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https://www.readbyqxmd.com/read/28431377/metabolic-regulation-and-the-anti-obesity-perspectives-of-human-brown-fat
#1
REVIEW
Camilla Scheele, Søren Nielsen
Activation of brown adipose tissue (BAT) in adult humans increase glucose and fatty acid clearance as well as resting metabolic rate, whereas a prolonged elevation of BAT activity improves insulin sensitivity. However, substantial reductions in body weight following BAT activation has not yet been shown in humans. This observation raise the possibility for feedback mechanisms in adult humans in terms of a brown fat-brain crosstalk, possibly mediated by batokines, factors produced by and secreted from brown fat...
April 11, 2017: Redox Biology
https://www.readbyqxmd.com/read/28427098/opa1-in-lipid-metabolism-function-of-opa1-in-lipolysis-and-thermogenesis-of-adipocytes
#2
Dinh-Toi Chu, Yang Tao, Kjetil Taskén
OPA1 (Optic Atrophy 1) is a mitochondrial GTPase known to regulate fission of mitochondria. It was recently also shown to locate on lipid droplets in adipocytes where it functions as an A-kinase anchoring protein (AKAP) that mediates adrenergic control of lipolysis by facilitating PKA phosphorylation of perilipin (Plin1). In brown adipocytes indirect evidence support the notion that OPA1 regulation of fission serves to increase thermogenesis, which thereby contributes to dissipation of energy. In white adipocytes, OPA1 located on lipid droplets serves as a gatekeeper to control lipolysis induced by adrenergic agonists...
April 2017: Hormone and Metabolic Research, Hormon- und Stoffwechselforschung, Hormones et Métabolisme
https://www.readbyqxmd.com/read/28244038/flow-cytometric-isolation-and-differentiation-of-adipogenic-progenitor-cells-into-brown-and-brite-beige-adipocytes
#3
Jochen Steinbring, Antonia Graja, Anne-Marie Jank, Tim J Schulz
Aside from mature adipocytes, adipose tissue harbors several distinct cell populations including immune cells, endothelial cells, and adipogenic progenitor cells (AdPCs). AdPCs represent the reservoir of regenerative cells that replenishes adipocytes during normal cellular turnover and during times of increased demand for triglyceride-storage capacity. The worldwide increase in pathologies associated with the metabolic syndrome, such as obesity and type-2 diabetes, has heightened public and scientific interest in adipose tissues and the cell biological processes of adipose tissue formation and function...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28223294/the-%C3%AE-3-adrenergic-receptor-is-dispensable-for-browning-of-adipose-tissues
#4
Jasper M A de Jong, René T F Wouters, Nathalie Boulet, Barbara Cannon, Jan Nedergaard, Natasa Petrovic
Brown and brite/beige adipocytes are attractive therapeutic targets to treat metabolic diseases. To maximally utilize their functional potential, further understanding is required about their identities and their functional differences. Recent studies with β3-adrenergic receptor knockout mice reported that brite/beige adipocytes, but not classical brown adipocytes, require the β3-adrenergic receptor for cold-induced transcriptional activation of thermogenic genes. We aimed to further characterize this requirement of the β3-adrenergic receptor as a functional distinction between classical brown and brite/beige adipocytes...
February 21, 2017: American Journal of Physiology. Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28220393/common-and-distinct-regulation-of-human-and-mouse-brown-and-beige-adipose-tissues-a-promising-therapeutic-target-for-obesity
#5
REVIEW
Xuejiao Liu, Christopher Cervantes, Feng Liu
Obesity, which underlies various metabolic and cardiovascular diseases, is a growing public health challenge for which established therapies are inadequate. Given the current obesity epidemic, there is a pressing need for more novel therapeutic strategies that will help adult individuals to manage their weight. One promising therapeutic intervention for reducing obesity is to enhance energy expenditure. Investigations into human brown fat and the recently discovered beige/brite fat have galvanized intense research efforts during the past decade because of their pivotal roles in energy dissipation...
February 20, 2017: Protein & Cell
https://www.readbyqxmd.com/read/28123139/remodeling-of-rat-stromal-vascular-cells-to-brite-beige-adipocytes-by-prolyl-hydroxyproline
#6
Jun A Minaguchi, Sakino Ogata, Naoki Takahashi, Takuya Hirose, Hiromi Ueda, Kazushige Takehana
The aim of this study was to determine the effects of prolyl-hydroxyproline (Pro-Hyp) on the proliferation and differentiation of rat stromal-vascular cells (SVCs) being cultured in a medium with (Pro-Hyp group) or without Pro-Hyp (control group). The results showed that there was no significant difference in proliferation rate of SVCs, lipid droplet (LD) diameter or intracellular concentration of triglycerides between two groups. However, the diameter range of LDs in the Pro-Hyp group tended to be smaller than that in the control group...
