Sonia Kiran, Vijay Kumar, Santosh Kumar, Robert L Price, Udai P Singh
Obesity is characterized as a complex and multifactorial excess accretion of adipose tissue (AT) accompanied with alterations in the immune response that affects virtually all age and socioeconomic groups around the globe. The abnormal accumulation of AT leads to several metabolic diseases, including nonalcoholic fatty liver disorder (NAFLD), low-grade inflammation, type 2 diabetes mellitus (T2DM), cardiovascular disorders (CVDs), and cancer. AT is an endocrine organ composed of adipocytes and immune cells, including B-Cells, T-cells and macrophages...
April 24, 2021: Cells
Jie Cai, Gu Qiong, Chanjuan Li, Lulu Sun, Yuhong Luo, Shengheng Yuan, Frank J Gonzalez, Jun Xu
Saururus chinensis (S chinensis) has been used as an herb to treat edema, jaundice, and gonorrhea. Manassantin B (MNSB), a dineolignan isolated from S chinensis, was identified as a potent adipogenesis/lipogenesis inhibitor (IC50  = 9.3 nM). To explore the underlying mechanism, both adipogenesis and lipogenesis were measured in differentiated 3T3-L1 preadipocytes, murine primary preadipocytes and adipose tissue explants upon MNSB treatment. Key regulators of adipogenesis/lipogenesis were downregulated by MNSB treatment, mainly resulting from increased phosphorylation of AMPK which was identified as a vital regulator of adipogenesis and lipogenesis...
May 2021: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
Keiichi Ito, Marc Schneeberger, Alan Gerber, Miki Jishage, Francois Marchildon, Aarthi V Maganti, Paul Cohen, Jeffrey M Friedman, Robert G Roeder
The MED1 subunit has been shown to mediate ligand-dependent binding of the Mediator coactivator complex to multiple nuclear receptors, including the adipogenic PPARγ, and to play an essential role in ectopic PPARγ-induced adipogenesis of mouse embryonic fibroblasts. However, the precise roles of MED1, and its various domains, at various stages of adipogenesis and in adipose tissue have been unclear. Here, after establishing requirements for MED1, including specific domains, for differentiation of 3T3L1 cells and both primary white and brown preadipocytes, we used multiple genetic approaches to assess requirements for MED1 in adipocyte formation, maintenance, and function in mice...
April 22, 2021: Genes & Development
Subramani Manigandan, Sulagna Mukherjee, Jong Won Yun
Induction of white fat browning (beiging) and activation of brown fat has been considered a promising strategy to treat obesity and associated metabolic complications. However, the molecular mechanisms regulating brown and beige fat-mediated thermogenesis remains unclear. Our study aimed to identify genes with a hitherto unknown mechanism in the metabolic functions of adipocytes and identified family with sequence similarity 107, member A (FAM107A) as a factor that interferes with fat browning in white adipocytes...
April 17, 2021: Archives of Biochemistry and Biophysics
Célia Lopes, Eduardo Rocha, Inês L Pereira, Tânia V Madureira
Despite of physiological and toxicological relevance, the potential of androgens to influence fish lipid metabolism remains poorly explored. Here, brown trout primary hepatocytes were exposed to six concentrations (1 nM to 100 μM) of dihydrotestosterone (DHT) and testosterone (T), to assess changes in the mRNA levels of genes covering diverse lipid metabolic pathways. Acsl1, essential for fatty acid activation, was up-regulated by T and DHT, whereas the lipogenic enzymes FAS and ACC were up-regulated by the highest (100 μM) concentration of T and DHT, respectively...
March 26, 2021: Aquatic Toxicology
Shuwen Qian, Yan Tang, Qi-Qun Tang
Adipose tissues, including white, beige and brown adipose tissue, have evolved to be highly dynamic organs. Adipose tissues undergo profound changes during development and regeneration and readily undergo remodeling to meet the demands of an ever-changing metabolic landscape. The dynamics are determined by the high plasticity of adipose tissues, which contain various cell types: adipocytes, immune cells, endothelial cells, nerves and fibroblasts. There are numerous proteins that participate in regulating the plasticity of adipose tissues...
April 16, 2021: Journal of Biological Chemistry
Thomas Gantert, Fiona Henkel, Christine Wurmser, Josef Oeckl, Lena Fischer, Mark Haid, Jerzy Adamski, Julia Esser-von Bieren, Martin Klingenspor, Tobias Fromme
High uncoupling protein 1 (Ucp1) expression is a characteristic of differentiated brown adipocytes and is linked to adipogenic differentiation. Paracrine fibroblast growth factor 8b (FGF8b) strongly induces Ucp1 transcription in white adipocytes independent of adipogenesis. Here, we report that FGF8b and other paracrine FGFs act on brown and white preadipocytes to upregulate Ucp1 expression via a FGFR1-MEK1/2-ERK1/2 axis, independent of adipogenesis. Transcriptomic analysis revealed an upregulation of prostaglandin biosynthesis and glycolysis upon Fgf8b treatment of preadipocytes...
