereben, Petra Mohacsik, Csaba Fekete, Xiaoyun Feng, Feixiang Yuan, Feifan Guo, Cheng Hu, Mengle Shao, Xin Gao, Lin Zhao, Yuying Li, Jingjing Jiang, Hao Ying
Summary: The active form of thyroid hormone, T3, promotes the proliferation of adipocyte progenitor cells in brown adipose tissue, leading to increased thermogenic capacity.
NATURE COMMUNICATIONS
(2022)
Article
Multidisciplinary Sciences
Donghua Hu, Min Tan, Dongliang Lu, Brian Kleiboeker, Xuejing Liu, Hongsuk Park, Alexxai V. Kravitz, Kooresh I. Shoghi, Yu-Hua Tseng, Babak Razani, Akihiro Ikeda, Irfan J. Lodhi
Summary: Mitochondrial morphology, regulated by fission and fusion, plays a crucial role in the thermogenic capacity of brown adipocytes. TMEM135 has been identified as a critical mediator in the regulation of mitochondrial fission and thermogenesis, providing a potential target for therapeutic activation of brown adipose tissue.
NATURE COMMUNICATIONS
(2023)
Article
Endocrinology & Metabolism
Aurelie Fabre, Blandine Tramunt, Alexandra Montagner, Celine Mouly, Elodie Riant, Marie-Lou Calmy, Marine Adlanmerini, Coralie Fontaine, Remy Burcelin, Francoise Lenfant, Jean-Francois Arnal, Pierre Gourdy
Summary: This study found that membrane receptor ERa is involved in the protective metabolic actions of endogenous estrogens in conditions of nutritional challenge, contributing to sex differences in the susceptibility to metabolic diseases. Female mice with C451A-ERa genotype exhibited accelerated fat mass accumulation, liver steatosis, impaired glucose tolerance, whole-body insulin resistance, and decreased energy expenditure under a high-fat diet condition. These findings highlight the importance of membrane-initiated ERa signaling in female protection against obesity and associated metabolic disorders.
FRONTIERS IN ENDOCRINOLOGY
(2023)
Article
Multidisciplinary Sciences
Birte Niemann, Saskia Haufs-Brusberg, Laura Puetz, Martin Feickert, Michelle Y. Jaeckstein, Anne Hoffmann, Jelena Zurkovic, Markus Heine, Eva-Maria Trautmann, Christa E. Mueller, Anke Toenjes, Christian Schlein, Azin Jafari, Holger K. Eltzschig, Thorsten Gnad, Matthias Bluher, Natalie Krahmer, Peter Kovacs, Joerg Heeren, Alexander Pfeifer
Summary: This study reveals that inosine, a metabolite released during apoptosis, enhances the thermogenic program in healthy adipocytes and regulates energy expenditure. The equilibrative nucleoside transporter 1 (ENT1) controls inosine levels in brown adipose tissue, affecting thermogenic capacity. In humans, a loss of function mutation in ENT1 is associated with lower body mass index and reduced odds of obesity.
Article
Immunology
Lijun Xie, Huiying Wang, Dan Wu, Feng Zhang, Wei Chen, Yuqing Ye, Fang Hu
Summary: This study reveals the novel role of adipose chemokine CXCL13 in the regulation of BAT activity and thermogenesis by recruiting M2 macrophages and inhibiting pro-inflammatory factor TNF-alpha level.
FRONTIERS IN IMMUNOLOGY
(2023)
Review
Cardiac & Cardiovascular Systems
Xuexian Fang, Hossein Ardehali, Junxia Min, Fudi Wang
Summary: Iron homeostasis is crucial for proper cardiac function, and iron imbalance is a common factor in various cardiovascular diseases. Ferroptosis, an iron-dependent regulated cell death, has been increasingly recognized as an important process underlying the pathogenesis and progression of cardiovascular diseases. Understanding the mechanisms of iron metabolism and ferroptosis regulation in cardiomyocytes may lead to improvements in disease management.
NATURE REVIEWS CARDIOLOGY
(2023)
Article
Cell Biology
Qian Wu, Euclides Sacomboio, Lara Valente de Souza, Rui Martins, Jamil Kitoko, Silvia Cardoso, Temitope W. Ademolue, Tiago Paixao, Jaakko Lehtimaki, Ana Figueiredo, Caren Norden, Pierre-Louis Tharaux, Guenter Weiss, Fudi Wang, Susana Ramos, Miguel P. Soares
Summary: Iron recycling is important in preventing anemia, and its role in preventing anemia during infection is unclear. In severe Plasmodium falciparum malaria, acute kidney injury (AKI) is associated with life-threatening anemia. A study using a rodent model shows that renal proximal tubule epithelial cells (RPTECs) have the ability to store and recycle iron during P. chabaudi chabaudi (Pcc) infection, preventing the onset of life-threatening malarial anemia.
