Article
Multidisciplinary Sciences
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)
Review
Endocrinology & Metabolism
Yasuhiro Onogi, Siegfried Ussar
Summary: Brown adipose tissue (BAT) is a tightly controlled regulator of body temperature and nutrient balance, influenced by complex hormonal and nervous inputs. This article provides an overview of key regulatory circuits, including diurnal rhythms and the interdependency of nutrient utilization in thermogenesis. It also discusses additional factors mediating sympathetic BAT activation and limitations of glucose-based BAT activity measurements.
TRENDS IN ENDOCRINOLOGY AND METABOLISM
(2022)
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
Endocrinology & Metabolism
Jiefu Wang, Yasuhiro Onogi, Martin Krueger, Josef Oeckl, Ruth Karlina, Inderjeet Singh, Stefanie M. Hauck, Regina Feederle, Yongguo Li, Siegfried Ussar
Summary: PAT2 serves as an important sensor of extracellular amino acids and regulates lysosomal acidification in brown adipocytes. Loss or overexpression of PAT2 affects lysosomal acidification and starvation-induced S6K re-phosphorylation, as PAT2 facilitates the assembly of lysosomal vATPase by recruiting the cytoplasmic V1 subunit to the lysosome.
MOLECULAR METABOLISM
(2022)
Article
Multidisciplinary Sciences
Jungin Kwon, Yu-Sheng Yeh, Satoko Kawarasaki, Hiroto Minamino, Yoshihito Fujita, Yuko Okamatsu-Ogura, Haruya Takahashi, Wataru Nomura, Shigenobu Matsumura, Rina Yu, Kazuhiro Kimura, Masayuki Saito, Nobuya Inagaki, Kazuo Inoue, Teruo Kawada, Tsuyoshi Goto
Summary: This study demonstrates the role of the mevalonate (MVA) biosynthesis pathway in regulating brown adipocyte development and survival. Inhibiting the rate-limiting enzyme in the MVA pathway, 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR), suppresses brown adipocyte differentiation and leads to apoptosis of mature brown adipocytes. The study reveals that geranylgeranyl pyrophosphate (GGPP) generated from the MVA pathway is essential for brown adipocyte development and survival.
Article
Cell Biology
Shraboni Ghosh, Joseph F. Nelson, Geoffrey M. C. Cobb, J. Peter Etchells, Miguel de Lucas
Summary: The balance between cell proliferation and differentiation in the cambium determines the formation of plant vascular tissues. This study reveals that the activity of PIF transcription factors, regulated by light, modulates TDIF signaling and vascular cell differentiation. This research uncovers the molecular mechanism that connects light perception to vascular differentiation in plants.
Article
Endocrinology & Metabolism
Yuko Nabatame, Tetsuya Hosooka, Chikako Aoki, Yusei Hosokawa, Makoto Imamori, Yoshikazu Tamori, Yuko Okamatsu-Ogura, Takeshi Yoneshiro, Shingo Kajimura, Masayuki Saito, Wataru Ogawa
Summary: The study highlights the importance of KLF15 in regulating fuel switching between glucose and fatty acids in brown adipose tissue. This is achieved through its impact on fatty acid and glucose oxidation, as well as pyruvate dehydrogenase complex activity in BAT.
JOURNAL OF DIABETES INVESTIGATION
(2021)
Article
Biochemistry & Molecular Biology
Huong Giang Pham, Sulagna Mukherjee, Min Ji Choi, Jong Won Yun
Summary: This study demonstrates the important roles of BMP11 in white and brown adipocytes, showing that silencing of Bmp11 affects the expression of specific genes and reduces the levels of lipolytic protein markers. Moreover, BMP11 induces browning of 3T3-L1 adipocytes by coordinating multiple signaling pathways, including mTORC1-COX2 and p38MAPK-PGC-1 alpha as non-canonical pathways, as well as Smad1/5/8 as a canonical pathway. These results suggest the therapeutic potential of BMP11 for obesity treatment.
CELL BIOCHEMISTRY AND FUNCTION
(2021)
Article
Biochemistry & Molecular Biology
Shihe Zhang, Pengkang Song, Xiaoyou Chen, Yu Wang, Xuyang Gao, Lin Liang, Junxing Zhao
Summary: APS promotes differentiation of brown adipocytes in C3H10T 1/2 cells by targeting Prdm16 through miRNA-6911, leading to improved insulin sensitivity and increased expression of brown adipogenic marker proteins.
Article
Multidisciplinary Sciences
Ran Song, William McAlpine, Aaron M. Fond, Evan Nair-Gill, Jin Huk Choi, Elisabeth E. L. Nystroem, Liisa Arike, Sydney Field, Xiaohong Li, Jeffrey A. SoRelle, James J. Moresco, Eva Marie Y. Moresco, John R. Yates, Parastoo Azadi, Josephine Ni, George M. H. Birchenough, Bruce Beutler, Emre E. Turer
Summary: The dynamic intestinal barrier is important for intestinal immunity by separating the host from microbiota. The mutation in TVP23B leads to susceptibility to colitis. TVP23B controls Paneth cells and goblet cells, affecting antimicrobial peptides and mucus layer permeability.
