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Brown adipocyte

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https://www.readbyqxmd.com/read/29035280/adipocyte-cannabinoid-receptor-cb1-regulates-energy-homeostasis-and-alternatively-activated-macrophages
#1
Inigo Ruiz de Azua, Giacomo Mancini, Raj Kamal Srivastava, Alejandro Aparisi Rey, Pierre Cardinal, Laura Tedesco, Cristina Maria Zingaretti, Antonia Sassmann, Carmelo Quarta, Claudia Schwitter, Andrea Conrad, Nina Wettschureck, V Kiran Vemuri, Alexandros Makriyannis, Jens Hartwig, Maria Mendez-Lago, Laura Bindila, Krisztina Monory, Antonio Giordano, Saverio Cinti, Giovanni Marsicano, Stefan Offermanns, Enzo Nisoli, Uberto Pagotto, Daniela Cota, Beat Lutz
Dysregulated adipocyte physiology leads to imbalanced energy storage, obesity, and associated diseases, imposing a costly burden on current health care. Cannabinoid receptor type-1 (CB1) plays a crucial role in controlling energy metabolism through central and peripheral mechanisms. In this work, adipocyte-specific inducible deletion of the CB1 gene (Ati-CB1-KO) was sufficient to protect adult mice from diet-induced obesity and associated metabolic alterations and to reverse the phenotype in already obese mice...
October 16, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/29033835/farnesol-has-an-anti-obesity-effect-in-high-fat-diet-induced-obese-mice-and-induces-the-development-of-beige-adipocytes-in-human-adipose-tissue-derived-mesenchymal-stem-cells
#2
Hye-Lin Kim, Yunu Jung, Jinbong Park, Dong-Hyun Youn, JongWook Kang, Seona Lim, Beom Su Lee, Mi-Young Jeong, Seong-Kyu Choe, Raekil Park, Kwang Seok Ahn, Jae-Young Um
Brown adipocytes dissipate energy as heat and hence have an important therapeutic capacity for obesity. Development of brown-like adipocytes (also called beige) is also another attractive target for obesity treatment. Here, we investigated the effect of farnesol, an isoprenoid, on adipogenesis in adipocytes and on the browning of white adipose tissue (WAT) as well as on the weight gain of high-fat diet (HFD)-induced obese mice. Farnesol inhibited adipogenesis and the related key regulators including peroxisome proliferator-activated receptor γ (PPARγ) and CCAAT/enhancer binding protein α through the up-regulation of AMP-activated protein kinase in 3T3-L1 murine adipocytes and human adipose tissue-derived mesenchymal stem cells (hAMSCs)...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/29032027/peripheral-neuropathy-and-hindlimb-paralysis-in-a-mouse-model-of-adipocyte-specific-knockout-of-lkb1
#3
Yan Xiong, Jessica C Page, Naagarajan Narayanan, Chao Wang, Zhihao Jia, Feng Yue, Xine Shi, Wen Jin, Keping Hu, Meng Deng, Riyi Shi, Tizhong Shan, Gongshe Yang, Shihuan Kuang
Brown adipose tissues (BAT) burn lipids to generate heat through uncoupled respiration, thus representing a powerful target to counteract lipid accumulation and obesity. The tumor suppressor liver kinase b1 (Lkb1) is a key regulator of cellular energy metabolism; and adipocyte-specific knockout of Lkb1 (Ad-Lkb1 KO) leads to the expansion of BAT, improvements in systemic metabolism and resistance to obesity in young mice. Here we report the unexpected finding that the Ad-Lkb1 KO mice develop hindlimb paralysis at mid-age...
