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Transcriptional and epigenetic control of brown and beige adipose cell fate and function (vol 17, pg 480, 2016)

NATURE REVIEWS MOLECULAR CELL BIOLOGY (2017)

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NATURE REVIEWS MOLECULAR CELL BIOLOGY

卷 18, 期 8, 页码 -

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NATURE PUBLISHING GROUP

DOI: 10.1038/nrm.2017.72

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Latest Advancements on Combating Obesity by Targeting Human Brown/Beige Adipose Tissues

Ruping Pan, Yong Chen

Summary: Obesity is characterized by the overaccumulation of white adipose tissue in the body, leading to various metabolic disorders. Targeting human thermogenic adipose tissues shows promise in combating obesity.

FRONTIERS IN ENDOCRINOLOGY (2022)

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Brown and beige adipose tissue regulate systemic metabolism through a metabolite interorgan signaling axis

Anna Whitehead, Fynn N. Krause, Amy Moran, Amanda D. V. MacCannell, Jason L. Scragg, Ben D. McNally, Edward Boateng, Steven A. Murfitt, Samuel Virtue, John Wright, Jack Garnham, Graeme R. Davies, James Dodgson, Jurgen E. Schneider, Andrew J. Murray, Christopher Church, Antonio Vidal-Puig, Klaus K. Witte, Julian L. Griffin, Lee D. Roberts

Summary: The study identifies a group of metabolites synthesized in brown adipose tissue that can influence the metabolism of fat tissue and skeletal muscle, with anti-obesity effects in mouse models of obesity and diabetes. Brown and beige adipose tissue appear to have a significant impact on systemic metabolism through secreted signals.

NATURE COMMUNICATIONS (2021)

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Optogenetic activation of UCP1-dependent thermogenesis in brown adipocytes

Chad C. Doucette, Davide Barteselli, Daniel C. Nguyen, Sophia Blanchard, Mason Pelletier, Devesh Kesharwani, Ed Jachimowicz, Su Su, Michele Karolak, Aaron C. Brown

Summary: In this study, an optogenetic approach was used to activate UCP1-dependent thermogenesis in brown adipocytes. This system allows for precise, chemical free, temporal control of UCP1-dependent thermogenesis, which can contribute to our understanding of brown adipocyte biology and the development of therapies for obesity-related disorders.

ISCIENCE (2023)

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Apoptotic brown adipocytes enhance energy expenditure via extracellular inosine

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.

NATURE (2022)

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Review Endocrinology & Metabolism

An insight into brown/beige adipose tissue whitening, a metabolic complication of obesity with the multifactorial origin

Khanyisani Ziqubu, Phiwayinkosi V. Dludla, Sinenhlanhla X. H. Mthembu, Bongani B. Nkambule, Sihle E. Mabhida, Babalwa U. Jack, Tawanda M. Nyambuya, Sithandiwe E. Mazibuko-Mbeje

Summary: Brown adipose tissue (BAT) has been extensively studied as a potential avenue to combat obesity due to its thermoregulatory function and energy expenditure promotion. In obesity, BAT and beige adipose tissue exhibit whitening characteristics, which are associated with various factors including diet, age, genetics, thermoneutrality, and chemical exposure. Whitening is marked by the accumulation of large unilocular lipid droplets, mitochondrial degeneration, and collapsed thermogenic capacity, by the virtue of mitochondrial dysfunction, devascularization, autophagy, and inflammation.

FRONTIERS IN ENDOCRINOLOGY (2023)

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Review Pharmacology & Pharmacy

Endocrine disrupting chemicals: Friend or foe to brown and beige adipose tissue?

Cynthia E. Francis, Logan Allee, Helen Nguyen, Rachel D. Grindstaff, Colette N. Miller, Srujana Rayalam

Summary: The effects of EDCs on obesity are of growing interest, with potential to increase the risk of obesity by altering energy metabolism in adipose tissues. Brown and beige fat, rich in mitochondria and involved in metabolic diseases, are highlighted as potential therapeutic targets.

TOXICOLOGY (2021)

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Review Nutrition & Dietetics

Brown Fat and Nutrition: Implications for Nutritional Interventions

Lloyd Noriega, Cheng-Ying Yang, Chih-Hao Wang

Summary: Brown and beige adipocytes have the ability to generate heat and can be activated by various methods. Understanding the molecular mechanisms of their differentiation and function is crucial for developing clinical therapies. Drugs and nutritional interventions can activate these adipocytes while minimizing potential side effects.

NUTRIENTS (2023)

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Review Physiology

Management of Oxidative Stress: Crosstalk Between Brown/Beige Adipose Tissues and Skeletal Muscles

Ruping Pan, Yong Chen

Summary: Exercise plays a critical role in regulating oxidative metabolism, influencing ROS levels and mitigating oxidative stress. Proper exercise can help reduce ROS levels, especially in pathological conditions. Beige and brown adipose tissues are key players in this process, contributing to metabolic balance and protection against oxidative stress.