Article
Multidisciplinary Sciences
Na Li, Bowen Wu, Jifeng Wang, Yumeng Yan, Peng An, Yuezhen Li, Yuning Liu, Yanfei Hou, Xiaoqing Qing, Lili Niu, Xiang Ding, Zhensheng Xie, Mengmeng Zhang, Xiaojing Guo, Xiulan Chen, Tanxi Cai, Jianming Luo, Fudi Wang, Fuquan Yang
Summary: New diagnostic strategies are needed to determine the subtypes of beta-thalassemia and facilitate personalized therapeutic regimens. This study explored the characteristics and potential biomarkers of beta-thalassemia subtypes using quantitative proteomics of plasma-derived extracellular vesicles. The findings showed that the proteomic patterns of extracellular vesicles were consistent with, but more distinct than, those of plasma, and they had superior discriminatory ability for beta-thalassemia subtypes.
Editorial Material
Biochemistry & Molecular Biology
Chang-Zhou Feng, Ning-Zhe Li, Xi-Bo Hu, Yin -Yin Xie, Qiu-Hua Huang, Jianming Zhang, Zhu Chen, Sai-Juan Chen, Fudi Wang, Xiao-Jian Sun
Article
Multidisciplinary Sciences
Xin-yu He, Xiao Fan, Lei Qu, Xiang Wang, Li Jiang, Ling-jie Sang, Cheng-yu Shi, Siyi Lin, Jie-cheng Yang, Zuo-zhen Yang, Kai Lei, Jun-hong Li, Huai-qiang Ju, Qingfeng Yan, Jian Liu, Fudi Wang, Jianzhong Shao, Yan Xiong, Wenqi Wang, Aifu Lin
Summary: In this study, the authors discovered that an iron-triggered long noncoding RNA called LncRIM regulates cellular iron metabolism through the Hippo-YAP signaling pathway, promoting breast cancer development. They found that LncRIM directly binds NF2 to inhibit NF2-LATS1 interaction, leading to YAP activation and increased intracellular iron levels. Clinical data showed that high expression of LncRIM is associated with poor patient survival, indicating its potential as a biomarker and therapeutic target. This study highlights a novel mechanism involving the LncRIM-NF2 axis in iron-mediated feedback loop that hyperactivates YAP and promotes breast cancer development.
NATURE COMMUNICATIONS
(2023)
Article
Chemistry, Multidisciplinary
Xuexian Fang, Jiawei Zhang, You Li, Yijing Song, Yingying Yu, Zhaoxian Cai, Fuzhi Lian, Jun Yang, Junxia Min, Fudi Wang
Summary: In this study, using a mouse model of hepatic I/R injury, it is observed that glutathione (GSH) and cysteine depletion are associated with deficiency of the reducing power of nicotinamide adenine dinucleotide phosphate (NADPH). It is identified that I/R-induced hepatic ferroptosis is significantly associated with reduced expression and activity of NADP(+)-dependent malic enzyme 1 (Me1). Targeting ME1 may provide new therapeutic opportunities for I/R injury and other ferroptosis-related hepatic conditions.
Article
Chemistry, Multidisciplinary
Xuyan He, Chaodong Ge, Jun Xia, Zhidan Xia, Lu Zhao, Sicong Huang, Rong Wang, Jianwei Pan, Tao Cheng, Peng-Fei Xu, Fudi Wang, Junxia Min
Summary: SLC39A10 is identified as a key zinc transporter in hematopoiesis, and it plays a larger role than iron in early hematopoietic stem cells. Loss of Slc39a10 causes zinc deficiency, leading to DNA damage, apoptosis, and cell cycle arrest. Zinc supplementation and inhibiting necroptosis were found to restore hematopoiesis, suggesting the potential of SLC39A10 as a therapeutic target for anemia and zinc deficiency-related disorders.
Review
Oncology
Xue Wang, Ye Zhou, Junxia Min, Fudi Wang
Summary: Ferroptosis is an iron-dependent form of cell death caused by lipid peroxidation and has been implicated in the pathogenesis of various diseases involving multiple organs. Understanding the molecular mechanisms and regulatory pathways of ferroptosis could provide new strategies for disease management. Recent studies support ferroptosis as a potential target for the prevention and treatment of these diseases. This review summarizes the progress in ferroptosis research and its regulation in human disease, and discusses future directions in the targeting of ferroptosis.