May 2021: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
Xueying Chen, Xiaoying He, Yan Guo, Liehua Liu, Hai Li, Jinfu Tan, Weidong Feng, Hongyu Guan, Xiaopei Cao, Haipeng Xiao, Yanbing Li
The adipocyte precursors (APs) located in white adipose tissue (WAT) are functionally significant in adipose plasticity and browning. Modifying adipogenesis or WAT browning targeted on APs is a promising mechanism for anti-obesity drug. We herein explored the in vitro actions and mechanisms of glucose-dependent insulinotropic polypeptide (GIP), a gut-derived peptide, in human adipose-derived mesenchymal stem cells (hADSCs) isolated from omentum. The hADSCs were cotreated with 100 nM GIP with or without equimolar concentration of GIP3-42 (a GIP receptor antagonist), and subsequently examined in vitro...
May 2021: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
Seung-Nam Kim, Dae Hee Kim, Hyuek Jong Lee, Joon Seo Lim, Ju-Hee Lee, Sung Yun Park, Young Jun Koh
Objectives: Ginsenoside Rg3 (Rg3), a main active component of Panax ginseng , has various therapeutic properties in literatures, and it has been studied for its potential use in obesity control due to its antiadipogenic effects in white adipocytes. However, little is known about its effects on brown adipocytes. Methods: The mechanisms through which Rg3 inhibits differentiation, adipogenesis, and ER stress-mediated cell death in mouse primary brown adipocytes (MPBAs) are explored...
2021: Evidence-based Complementary and Alternative Medicine: ECAM
Federica Scarano, Micaela Gliozzi, Maria Caterina Zito, Lorenza Guarnieri, Cristina Carresi, Roberta Macrì, Saverio Nucera, Miriam Scicchitano, Francesca Bosco, Stefano Ruga, Anna Rita Coppoletta, Rocco Mollace, Jessica Maiuolo, Irene Bava, Antonio Cardamone, Monica Ragusa, Ernesto Palma, Vincenzo Musolino, Vincenzo Mollace
The high incidence of obesity is associated with an increasing risk of several chronic diseases such as cardiovascular disease, type 2 diabetes and non-alcoholic fatty liver disease (NAFLD). Sustained obesity is characterized by a chronic and unsolved inflammation of adipose tissue, which leads to a greater expression of proinflammatory adipokines, excessive lipid storage and adipogenesis. The purpose of this review is to clarify how inflammatory mediators act during adipose tissue dysfunction in the development of insulin resistance and all obesity-associated diseases...
March 25, 2021: International Journal of Molecular Sciences
Lin Shuai, Bo-Han Li, Hao-Wen Jiang, Lin Yang, Jia Li, Jing-Ya Li
Brown and beige adipocytes are characterized as thermogenic adipocytes and have great potential for treating obesity and associated metabolic diseases. Here, we identify a conserved mammalian lysine 79 of histone H3 (H3K79) methyltransferase, disruptor of telomeric silencing -1 like (DOT1L), as a new epigenetic regulator that controls thermogenic adipocyte differentiation and function. We show that deletion of DOT1L in thermogenic adipocytes potently protects mice from diet-induced obesity, improves glucose homeostasis, alleviates hepatic steatosis, and facilitates adaptive thermogenesis in vivo Loss of DOT1L in primary preadipocytes significantly promotes brown and beige adipogenesis and thermogenesis in vitro Mechanistically, DOT1L epigenetically regulates the BAT-selective gene program through modulating H3K79 methylation, in particular H3K79me2 modification...
April 1, 2021: Diabetes
Yunqi Chao, Yonghui Jiang, Mianling Zhong, Kaiyan Wei, Chenxi Hu, Yifang Qin, Yiming Zuo, Lili Yang, Zheng Shen, Chaochun Zou
Alternative splicing (AS) regulates gene expression patterns at the post-transcriptional level and generates a striking expansion of coding capacities of genomes and cellular protein diversity. RNA splicing could undergo modulation and close interaction with genetic and epigenetic machinery. Notably, during the adipogenesis processes of white, brown and beige adipocytes, AS tightly interplays with the differentiation gene program networks. Here, we integrate the available findings on specific splicing events and distinct functions of different splicing regulators as examples to highlight the directive biological contribution of AS mechanism in adipogenesis and adipocyte biology...
April 1, 2021: Cell & Bioscience
Zhenzhen Wu, Jingyu Liu, Gang Chen, Junfeng Du, Huiyun Cai, Xuehui Chen, Gaoqi Ye, Yongting Luo, Yiyi Luo, Liwen Zhang, Hongxia Duan, Zheng Liu, Sai Yang, Hongwei Sun, Yan Cui, Lei Sun, Hongjie Zhang, Guizhi Shi, Taotao Wei, Pingsheng Liu, Xiyun Yan, Jing Feng, Pengcheng Bu
Obesity and its related complications pose an increasing threat to human health; however, targetable obesity-related membrane receptors are not yet elucidated. Here, the membrane receptor CD146 is demonstrated to play an essential role in obesity. In particular, CD146 acts as a new adipose receptor for angiopoietin-like protein 2 (ANGPTL2), which is thought to act on endothelial cells to activate adipose inflammation. ANGPTL2 binds to CD146 to activate cAMP response element-binding protein (CREB), which then upregulates CD146 during adipogenesis and adipose inflammation...