March 23, 2017: Journal of Veterinary Medical Science
https://www.readbyqxmd.com/read/28099124/browning-of-white-adipose-tissue-lessons-from-experimental-models
#7
Thereza Cristina Lonzetti Bargut, Vanessa Souza-Mello, Marcia Barbosa Aguila, Carlos Alberto Mandarim-de-Lacerda
Beige or brite (brown-in-white) adipocytes are present in white adipose tissue (WAT) and have a white fat-like phenotype that when stimulated acquires a brown fat-like phenotype, leading to increased thermogenesis. This phenomenon is known as browning and is more likely to occur in subcutaneous fat depots. Browning involves the expression of many transcription factors, such as PR domain containing 16 (PRDM16) and peroxisome proliferator-activated receptor (PPAR)-γ, and of uncoupling protein (UCP)-1, which is the hallmark of thermogenesis...
January 18, 2017: Hormone Molecular Biology and Clinical Investigation
https://www.readbyqxmd.com/read/28045125/metabolic-heterogeneity-of-activated-beige-brite-adipocytes-in-inguinal-adipose-tissue
#8
Yun-Hee Lee, Sang-Nam Kim, Hyun-Jung Kwon, James G Granneman
Sustained β3 adrenergic receptor (ADRB3) activation simultaneously upregulates fatty acid synthesis and oxidation in mouse brown, beige, and white adipose tissues; however, the cellular basis of this dual regulation is not known. Treatment of mice with the ADRB3 agonist CL316,243 (CL) increased expression of fatty acid synthase (FASN) and medium chain acyl-CoA dehydrogenase (MCAD) protein within the same cells in classic brown and white adipose tissues. Surprisingly, in inguinal adipose tissue, CL-upregulated FASN and MCAD in distinct cell populations: high MCAD expression occurred in multilocular adipocytes that co-expressed UCP1+, whereas high FASN expression occurred in paucilocular adipocytes lacking detectable UCP1...
January 3, 2017: Scientific Reports
https://www.readbyqxmd.com/read/27992452/enhancement-of-adipocyte-browning-by-angiotensin-ii-type-1-receptor-blockade
#9
Kana Tsukuda, Masaki Mogi, Jun Iwanami, Harumi Kanno, Hirotomo Nakaoka, Xiao-Li Wang, Hui-Yu Bai, Bao-Shuai Shan, Masayoshi Kukida, Akinori Higaki, Toshifumi Yamauchi, Li-Juan Min, Masatsugu Horiuchi
Browning of white adipose tissue (WAT) has been highlighted as a new possible therapeutic target for obesity, diabetes and lipid metabolic disorders, because WAT browning could increase energy expenditure and reduce adiposity. The new clusters of adipocytes that emerge with WAT browning have been named 'beige' or 'brite' adipocytes. Recent reports have indicated that the renin-angiotensin system (RAS) plays a role in various aspects of adipose tissue physiology and dysfunction. The biological effects of angiotensin II, a major component of RAS, are mediated by two receptor subtypes, angiotensin II type 1 receptor (AT1R) and type 2 receptor (AT2R)...
2016: PloS One
https://www.readbyqxmd.com/read/27986537/meaningful-respirometric-measurements-of-ucp1-mediated-thermogenesis
#10
REVIEW
Yongguo Li, Tobias Fromme, Martin Klingenspor
Regarding the enormous interest in brown and brite/beige adipose tissue in the context of metabolic disease, reliable quantification of thermogenesis in these adipocytes is a central issue. This requires an assay specific for uncoupling protein 1 (UCP1) mediated thermogenesis in adherent intact cells. In a recent study we identified a major pitfall associated with established procedures generally applied for this purpose. Meaningful respirometry of UCP1-mediated thermogenesis imperatively requires activation of UCP1 and control over free fatty acid levels...
March 2017: Biochimie
https://www.readbyqxmd.com/read/27974179/browning-of-white-adipose-tissue-with-roscovitine-induces-a-distinct-population-of-ucp1-adipocytes
#11
Hong Wang, Libin Liu, Jean Z Lin, Tamar R Aprahamian, Stephen R Farmer
Brown-like adipocytes exist in several adipose depots including white (WAT) as well as brown (BAT). Activation of these UCP1(+) cells is a potential therapeutic strategy to combat obesity. Studies have shown that posttranslational modifications of PPARγ regulate select adipocyte programs. Deacetylation of K268 and K293 in the ligand-binding domain of PPARγ by Sirt1 induces browning of WAT. Phosphorylation of S273 of PPARγ by CDK5 or ERK stimulates a diabetogenic program of gene expression in WAT. Here, we report that roscovitine, a CDK inhibitor, prevents S273 phosphorylation and promotes formation of UCP1(+) (brite) adipocytes in WAT...