FRONTIERS OF MEDICINE
(2023)
Review
Chemistry, Inorganic & Nuclear
Shuying Shen, Jie Shen, Zhong Luo, Fudi Wang, Junxia Min
Summary: Auranofin (AUR) is a lipophilic gold-based compound used for rheumatoid arthritis treatment. It exhibits diverse biological properties, including antibacterial, antiviral, antifungal, antiparasitic, and anticancer activities. Mechanistically, AUR regulates cellular redox homeostasis by inhibiting thioredoxin reductase activity and affects multiple signaling pathways related to cell proliferation, apoptosis, and ferroptosis. Advances in stereospecific chemistry of AUR have identified new targets, offering potential for its use in various clinical indications.
COORDINATION CHEMISTRY REVIEWS
(2023)
Article
Multidisciplinary Sciences
Lu Jin, Shuang Han, Xue Lv, Xiaofei Li, Ziyin Zhang, Henry Kuang, Zhimin Chen, Cheng-an Lv, Wei Peng, Zhuoying Yang, Miqi Yang, Lin Mi, Tongyu Liu, Shengshan Ma, Xinyuan Qiu, Qintao Wang, Xiaowen Pan, Pengfei Shan, Yu Feng, Jin Li, Fudi Wang, Liwei Xie, Xuyun Zhao, Jun-Fen Fu, Jiandie D. Lin, Zhuo-Xian Meng
Summary: The study found that obesity in humans and mice is associated with elevated levels of Musclin in both muscle and circulation. Musclin overexpression attenuates beige fat thermogenesis, exacerbates diet-induced obesity and metabolic disorders. In contrast, Musclin inactivation promotes beige fat thermogenesis and improves metabolic homeostasis. This research provides a new therapeutic approach for treating obesity and metabolic diseases.
NATURE COMMUNICATIONS
(2023)
Article
Biology
Tianze Xu, Jing Cai, Lei Wang, Li Xu, Hongting Zhao, Fudi Wang, Esther G. Meyron-Holtz, Fanis Missirlis, Tong Qiao, Kuanyu Li
Summary: Postmenopausal atherosclerosis (AS) is linked to estrogen deficiency, but hormone replacement therapy (HRT) is ineffective in late postmenopausal women. This study suggests that aging-related iron accumulation inhibits the expression of estrogen receptor a (ERa), explaining the inefficacy of HRT. Iron and estradiol together downregulate ERa through Mdm2-mediated proteolysis, aggravating AS. Systemic iron chelation attenuates progressive AS in late postmenopausal mice triggered by estradiol. Immediate HRT after menopause, along with appropriate iron chelation, could provide benefits from AS.
Review
Biochemistry & Molecular Biology
Jie Fu, Xin Zong, Mingliang Jin, Junxia Min, Fudi Wang, Yizhen Wang
Summary: As cationic host defense peptides, defensins are synthesized by various cells and serve as crucial components of host defense. Recent research has focused on their biological functions, structure-activity relationships, mechanisms of action, and therapeutic potential. This review provides an overview of the roles of defensins in immune homeostasis, mucosal barrier function, gut microbiota regulation, and various diseases, as well as their regulation by nutrients. It offers important insights into the biology and potential clinical applications of defensins.
SIGNAL TRANSDUCTION AND TARGETED THERAPY
(2023)
Review
Urology & Nephrology
Xihao Cheng, Chao Yu, Xinquan Yang, Fudi Wang, Junxia Min
Summary: A review of the latest progress in the field of ferroptosis in cardiovascular disease (CVD) reveals that ferroptosis plays a pathogenic role in various forms of CVD, and targeting ferroptosis through modulation of iron metabolism, lipid metabolism, and oxidative metabolism represents a promising approach for the prevention and treatment of CVD.
Review
Cell & Tissue Engineering
Qin Ru, Yusheng Li, Wenqing Xie, Yilan Ding, Lin Chen, Guodong Xu, Yuxiang Wu, Fudi Wang
Summary: Ferroptosis, a unique form of cell death driven by iron accumulation and lipid peroxidation, is closely associated with iron metabolism, polyunsaturated fatty acid metabolism, and antioxidant pathways. Recent research has revealed a potential link between ferroptosis and age-related orthopedic diseases, such as osteoporosis and osteoarthritis. Understanding the regulatory mechanisms of ferroptosis in these diseases could lead to improved treatment and prevention strategies.
Article
Gastroenterology & Hepatology
Qiuyuan Yang, Yue Wu, Wei Liu, Xiaojuan Ou, Wei Zhang, Jianning Wang, Yanzhong Chang, Fudi Wang, Ming Gao, Sijin Liu
Summary: Our study explores the role of iron in liver lipid metabolism and finds that iron overload can disrupt the normal distribution of lipids within the liver, particularly in the periportal zone. Through gene expression analysis in both the pericentral and periportal zones, we identify pyruvate carboxylase (PC) as a key regulator in iron overload-induced lipid accumulation. We also reveal that the activation of cyclic adenosine monophosphate response element binding protein (CREB) is essential for Pc gene expression in response to iron overload.
LIVER INTERNATIONAL
(2023)