September 21, 2017: EBioMedicine
https://www.readbyqxmd.com/read/29031721/cdkal1-a-type-2-diabetes-susceptibility-gene-regulates-mitochondrial-function-in-adipose-tissue
#4
Colin J Palmer, Raphael J Bruckner, Joao A Paulo, Lawrence Kazak, Jonathan Z Long, Amir I Mina, Zhaoming Deng, Katherine B LeClair, Jessica A Hall, Shangyu Hong, Peter-James H Zushin, Kyle L Smith, Steven P Gygi, Susan Hagen, David E Cohen, Alexander S Banks
OBJECTIVES: Understanding how loci identified by genome wide association studies (GWAS) contribute to pathogenesis requires new mechanistic insights. Variants within CDKAL1 are strongly linked to an increased risk of developing type 2 diabetes and obesity. Investigations in mouse models have focused on the function of Cdkal1 as a tRNA(Lys) modifier and downstream effects of Cdkal1 loss on pro-insulin translational fidelity in pancreatic β-cells. However, Cdkal1 is broadly expressed in other metabolically relevant tissues, including adipose tissue...
October 2017: Molecular Metabolism
https://www.readbyqxmd.com/read/29031720/brown-adipocytes-can-display-a-mammary-basal-myoepithelial-cell-phenotype-in%C3%A2-vivo
#5
Li Li, Baoguo Li, Min Li, Chaoqun Niu, Guanlin Wang, Ting Li, Elżbieta Król, Wanzhu Jin, John R Speakman
OBJECTIVE: Previous work has suggested that white adipocytes may also show a mammary luminal secretory cell phenotype during lactation. The capacity of brown and beige/brite adipocytes to display a mammary cell phenotype and the levels at which they demonstrate such phenotypes in vivo is currently unknown. METHODS: To investigate the putative adipocyte origin of mammary gland cells, we performed genetic lineage-labeling experiments in BAT and the mammary glands...
October 2017: Molecular Metabolism
https://www.readbyqxmd.com/read/29031716/adipocyte-glucocorticoid-receptor-is-important-in-lipolysis-and-insulin-resistance-due-to-exogenous-steroids-but-not-insulin-resistance-caused-by-high-fat-feeding
#6
Yachen Shen, Hyun Cheol Roh, Manju Kumari, Evan D Rosen
OBJECTIVE: The critical role of adipose tissue in energy and nutrient homeostasis is influenced by many external factors, including overnutrition, inflammation, and exogenous hormones. Prior studies have suggested that glucocorticoids (GCs) in particular are major drivers of physiological and pathophysiological changes in adipocytes. In order to determine whether these effects directly require the glucocorticoid receptor (GR) within adipocytes, we generated adipocyte-specific GR knockout (AGRKO) mice...
October 2017: Molecular Metabolism
https://www.readbyqxmd.com/read/29026134/mct1-and-mct4-expression-and-lactate-flux-activity-increase-during-white-and-brown-adipogenesis-and-impact-adipocyte-metabolism
#7
Charlotte Petersen, Mette D Nielsen, Elise S Andersen, Astrid L Basse, Marie S Isidor, Lasse K Markussen, Birgitte M Viuff, Ian H Lambert, Jacob B Hansen, Stine F Pedersen
Adipose tissue takes up glucose and releases lactate, thereby contributing significantly to systemic glucose and lactate homeostasis. This implies the necessity of upregulation of net acid and lactate flux capacity during adipocyte differentiation and function. However, the regulation of lactate- and acid/base transporters in adipocytes is poorly understood. Here, we tested the hypothesis that adipocyte thermogenesis, browning and differentiation are associated with an upregulation of plasma membrane lactate and acid/base transport capacity that in turn is important for adipocyte metabolism...
October 12, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29021914/retinoic-acid-induces-white-adipose-tissue-browning-by-increasing-adipose-vascularity-and-inducing-beige-adipogenesis-of-pdgfr%C3%AE-adipose-progenitors
#8
Bo Wang, Xing Fu, Xingwei Liang, Jeanene M Deavila, Zhixiu Wang, Liang Zhao, Qiyu Tian, Junxing Zhao, Noe Alberto Gomez, Sophie C Trombetta, Mei-Jun Zhu, Min Du
Formation of beige adipocytes within white adipose tissue enhances energy expenditure, which is a promising strategy to reduce obesity and prevent metabolic symptoms. Vitamin A and its bioactive metabolite, retinoic acid (RA), have regulatory roles in lipid metabolism. Here we report that RA induces white adipose tissue browning via activating vascular endothelial growth factor (VEGF) signaling. RA triggered angiogenesis and elicited de novo generation of platelet-derived growth factor receptor α positive (PDGFRα(+)) adipose precursor cells via VEGFA/VEGFR2 signaling...