FRONTIERS IN PHYSIOLOGY (2021)

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Review Cell Biology

Ciliary control of adipocyte progenitor cell fate regulates energy storage

Sierra R. Scamfer, Mark D. Lee, Keren Hilgendorf

Summary: This review summarizes the role of the primary cilium in regulating the fate of adipocyte progenitor cells and highlights its importance in energy storage and adipose tissue function.

FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY (2022)

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Brown Fat as a Regulator of Systemic Metabolism beyond Thermogenesis

Okamatsu-Ogura Yuko, Masayuki Saito

Summary: The article provides an overview of brown adipose tissue (BAT), including its functions in health and diseases, the development of inducible thermogenic adipocytes (beige adipocytes), the diversity of thermogenic mechanisms, and BAT's influence on peripheral tissues and systemic homeostasis.

DIABETES & METABOLISM JOURNAL (2021)

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Maresin 1 activates brown adipose tissue and promotes browning of white adipose tissue in mice

Laura M. Laiglesia, Xavier Escote, Neira Sainz, Elisa Felix-Soriano, Eva Santamaria, Maria Collantes, Marta Fernandez-Galilea, Ignacio Colon-Mesa, Leyre Martinez-Fernandez, Tania Quesada-Lopez, Sergio Quesada-Vazquez, Carlos Rodriguez-Ortigosa, Jose M. Arbones-Mainar, Angela M. Valverde, J. Alfredo Martinez, Jesmond Dalli, Laura Herrero, Silvia Lorente-Cebrian, Francesc Villarroya, Maria J. Moreno-Aliaga

Summary: In this study, MaR1 is identified as a novel drug that promotes BAT activation and WAT browning by regulating thermogenic program in adipocytes and M2 polarization of macrophages.

MOLECULAR METABOLISM (2022)

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Review Plant Sciences

Stomatal cell fate commitment via transcriptional and epigenetic control: Timing is crucial

Eun-Deok Kim, Keiko U. Torii

Summary: The formation of stomata is a significant model system for understanding stem cell fate commitment. The regulatory strategies governing cell fate commitment differ between embryonic and postembryonic stomatal development. The interplay of transcription factors and cell cycle machineries is crucial for cell differentiation. Recent studies have provided insights into the molecular mechanisms underlying the interaction between transcription factors and epigenetic machineries.

PLANT CELL AND ENVIRONMENT (2023)

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Lipolysis regulates major transcriptional programs in brown adipocytes

Lasse K. Markussen, Elizabeth A. Rondini, Olivia Sveidahl Johansen, Jesper G. S. Madsen, Elahu G. Sustarsic, Ann-Britt Marcher, Jacob B. Hansen, Zachary Gerhart-Hines, James G. Granneman, Susanne Mandrup

Summary: This study uncovers the transcriptional network controlled by lipolysis in brown adipocytes and shows that lipolysis is required for the activation of the thermogenic gene program by beta-adrenergic signals. PPARs are identified as key mediators of lipolysis-induced activation of lipid metabolism and thermogenic genes. Additionally, lipolysis also activates the unfolded protein response and regulates the core circadian transcriptional machinery independently of PPARs.

NATURE COMMUNICATIONS (2022)

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Review Cell Biology

Human Brown Adipose Tissue and Metabolic Health: Potential for Therapeutic Avenues

Rajan Singh, Albert Barrios, Golnaz Dirakvand, Shehla Pervin

Summary: Obesity-related metabolic abnormalities affect over 650 million people globally, with various treatment approaches proving ineffective in reducing prevalence rates. Brown adipose tissue (BAT) may serve as a promising therapeutic target for obesity, enhancing energy expenditure and potentially reducing incidence of metabolic diseases.

CELLS (2021)

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Highly recruited brown adipose tissue does not in itself protect against obesity

Gabriella von Essen, Erik Lindsund, Elaina M. Maldonado, Petr Zouhar, Barbara Cannon, Jan Nedergaard

Summary: This study examines the possibility of countering obesity by activating brown or beige adipose tissue and UCP1. The findings show that although UCP1 protein may increase, it is not necessarily utilized for diet-induced thermogenesis. Constant activation of UCP1 is required to effectively ameliorate obesity development.