March 2021: Advanced Science (Weinheim, Baden-Wurttemberg, Germany)
Samantha M Logan, Kenneth B Storey
The thirteen-lined ground squirrel is a model fat-storing hibernator that nearly doubles its weight in the fall to fuel metabolism with triglycerides throughout the winter months. Hibernator brown and white adipose tissue (BAT, WAT) are important to study in terms of their inflammatory profile and tissue remodeling mechanisms since controlled and natural regulation of these processes could inform new pharmacological interventions that limit oxidative stress and inflammation in the adipose tissues of humans suffering from obesity, promote non-shivering thermogenesis-mediated weight loss, or prevent tissue damage in transplantable organs emerging from cold-storage...
March 9, 2021: Cellular Signalling
Yanli Miao, Haojie Qin, Yi Zhong, Kai Huang, Caijun Rao
Obesity is an increasingly serious epidemic worldwide characterized by an increase in the number and size of adipocytes. Adipose tissue maintains the balance between lipid storage and energy utilization. Therefore, adipose metabolism is of great significance for the prevention, treatment and intervention of obesity. Asprosin, a novel adipokine, is a circulating hormone mainly secreted by white adipose tissue. Previous studies have shown that asprosin plays a role in fasting-induced homeostasis, insulin resistance, and glucose tolerance...
March 1, 2021: Journal of Endocrinology
Yoon Hee Cho, Cheol Ryong Ku, Young-Suk Choi, Hyeon Jeong Lee, Eun Jig Lee
BACKGROUND: Danshen has been widely used in oriental medicine to improve body function. The purpose of this study is to investigate the effect of water-soluble Danshen extract (DE) on weight loss and on activation proteins involved in mitochondrial biogenesis in brown adipose tissue (BAT) in obese mice. METHODS: BAT was isolated from 7-week-old male Sprague-Dawley rats, and expression of proteins related to mitochondrial biogenesis was confirmed in both brown preadipocytes and mature brown adipocytes treated with DE...
February 2021: Endocrinology and Metabolism
Vitor Jacó Antraco, Bruna Kelly Sousa Hirata, Jussara de Jesus Simão, Maysa Mariana Cruz, Viviane Simões da Silva, Roberta Dourado Cavalcante da Cunha de Sá, Fernanda Miranda Abdala, Lucia Armelin-Correa, Maria Isabel Cardoso Alonso-Vale
The increasing impact of obesity on global human health intensifies the importance of studies focusing on agents interfering with the metabolism and remodeling not only of the white adipose tissue (WAT) but also of the liver. In the present study, we have addressed the impact of n-3 PUFA in adipose cells' proliferation and adipogenesis, as well as in the hepatic lipid profile and morphology. Mice were induced to obesity by the consumption of a high-fat diet (HFD) for 16 weeks. At the 9th week, the treatment with fish oil (FO) was initiated and maintained until the end of the period...
February 15, 2021: Nutrients
Girolamo Di Maio, Nicola Alessio, Ibrahim Halil Demirsoy, Gianfranco Peluso, Silverio Perrotta, Marcellino Monda, Giovanni Di Bernardo
Brown-like adipocytes can be induced in white fat depots by a different environmental or drug stimuli, known as "browning" or "beiging". These brite adipocytes express thermogenin UCP1 protein and show different metabolic advantages, such as the ability to acquire a thermogenic phenotype corresponding to standard brown adipocytes that counteracts obesity. In this research, we evaluated the effects of several browning agents during white adipocyte differentiation of bone marrow-derived mesenchymal stromal cells (MSCs)...
February 16, 2021: Cells
Hailuan Zeng, Weihong Sun, Xinping Ren, Nan Xia, Sheng Zheng, Haixia Xu, Yan Tian, Xianghui Fu, Jingyan Tian
BACKGROUND: MicroRNA-26a (miR-26a) is a key player in tumor suppression and plays important roles in glucose and lipid metabolism. However, its function in adipose tissue is not well defined. OBJECTIVE: The study aimed to examine the effect on fat expansion and function of miR-26a in adipose tissue. METHODS: Adipose-specific miR-26a transgenic mice (Ap2-miR-26a) were firstly generated by breeding miR-26a floxed (Mir26a loxP /loxP ) mice with Ap2-Cre recombinase transgenic mice...
March 2, 2021: Molecular and Cellular Endocrinology
Yukimasa Takeda, Toshikazu Yoshikawa, Ping Dai
Brown adipogenesis contributes to controlling systemic energy balance by enhancing glucose and lipid consumptions. We have previously reported chemical compound-induced brown adipocytes (ciBAs) directly converted from human dermal fibroblasts using a serum-free medium. In this study, genome-wide transcriptional analysis was performed in ciBAs in comparison with the control fibroblasts. A broad range of integrated gene expression was enhanced in functional groups including tricarboxylic acid cycle, electron transfer chain, triglycerides metabolism, fatty acid and glucose metabolism, and adaptive thermogenesis...
March 3, 2021: Scientific Reports
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