2017: Cell Discovery
https://www.readbyqxmd.com/read/29021624/mkk6-controls-t3-mediated-browning-of-white-adipose-tissue
#9
Nuria Matesanz, Edgar Bernardo, Rebeca Acín-Pérez, Elisa Manieri, Sonia Pérez-Sieira, Lourdes Hernández-Cosido, Valle Montalvo-Romeral, Alfonso Mora, Elena Rodríguez, Luis Leiva-Vega, Ana Victoria Lechuga-Vieco, Jesús Ruiz-Cabello, Jorge L Torres, Maria Crespo-Ruiz, Francisco Centeno, Clara V Álvarez, Miguel Marcos, Jose Antonio Enríquez, Ruben Nogueiras, Guadalupe Sabio
Increasing the thermogenic capacity of adipose tissue to enhance organismal energy expenditure is considered a promising therapeutic strategy to combat obesity. Here, we report that expression of the p38 MAPK activator MKK6 is elevated in white adipose tissue of obese individuals. Using knockout animals and shRNA, we show that Mkk6 deletion increases energy expenditure and thermogenic capacity of white adipose tissue, protecting mice against diet-induced obesity and the development of diabetes. Deletion of Mkk6 increases T3-stimulated UCP1 expression in adipocytes, thereby increasing their thermogenic capacity...
October 11, 2017: Nature Communications
https://www.readbyqxmd.com/read/29021616/the-thermogenic-actions-of-natriuretic-peptide-in-brown-adipocytes-the-direct-measurement-of-the-intracellular-temperature-using-a-fluorescent-thermoprobe
#10
Haruka Kimura, Tomohisa Nagoshi, Akira Yoshii, Yusuke Kashiwagi, Yoshiro Tanaka, Keiichi Ito, Takuya Yoshino, Toshikazu D Tanaka, Michihiro Yoshimura
In addition to the various effects of natriuretic peptides (NPs) on cardiovascular systems, increasing attention is being paid to the possibility that NPs induce adipose tissue browning and activate thermogenic program. We herein established a direct intracellular temperature measurement system using a fluorescent thermoprobe and investigated the thermogenic effects of A-type NP (ANP) on brown adipocytes. The thermoprobe was successfully introduced into rat brown adipocytes, and the temperature dependent change in fluorescence intensity ratio was measured using a fluorescence microscope...
October 11, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29018208/difference-in-intracellular-temperature-rise-between-matured-and-precursor-brown-adipocytes-in-response-to-uncoupler-and-%C3%AE-adrenergic-agonist-stimuli
#11
Toshikazu Tsuji, Kumiko Ikado, Hideki Koizumi, Seiichi Uchiyama, Kazuaki Kajimoto
Brown adipocytes function to maintain body temperature by heat production. However, direct measurement of heat production at a single cell level remains difficult. Here we developed a method to measure the temperature within primary cultured brown adipocytes using a cationic fluorescent polymeric thermometer. Placement of the thermometer within a matured brown adipocyte and a precursor cell enabled the detection of heat production following uncoupler treatment. The increase in the intracellular temperature due to stimulation with a mitochondrial uncoupler was higher in matured brown adipocytes than in precursor cells...
October 10, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28994031/differential-adipose-tissue-proteomics
#12
Kelly J Shields, Changgong Wu
Differential proteomic analysis (comparative quantitative proteomics) is a robust quantitative technique used to detect and identify the proteome of selected tissues. The expression levels (upregulated vs. downregulated) of proteins in tissue samples that differ by experimental design or anatomic location are determined by a series of assays including (1) 2D difference gel electrophoresis (2D-DiGE), (2) protein spot picking based on a priori thresholds, (3) Mass Spectrometry, and (4) follow-up Western Blot for antibody validation (Chen et al...