December 13, 2016: Cell Metabolism
https://www.readbyqxmd.com/read/27923808/ucp1-inhibition-in-cidea-overexpressing-mice-is-physiologically-counteracted-by-brown-adipose-tissue-hyperrecruitment
#12
Alexander W Fischer, Irina G Shabalina, Charlotte L Mattsson, Gustavo Abreu-Vieira, Barbara Cannon, Jan Nedergard, Natasa Petrovic
Cidea is a gene highly expressed in thermogenesis-competent (UCP1-containing) adipose cells, both brown and brite/beige. Here we initially demonstrate a remarkable adipose-depot specific regulation of Cidea expression. In classical brown fat, Cidea mRNA is expressed continuously and invariably, irrespective of tissue recruitment. However, Cidea protein levels are regulated posttranscriptionally, being conspicuously induced in the thermogenically recruited state. In contrast, in brite fat, Cidea protein levels are regulated at the transcriptional level, and Cidea mRNA and protein levels are proportional to tissue "briteness"...
December 6, 2016: American Journal of Physiology. Endocrinology and Metabolism
https://www.readbyqxmd.com/read/27923458/micrornas-in-adipocyte-formation-and-obesity
#13
REVIEW
Marcel Scheideler
The worldwide epidemic of obesity demands novel and more effective therapeutic approaches. Fat cells are at the core of energy metabolism trying either to cope with a positive energy balance by hypertrophy and hyperplasia of energy storing white adipocytes or to counteract obesity by the induction of non-shivering thermogenesis in energy combusting brite/brown adipocytes. However, the comprehensive regulatory network of adipocyte formation remains to be elucidated. MicroRNAs are an emerging class of important regulatory determinants in many biological processes and diseases, including adipocyte formation and obesity...
October 2016: Best Practice & Research. Clinical Endocrinology & Metabolism
https://www.readbyqxmd.com/read/27798628/mycobacterium-tuberculosis-lineage-4-comprises-globally-distributed-and-geographically-restricted-sublineages
#14
David Stucki, Daniela Brites, Leïla Jeljeli, Mireia Coscolla, Qingyun Liu, Andrej Trauner, Lukas Fenner, Liliana Rutaihwa, Sonia Borrell, Tao Luo, Qian Gao, Midori Kato-Maeda, Marie Ballif, Matthias Egger, Rita Macedo, Helmi Mardassi, Milagros Moreno, Griselda Tudo Vilanova, Janet Fyfe, Maria Globan, Jackson Thomas, Frances Jamieson, Jennifer L Guthrie, Adwoa Asante-Poku, Dorothy Yeboah-Manu, Eddie Wampande, Willy Ssengooba, Moses Joloba, W Henry Boom, Indira Basu, James Bower, Margarida Saraiva, Sidra E G Vasconcellos, Philip Suffys, Anastasia Koch, Robert Wilkinson, Linda Gail-Bekker, Bijaya Malla, Serej D Ley, Hans-Peter Beck, Bouke C de Jong, Kadri Toit, Elisabeth Sanchez-Padilla, Maryline Bonnet, Ana Gil-Brusola, Matthias Frank, Veronique N Penlap Beng, Kathleen Eisenach, Issam Alani, Perpetual Wangui Ndung'u, Gunturu Revathi, Florian Gehre, Suriya Akter, Francine Ntoumi, Lynsey Stewart-Isherwood, Nyanda E Ntinginya, Andrea Rachow, Michael Hoelscher, Daniela Maria Cirillo, Girts Skenders, Sven Hoffner, Daiva Bakonyte, Petras Stakenas, Roland Diel, Valeriu Crudu, Olga Moldovan, Sahal Al-Hajoj, Larissa Otero, Francesca Barletta, E Jane Carter, Lameck Diero, Philip Supply, Iñaki Comas, Stefan Niemann, Sebastien Gagneux
Generalist and specialist species differ in the breadth of their ecological niches. Little is known about the niche width of obligate human pathogens. Here we analyzed a global collection of Mycobacterium tuberculosis lineage 4 clinical isolates, the most geographically widespread cause of human tuberculosis. We show that lineage 4 comprises globally distributed and geographically restricted sublineages, suggesting a distinction between generalists and specialists. Population genomic analyses showed that, whereas the majority of human T cell epitopes were conserved in all sublineages, the proportion of variable epitopes was higher in generalists...