NATURE COMMUNICATIONS
(2023)
Article
Biochemistry & Molecular Biology
Maria A. Ahonen, Marcus Horing, Van Dien Nguyen, Sami Qadri, Juuso H. Taskinen, Meghana Nagaraj, Martin Wabitsch, Pamela Fischer-Posovszky, You Zhou, Gerhard Liebisch, P. A. Nidhina Haridas, Hannele Yki-Jarvinen, Vesa M. Olkkonen
Summary: This study found that thyroid hormone responsive protein (THRSP) is regulated by insulin in human adipose tissue and adipocytes. Insulin resistance leads to downregulation of THRSP expression. Silencing of THRSP results in impaired mitochondrial function and disrupted lipid metabolism.
MOLECULAR MEDICINE
(2022)
Article
Biochemistry & Molecular Biology
Jinchun Chang, Chenjia Guo, Jianyu Li, Zhangqian Liang, Yankai Wang, Anliang Yu, Runze Liu, Yuting Guo, Jian Chen, Song Huang
Summary: The study found that EN1 is highly expressed in glioma cells and tissues, and its increased expression level is associated with poor prognosis. EN1 influences glioma cell proliferation, migration, and sensitivity to radiation by regulating Gli1 levels and the primary cilia-related protein TULP3. These findings suggest that EN1 plays an oncogenic role in glioblastoma pathogenesis.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Endocrinology & Metabolism
Jee Hyung Sohn, Yul Ji, Chang-Yun Cho, Hahn Nahmgoong, Sangsoo Lim, Yong Geun Jeon, Sang Mun Han, Ji Seul Han, Isaac Park, Hyun-Woo Rhee, Sun Kim, Jae Bum Kim
Summary: The study showed that a defect in G6PD in brown adipocytes leads to cytosolic ROS accumulation, impairing thermogenic function. Administration of antioxidants or ERK inhibition can restore thermogenic activity.
Article
Thermodynamics
Shijing Luo, Yifei Wang, Wending Pana, Xiaolong Zhao, Kee Wah Leong, Dennis Y. C. Leung
Summary: A microfluidic fuel cell (MFC) with an alkaline anolyte and acidic catholyte co-flow configuration is designed to achieve high open-circuit voltage and power density. Gelling polymers are added to increase the density and viscosity of the electrolytes, reducing the required flow rate. This design not only resolves the trade-off between performance and fuel utilization, but also significantly improves peak power density and fuel utilization.
ENERGY CONVERSION AND MANAGEMENT
(2023)
Article
Physiology
Bahetiyaer Huwatibieke, Wenzhen Yin, Lingchao Liu, Yuxin Jin, Xinxin Xiang, Jingyan Han, Weizhen Zhang, Yin Li
Summary: The study demonstrates that the mTOR signaling pathway affects the transformation of adipocytes by regulating mitochondrial quality control in brown adipocytes. Activation of mTOR signaling inhibits the mitochondrial quality control and promotes the transformation from brown to white adipocytes, while inhibition of mTOR signaling enhances mitochondrial quality control and inhibits the phenotypic shift.
FRONTIERS IN PHYSIOLOGY
(2021)
Editorial Material
Endocrinology & Metabolism
Yu-Hua Tseng
Summary: Several exciting discoveries in 2022 shed light on the cellular composition and cell-cell communication within the adipose tissue, as well as its interaction with other organs and its role in metabolism.
NATURE REVIEWS ENDOCRINOLOGY
(2023)
Article
Endocrinology & Metabolism
Hamza Mechchate, Abdualrahman Mohammed Abdualkader, James Bradshaw Bernacchi, Keshav Gopal, S. Amirhossein Tabatabaei Dakhili, Kunyan Yang, Amanda A. Greenwell, Xingxing Kong, Peter A. Crawford, Rami Al Batran
Summary: Muscle ketone body oxidation does not affect glucose and fat metabolism, but disrupts muscle BCAA catabolism and alters BCATm expression.
AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM
(2023)
Article
Pharmacology & Pharmacy
Christina T. Saed, Seyed Amirhossein Tabatabaei Dakhili, Amanda A. Greenwell, Jordan S. F. Chan, Kunyan Yang, Keshav Gopal, Farah Eaton, Rami Al Batran, John R. Ussher
Summary: Recent studies have shown that stimulating the rate-limiting enzyme of glucose oxidation, pyruvate dehydrogenase (PDH), can reverse obesity-induced non-alcoholic fatty liver disease (NAFLD), and this can be achieved with the use of the antianginal drug ranolazine. The aim of this study was to determine if ranolazine's effects on NAFLD and hyperglycaemia require increased hepatic PDH activity.