October 10, 2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28990936/olfactory-receptor-544-reduces-adiposity-by-steering-fuel-preference-toward-fats
#13
Chunyan Wu, Su Hyeon Hwang, Yaoyao Jia, Joobong Choi, Yeon-Ji Kim, Dahee Choi, Duleepa Pathiraja, In-Geol Choi, Seung-Hoi Koo, Sung-Joon Lee
Olfactory receptors (ORs) are present in tissues outside the olfactory system; however, the function of these receptors remains relatively unknown. Here, we determined that olfactory receptor 544 (Olfr544) is highly expressed in the liver and adipose tissue of mice and regulates cellular energy metabolism and obesity. Azelaic acid (AzA), an Olfr544 ligand, specifically induced PKA-dependent lipolysis in adipocytes and promoted fatty acid oxidation (FAO) and ketogenesis in liver, thus shifting the fuel preference to fats...
October 9, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28988979/irx3-promotes-the-browning-of-white-adipocytes-and-its-rare-variants-are-associated-with-human-obesity-risk
#14
Yaoyu Zou, Peng Lu, Juan Shi, Wen Liu, Minglan Yang, Shaoqian Zhao, Na Chen, Maopei Chen, Yingkai Sun, Aibo Gao, Qingbo Chen, Zhiguo Zhang, Qinyun Ma, Tinglu Ning, Xiayang Ying, Jiabin Jin, Xiaxing Deng, Baiyong Shen, Yifei Zhang, Bo Yuan, Sophie Kauderer, Simin Liu, Jie Hong, Ruixin Liu, Guang Ning, Weiqing Wang, Weiqiong Gu, Jiqiu Wang
BACKGROUND: IRX3 was recently reported as the effector of the FTO variants. We aimed to test IRX3's roles in the browning program and to evaluate the association between the genetic variants in IRX3 and human obesity. METHODS: IRX3 expression was examined in beige adipocytes in human and mouse models, and further validated in induced beige adipocytes. The browning capacity of primary preadipocytes was assessed with IRX3 knockdown. Luciferase reporter analysis and ChIP assay were applied to investigate IRX3's effects on UCP1 transcriptional activity...
September 13, 2017: EBioMedicine
https://www.readbyqxmd.com/read/28988965/do-estrogens-enhance-activation-of-brown-and-beiging-of-adipose-tissues
#15
Aaron P Frank, Biff F Palmer, Deborah J Clegg
Obesity and its associated co-morbidities are worldwide public health concerns. Obesity is characterized by excessive adipose tissue accumulation; however, it is important to recognize that human and rodent adipose tissues are made up of several distinct adipose tissue sub-types. White adipose tissue (WAT) is considered the prototypical fat cell, due to its capacity and capability to store large amounts of lipid. In contrast, brown adipose tissue (BAT) oxidizes substrates to generate heat. BAT contains more mitochondria than WAT and express uncoupling protein-1 (UCP1), which mediates BAT thermogenesis...
October 5, 2017: Physiology & Behavior
https://www.readbyqxmd.com/read/28988822/lipolysis-in-brown-adipocytes-is-not-essential-for-cold-induced-thermogenesis-in-mice
#16
Hyunsu Shin, Yinyan Ma, Tatyana Chanturiya, Qiang Cao, Youlin Wang, Anil K G Kadegowda, Rachel Jackson, Dominic Rumore, Bingzhong Xue, Hang Shi, Oksana Gavrilova, Liqing Yu
Lipid droplet (LD) lipolysis in brown adipose tissue (BAT) is generally considered to be required for cold-induced nonshivering thermogenesis. Here, we show that mice lacking BAT Comparative Gene Identification-58 (CGI-58), a lipolytic activator essential for the stimulated LD lipolysis, have normal thermogenic capacity and are not cold sensitive. Relative to littermate controls, these animals had higher body temperatures when they were provided food during cold exposure. The increase in body temperature in the fed, cold-exposed knockout mice was associated with increased energy expenditure and with increased sympathetic innervation and browning of white adipose tissue (WAT)...