MOLECULAR METABOLISM (2023)

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Glutamine deficiency in solid tumor cells confers resistance to ribosomal RNA synthesis inhibitors

Melvin Pan, Christiane Zorbas, Maki Sugaya, Kensuke Ishiguro, Miki Kato, Miyuki Nishida, Hai-Feng Zhang, Marco M. Candeias, Akimitsu Okamoto, Takamasa Ishikawa, Tomoyoshi Soga, Hiroyuki Aburatani, Juro Sakai, Yoshihiro Matsumura, Tsutomu Suzuki, Christopher G. Proud, Denis L. J. Lafontaine, Tsuyoshi Osawa

Summary: Ribosome biogenesis is regulated by nutrient availability. Nutrient deprivation impairs pre-rRNA processing and leads to the accumulation of unprocessed rRNAs. Restoration of nutrients allows for the processing of stored pre-rRNAs and subsequent ribosome biogenesis. Failure to accumulate pre-rRNAs during nutrient stress disrupts ribosome assembly and activates p53-mediated apoptosis upon nutrient restoration.

NATURE COMMUNICATIONS (2022)

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Adipose Tissue Remodeling in Pathophysiology

Christopher Auger, Shingo Kajimura

Summary: Adipose tissue is not just an observer, but a complex endocrine organ and active participant in disease initiation and progression. Disruptions in biological processes within adipose can lead to metabolic disorders such as obesity and type 2 diabetes. Despite progress in understanding adipose tissue function and dysfunction, few diseases are treated by targeting maladaptation in adipose, which is often overlooked.

ANNUAL REVIEW OF PATHOLOGY-MECHANISMS OF DISEASE (2023)

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MYPT1-PP1β phosphatase negatively regulates both chromatin landscape and co-activator recruitment for beige adipogenesis

Hiroki Takahashi, Ge Yang, Takeshi Yoneshiro, Yohei Abe, Ryo Ito, Chaoran Yang, Junna Nakazono, Mayumi Okamoto-Katsuyama, Aoi Uchida, Makoto Arai, Hitomi Jin, Hyunmi Choi, Myagmar Tumenjargal, Shiyu Xie, Ji Zhang, Hina Sagae, Yanan Zhao, Rei Yamaguchi, Yu Nomura, Yuichi Shimizu, Kaito Yamada, Satoshi Yasuda, Hiroshi Kimura, Toshiya Tanaka, Youichiro Wada, Tatsuhiko Kodama, Hiroyuki Aburatani, Min-Sheng Zhu, Takeshi Inagaki, Timothy F. Osborne, Takeshi Kawamura, Yasushi Ishihama, Yoshihiro Matsumura, Juro Sakai

Summary: Protein kinase A promotes beige adipogenesis by phosphorylating proteins, including histone H3 lysine 9 demethylase JMJD1A. This process needs to be reversible and is regulated by MYPT1-PP1β phosphatase activity. This study uncovers regulatory cross-talk involved in beige adipogenesis that coordinates epigenetic regulation with direct activation of YAP/TAZ transcriptional co-activators.

NATURE COMMUNICATIONS (2022)

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Brown adipose tissue dysfunction promotes heart failure via a trimethylamine N-oxide-dependent mechanism

Yohko Yoshida, Ippei Shimizu, Atsuhiro Shimada, Keita Nakahara, Sachiko Yanagisawa, Minoru Kubo, Shinji Fukuda, Chiharu Ishii, Hiromitsu Yamamoto, Takamasa Ishikawa, Kuniyuki Kano, Junken Aoki, Goro Katsuumi, Masayoshi Suda, Kazuyuki Ozaki, Yutaka Yoshida, Shujiro Okuda, Shigeo Ohta, Shiki Okamoto, Yasuhiko Minokoshi, Kanako Oda, Toshikuni Sasaoka, Manabu Abe, Kenji Sakimura, Yoshiaki Kubota, Norihiko Yoshimura, Shingo Kajimura, Maria Zuriaga, Kenneth Walsh, Tomoyoshi Soga, Tohru Minamino

Summary: This study demonstrates that dysfunction of brown adipose tissue (BAT) is involved in the development of heart failure through choline metabolism disorientation. The research shows that BAT thermogenic capacity is reduced in mice with thoracic aortic constriction or myocardial infarction, leading to decreased body temperature. Moreover, hypoxia induces apoptosis of brown adipocytes. Enhancement of BAT function improves cardiac function, while genetic BAT dysfunction impairs systolic function.

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Lipolysis-derived linoleic acid drives beige fat progenitor cell proliferation

Ichitaro Abe, Yasuo Oguri, Anthony R. P. Verkerke, Lauar B. Monteiro, Carly M. Knuth, Christopher Auger, Yunping Qiu, Gregory P. Westcott, Saverio Cinti, Kosaku Shinoda, Marc G. Jeschke, Shingo Kajimura

Summary: Lipolysis-derived linoleic acid from adipose tissue can promote the proliferation of beige progenitor cells, leading to the formation of beige adipose tissue. Linoleic acid is oxidized in mitochondria and used for the synthesis of signaling molecules.