BASIC & CLINICAL PHARMACOLOGY & TOXICOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Sunday Amos Onikanni, Cheng-Ying Yang, Lloyd Noriega, Chih-Hao Wang
Summary: In recent years, thermogenic differentiation and activation in brown and white adipose tissues have been considered as a promising strategy for treating and improving obesity. However, the pharmacological approach to this process has been limited, posing a challenge for obesity treatment. This research examines the effects of U0126 compound on thermogenic differentiation during adipogenesis and suggests it as a potential pharmacological option to enhance thermogenic adipocyte formation and energy expenditure.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Multidisciplinary Sciences
Tadataka Tsuji, Yang Zhang, Yu-Hua Tseng
Summary: This article describes a rapid and efficient method for knocking out a gene of interest in brown adipose tissue (BAT) using a combined Cre-LoxP, CRISPR-Cas9, and adeno-associated virus (AAV) single-guide RNA (sgRNA) system. This method can be broadly applied to study the biological functions of genes in BAT.
JOVE-JOURNAL OF VISUALIZED EXPERIMENTS
(2023)
Article
Cell Biology
Seyed Amirhossein Tabatabaei Dakhili, Kunyan Yang, Cassandra A. A. Locatelli, Christina T. Saed, Amanda A. Greenwell, Jordan S. F. Chan, Jadin J. Chahade, Jared Scharff, Shahad Al-Imarah, Farah Eaton, Peter A. Crawford, Keshav Gopal, Erin E. Mulvihill, John R. Ussher
Summary: Acute elevations in circulating ketones improve glucose tolerance in obesity, independent of muscle ketone oxidation.
AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY
(2023)
Article
Cell Biology
Tadataka Tsuji, Yu-Hua Tseng
Summary: Adipose tissue is important for metabolism regulation, producing bioactive molecules that communicate with and modulate other organs. Lipid metabolites, or lipokines, have been found to play a key role in various metabolic processes. This review discusses the latest advances in adipose tissue-derived lipokines and their cellular and molecular functions, as well as potential therapeutic implications for obesity and its associated complications.
CURRENT OPINION IN GENETICS & DEVELOPMENT
(2023)
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
Genetics & Heredity
Matthew D. Lynes, Qian Huang, Carolina Cora, Sheng-Chiang Su, Peng Yi, Yu-Hua Tseng
Summary: This study reveals the complexity of genetic regulation of brown adipogenesis and glucose metabolism. The E3-ubiquitin ligase Rfwd2 was found to suppress glucose uptake in brown adipocytes.
Article
Endocrinology & Metabolism
Kanako Iwasaki, Benjamin Lalani, Jiho Kahng, Priscila Carapeto, Stephanie Sanjines, Francesko Hela, Cristian Abarca, Tadataka Tsuji, Justin Darcy, Andrzej Bartke, Yu-Hua Tseng, Rohit N. N. Kulkarni, Cristina Aguayo-Mazzucato
Summary: The IGF1R signaling pathway plays a crucial role in age-induced dysfunction and senescence of beta-cells. Understanding the interaction between senescence and aging can provide insights into the development of interventions to restore beta-cell function and prevent progression to type 2 diabetes (T2D).
FRONTIERS IN ENDOCRINOLOGY
(2023)
Article
Biology
Farnaz Shamsi, Rongbin Zheng, Li-Lun Ho, Kaifu Chen, Yu-Hua Tseng
Summary: Brown adipose tissue (BAT) regulates body temperature through thermogenesis. Cold exposure enhances intercellular interactions among major cell types in BAT, leading to remodeling of the extracellular matrix, inflammatory response, angiogenesis, and neurite growth.
COMMUNICATIONS BIOLOGY
(2023)
Article
Medicine, Research & Experimental
Hirofumi Nagao, Weikang Cai, Bruna B. Brandao, Nicolai J. Wewer Albrechtsen, Martin Steger, Arijeet K. Gattu, Hui Pan, Jonathan M. Dreyfuss, F. Thomas Wunderlich, Matthias Mann, C. Ronald Kahn
Summary: Insulin and IGF-1 receptors have similar signaling systems but different physiological roles. Replacement of leucine-973 in the intracellular juxtamembrane region with phenylalanine resulted in altered signaling, decreased insulin sensitivity, increased cell growth, and impaired receptor internalization. This amino acid residue plays a crucial role in differentiating the signaling of IR and IGF1R.
JOURNAL OF CLINICAL INVESTIGATION
(2023)
Article
Endocrinology & Metabolism
Satoru Sugimoto, Hebe Agustina Mena, Brian E. Sansbury, Shio Kobayashi, Tadataka Tsuji, Chih-Hao Wang, Xuanzhi Yin, Tian Lian Huang, Joji Kusuyama, Sean D. Kodani, Justin Darcy, Gerson Profeta, Nayara Pereira, Rudolph E. Tanzi, Can Zhang, Thomas Serwold, Efi Kokkotou, Laurie J. Goodyear, Aaron M. Cypess, Luiz Osorio Leiria, Matthew Spite, Yu-Hua Tseng
Summary: The study found that cold exposure can improve obesity-induced inflammation and insulin resistance, and enhance glucose tolerance. The beneficial effects are dependent on brown adipose tissue (BAT) and liver. The researchers discovered that cold and beta 3-adrenergic stimulation promote the production of MaR2 from BAT, which reduces inflammation in obesity, particularly targeting macrophages in the liver.