October 5, 2017: Cell Metabolism
https://www.readbyqxmd.com/read/28988768/crosstalk-between-kcnk3-mediated-ion-current-and-adrenergic-signaling-regulates-adipose-thermogenesis-and-obesity
#17
Yi Chen, Xing Zeng, Xuan Huang, Sara Serag, Clifford J Woolf, Bruce M Spiegelman
Adrenergic stimulation promotes lipid mobilization and oxidation in brown and beige adipocytes, where the harnessed energy is dissipated as heat in a process known as adaptive thermogenesis. The signaling cascades and energy-dissipating pathways that facilitate thermogenesis have been extensively described, yet little is known about the counterbalancing negative regulatory mechanisms. Here, we identify a two-pore-domain potassium channel, KCNK3, as a built-in rheostat negatively regulating thermogenesis. Kcnk3 is transcriptionally wired into the thermogenic program by PRDM16, a master regulator of thermogenesis...
September 30, 2017: Cell
https://www.readbyqxmd.com/read/28988292/role-of-cell-cycle-regulators-in-adipose-tissue-and-whole-body-energy-homeostasis
#18
REVIEW
I C Lopez-Mejia, J Castillo-Armengol, S Lagarrigue, L Fajas
In the course of the last decades, metabolism research has demonstrated that adipose tissue is not an inactive tissue. Rather, adipocytes are key actors of whole body energy homeostasis. Numerous novel regulators of adipose tissue differentiation and function have been identified. With the constant increase of obesity and associated disorders, the interest in adipose tissue function alterations in the XXIst century has become of paramount importance. Recent data suggest that adipocyte differentiation, adipose tissue browning and mitochondrial function, lipogenesis and lipolysis are strongly modulated by the cell division machinery...
October 7, 2017: Cellular and Molecular Life Sciences: CMLS
https://www.readbyqxmd.com/read/28986166/sildenafil-induces-browning-of-subcutaneous-white-adipose-tissue-in-overweight-adults
#19
Shuguang Li, Yixiang Li, Lin Xiang, Jing Dong, Min Liu, Guangda Xiang
OBJECTIVE: To investigate that short-term treatment of sildenafil can induce browning of subcutaneous white adipose tissue (sWAT) in human adults. DESIGN: A randomized, double-blinded, placebo-controlled, parallel group trial. METHODS: Sixteen eligibility overweight male subjects were recruited, comparing 100 mg/day sildenafil versus an identical placebo therapy for 7 days. sWAT samples were collected from subjects before and after 7-day sildenafil or placebo intervention...
October 3, 2017: Metabolism: Clinical and Experimental
https://www.readbyqxmd.com/read/28983409/systems-biology-reveals-uncoupling-beyond-ucp1-in-human-white-fat-derived-beige-adipocytes
#20
Elin Nyman, Stefano Bartesaghi, Rebecka Melin Rydfalk, Sandra Eng, Charlotte Pollard, Peter Gennemark, Xiao-Rong Peng, Gunnar Cedersund
Pharmaceutical induction of metabolically active beige adipocytes in the normally energy storing white adipose tissue has potential to reduce obesity. Mitochondrial uncoupling in beige adipocytes, as in brown adipocytes, has been reported to occur via the uncoupling protein 1 (UCP1). However, several previous in vitro characterizations of human beige adipocytes have only measured UCP1 mRNA fold increase, and assumed a direct correlation with metabolic activity. Here, we provide an example of pharmaceutical induction of beige adipocytes, where increased mRNA levels of UCP1 are not translated into increased protein levels, and perform a thorough analysis of this example...
2017: NPJ Systems Biology and Applications
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