DEVELOPMENTAL CELL (2022)

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On the cutting edge: perspectives in bioenergetics

Melia Granath-Panelo, Anna Krook, Jared Rutter, Shingo Kajimura

Summary: The field of bioenergetics is expanding rapidly with new discoveries and potential therapeutic targets. The 2023 Keystone symposium on 'Bioenergetics in Health and Disease', jointly held with the symposium 'Adipose Tissue: Energizing Good Fat', featured a lineup of influential researchers who shared their insights.

NATURE REVIEWS ENDOCRINOLOGY (2023)

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Crucial role of iron in epigenetic rewriting during adipocyte differentiation mediated by JMJD1A and TET2 activity

Tomohiro Suzuki, Tetsuro Komatsu, Hiroshi Shibata, Akiko Tanioka, Diana Vargas, Reika Kawabata-Iwakawa, Fumihito Miura, Shinnosuke Masuda, Mayuko Hayashi, Kyoko Tanimura-Inagaki, Sumiyo Morita, Junki Kohmaru, Koji Adachi, Masayuki Tobo, Hideru Obinata, Tasuku Hirayama, Hiroshi Kimura, Juro Sakai, Hideko Nagasawa, Hideyuki Itabashi, Izuho Hatada, Takashi Ito, Takeshi Inagaki

Summary: Iron is essential for rewriting of epigenetic marks during adipocyte differentiation. Iron supply, mediated by lysosome-mediated ferritinophagy, plays a crucial role in the early stage of adipocyte differentiation. Iron deficiency during this period suppresses subsequent terminal differentiation and is associated with demethylation of repressive histone marks and DNA in the genomic regions of adipocyte differentiation-associated genes.

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The SLC25A47 locus controls gluconeogenesis and energy expenditure

Jin-Seon Yook, Zachary H. Taxin, Bo Yuan, Satoshi Oikawa, Christopher Auger, Beste Mutlu, Pere Puigserver, Sheng Hui, Shingo Kajimura

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Epitranscriptomics in metabolic disease

Yoshihiro Matsumura, Fan-Yan Wei, Juro Sakai

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Hypoxia activates SREBP2 through Golgi disassembly in bone marrow-derived monocytes for enhanced tumor growth

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Summary: Bone marrow-derived cells infiltrate hypoxic tumors and differentiate into mature macrophages, promoting pro-tumorigenic immunity. Activation of the transcription factor SREBP2, through Golgi disassembly and Golgi-ER fusion, regulates this differentiation process in a SCAP-independent manner.

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RANK ligand converts the NCoR/HDAC3 co-repressor to a PGC1(3-and RNA-dependent co-activator of osteoclast gene expression

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Summary: This study found that RANK signaling can convert the NCoR/HDAC3 co-repressor complex into a co-activator of AP-1 and NF-kB target genes, promoting mouse osteoclast differentiation. Mechanistically, RANK signaling activates the transcriptional co-activator PGC1(3 and inhibits HDAC3 activity for acetylated histone H3. Non-coding RNAs Dancr and Rnu12 play important roles in RANKL-induced osteoclast differentiation.

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Reply to Ren et al.: The role of a liver- specific mitochondrial carrier SLC25A47 in glucose homeostasis

Jin-Seon Yook, Zachary H. Taxin, Satoshi Oikawa, Masanori Fujimoto, Shingo Kajimura

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Chemogenetic activation of G(12) signaling enhances adipose tissue browning

Yuki Ono, Ryo Ito, Kaito Arai, Gurdeep Singh, Tsuyoshi Saitoh, Robert B. Russell, Francesco Raimondi, Junken Aoki, Juro Sakai, Asuka Inoue

SIGNAL TRANSDUCTION AND TARGETED THERAPY (2023)

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Environmental factor reversibly determines cellular identity through opposing Integrators that unify epigenetic and transcriptional pathways

Hiroki Takahashi, Ryo Ito, Yoshihiro Matsumura, Juro Sakai

Summary: Organisms must adapt to environmental stresses to ensure their survival and prosperity. Certain tissues demonstrate remarkable plasticity and adaptability, allowing reversible changes in cellular identity. Integrators sense environmental cues and coordinate the epigenetic and transcriptional processes required for these changes. Disruption of this coordination by adverse environmental factors contributes to disease development. Further research will reveal how organisms adapt to fluctuating environmental conditions by modifying cellular identities.

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T1R3 homomeric sweet taste receptor negatively regulates insulin-induced glucose transport through Gas-mediated microtubules disassembly in 3T3-L1 adipocytes

Yosuke Masubuchi, Jinhui Ma, Tomohiro Suzuki, Itaru Kojima, Takeshi Inagaki, Hiroshi Shibata

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ENDOCRINE JOURNAL (2022)

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Transcriptional and epigenetic control of brown and beige adipose cell fate and function (vol 17, pg 480, 2016)

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NATURE PUBLISHING GROUP

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