December 2016: Nature Genetics
https://www.readbyqxmd.com/read/27797173/dipeptidyl-vinyl-sulfone-as-a-novel-chemical-tool-to-inhibit-hmgb1-nlrp3-inflammasome-and-inflamma-mirs-in-a%C3%AE-mediated-microglial-inflammation
#15
Ana S Falcão, Luís A R Carvalho, Gonçalo Lidónio, Ana R Vaz, Susana D Lucas, Rui Moreira, Dora Brites
Rapid microglial activation and associated inflammatory pathways contribute to immune-defense and tissue repair in the central nervous system (CNS). However, persistent activation of these cells will ultimately result in vast production of pro-inflammatory mediators and other neurotoxic factors, which may induce neuronal damage and contribute to chronic neurodegenerative diseases, as Alzheimer's disease (AD). Therefore, small molecules with immunomodulatory effects on microglia may be considered as potential tools to counteract their proinflammatory phenotype and neuroimmune dysregulation in such disorders...
January 18, 2017: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/27742571/regulation-of-brown-and-beige-fat-by-micrornas
#16
REVIEW
Yong Chen, Ruping Pan, Alexander Pfeifer
MicroRNAs (miRNAs) are small non-coding RNA molecules consisting of approximately 20 to 22 nucleotides. They play a very important role in the regulation of gene expression. miRNAs can be found in different species and a variety of organs and tissues including adipose tissue. There are two types of adipose tissue in mammals: White adipose tissue (WAT) is the largest energy storage, whereas brown adipose tissue (BAT) dissipates energy to maintain body temperature. BAT was first identified in hibernating animals and newborns as a defense against cold...
October 11, 2016: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/27704210/fat-tissues-the-brite-and-the-dark-sides
#17
REVIEW
Yong Chen, Ruping Pan, Alexander Pfeifer
Fat tissue is well known for its capacity to store energy and its detrimental role in obesity and metaflammation. However, humans possess different types of fat that have different functions in physiology and metabolic diseases. Apart from white adipose tissue (WAT), the body's main energy storage, there is also brown adipose tissue (BAT) that dissipates energy as a defense against cold and maintains energy balance for the whole body. BAT is present not only in newborns but also in adult humans and its mass correlates with leanness...
November 2016: Pflügers Archiv: European Journal of Physiology
https://www.readbyqxmd.com/read/27695946/browning-of-subcutaneous-fat-and-higher-surface-temperature-in-response-to-phenotype-selection-for-advanced-endurance-exercise-performance-in-male-duhtp-mice
#18
J Brenmoehl, D Ohde, E Albrecht, C Walz, A Tuchscherer, A Hoeflich
For the assessment of genetic or conditional factors of fat cell browning, novel and polygenic animal models are required. Therefore, the long-term selected polygenic mouse line DUhTP originally established in Dummerstorf for high treadmill performance is used. DUhTP mice are characterized by increased fat accumulation in the sedentary condition and elevated fat mobilization during mild voluntary physical activity. In the present study, the phenotype of fat cell browning of subcutaneous fat and a potential effect on oral glucose tolerance, an indicator of metabolic health, were addressed in DUhTP mice...
February 2017: Journal of Comparative Physiology. B, Biochemical, Systemic, and Environmental Physiology
https://www.readbyqxmd.com/read/27665765/targeting-gliomas-can-a-new-alkylating-hybrid-compound-make-a-difference
#19
Rui Pinheiro, Cláudia Braga, Gisela Santos, Maria R Bronze, Maria J Perry, Rui Moreira, Dora Brites, Ana S Falcão
Glioblastoma (GBM) is the most common and aggressive type of brain tumor in adults. The triazene Temozolomide (TMZ), an alkylating drug, is the classical chemotherapeutic agent for gliomas, but has been disappointing against the highly invasive and resistant nature of GBM. Hybrid compounds may open new horizons within this challenge. The multicomponent therapeutic strategy here used resides on a combination of two repurposing drugs acting by different but potentially synergistic mechanisms, improved efficacy, and lower resistance effects...
January 18, 2017: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/27639810/potential-for-brain-accessibility-and-analysis-of-stability-of-selected-flavonoids-in-relation-to-neuroprotection-in-vitro
#20
Lea Pogačnik, Katja Pirc, Inês Palmela, Mihaela Skrt, Kwang S Kim, Dora Brites, Maria Alexandra Brito, Nataša Poklar Ulrih, Rui F M Silva
Natural food sources constitute a promising source of new compounds with neuroprotective properties, once they have the ability to reach the brain. Our aim was to evaluate the brain accessibility of quercetin, epigallocatechin gallate (EGCG) and cyanidin-3-glucoside (C3G) in relation to their neuroprotective capability. Primary cortical neuron cultures were exposed to oxidative insult in the absence and presence of the selected compounds, and neuroprotection was assessed through evaluation of apoptotic-like and necrotic-like cell death...
November 15, 2016: Brain Research
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