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Almudena Gómez-Hernández, Nuria Beneit, Sabela Díaz-Castroverde, Óscar Escribano
This review focuses on the contribution of white, brown, and perivascular adipose tissues to the pathophysiology of obesity and its associated metabolic and vascular complications. Weight gain in obesity generates excess of fat, usually visceral fat, and activates the inflammatory response in the adipocytes and then in other tissues such as liver. Therefore, low systemic inflammation responsible for insulin resistance contributes to atherosclerotic process. Furthermore, an inverse relationship between body mass index and brown adipose tissue activity has been described...
2016: International Journal of Endocrinology
Delphine Duteil, Milica Tosic, Franziska Lausecker, Hatice Z Nenseth, Judith M Müller, Sylvia Urban, Dominica Willmann, Kerstin Petroll, Nadia Messaddeq, Laura Arrigoni, Thomas Manke, Jan-Wilhelm Kornfeld, Jens C Brüning, Vyacheslav Zagoriy, Michael Meret, Jörn Dengjel, Toufike Kanouni, Roland Schüle
Previous work indicated that lysine-specific demethylase 1 (Lsd1) can positively regulate the oxidative and thermogenic capacities of white and beige adipocytes. Here we investigate the role of Lsd1 in brown adipose tissue (BAT) and find that BAT-selective Lsd1 ablation induces a shift from oxidative to glycolytic metabolism. This shift is associated with downregulation of BAT-specific and upregulation of white adipose tissue (WAT)-selective gene expression. This results in the accumulation of di- and triacylglycerides and culminates in a profound whitening of BAT in aged Lsd1-deficient mice...
October 18, 2016: Cell Reports
Michel J Massaad, Jia Zhou, Daisuke Tsuchimoto, Janet Chou, Haifa Jabara, Erin Janssen, Salomé Glauzy, Brennan G Olson, Henner Morbach, Toshiro K Ohsumi, Klaus Schmitz, Markianos Kyriacos, Jennifer Kane, Kumiko Torisu, Yusaku Nakabeppu, Luigi D Notarangelo, Eliane Chouery, Andre Megarbane, Peter B Kang, Eman Al-Idrissi, Hasan Aldhekri, Eric Meffre, Masayuki Mizui, George C Tsokos, John P Manis, Waleed Al-Herz, Susan S Wallace, Raif S Geha
Alterations in the apoptosis of immune cells have been associated with autoimmunity. Here, we have identified a homozygous missense mutation in the gene encoding the base excision repair enzyme Nei endonuclease VIII-like 3 (NEIL3) that abolished enzymatic activity in 3 siblings from a consanguineous family. The NEIL3 mutation was associated with fatal recurrent infections, severe autoimmunity, hypogammaglobulinemia, and impaired B cell function in these individuals. The same homozygous NEIL3 mutation was also identified in an asymptomatic individual who exhibited elevated levels of serum autoantibodies and defective peripheral B cell tolerance, but normal B cell function...
October 17, 2016: Journal of Clinical Investigation
Eun Hee Koh, Yong Chen, David A Bader, Mark P Hamilton, Bin He, Brian York, Shingo Kajimura, Sean E McGuire, Sean M Hartig
The acquisition of beige adipocyte features by white fat cells corresponds to protection against obesity-induced metabolic diseases in humans and animal models of type 2 diabetes. In adipose tissue, expression of the E2-SUMO ligase Ubiquitin Carrier Protein 9 (Ubc9) is positively correlated with markers of insulin resistance and corresponds with impaired browning of human white adipocytes. However, the molecular regulation of Ubc9 expression in adipocytes and other cells remains unclear. In this study, we demonstrated the mRNA and protein expression of Ubc9 are regulated by the microRNA miRNA-30a (miR-30a) in human subcutaneous adipocytes...
October 10, 2016: Journal of Biological Chemistry
Zhongyan Hua, Xiao Gu, Yudi Dong, Fei Tan, Zhihui Liu, Carol J Thiele, Zhijie Li
Brain-derived neurotrophic factor (BDNF) and its tyrosine kinase receptor TrkB have been reported to be associated with poor prognosis in neuroblastoma (NB) patients. Our previous studies indicated that BDNF activation of TrkB induces chemo-resistance through activation of phosphoinositide-3-kinase (PI3K)/Akt pathway. In this study, we investigated the role of BDNF/TrkB on metastasis in NB. A tetracycline-regulated TrkB-expressing NB cell line (TB3) was used. Scratch wound healing assay, Boyden chamber migration, and invasion assays were performed to study the migration and invasion of TB3 cells...
October 17, 2016: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
I Louveau, M-H Perruchot, M Bonnet, F Gondret
Both white and brown adipose tissues are recognized to be differently involved in energy metabolism and are also able to secrete a variety of factors called adipokines that are involved in a wide range of physiological and metabolic functions. Brown adipose tissue is predominant around birth, except in pigs. Irrespective of species, white adipose tissue has a large capacity to expand postnatally and is able to adapt to a variety of factors. The aim of this review is to update the cellular and molecular mechanisms associated with pre- and postnatal adipose tissue development with a special focus on pigs and ruminants...
November 2016: Animal: An International Journal of Animal Bioscience
Chelsea Hepler, Rana K Gupta
The rising incidence of obesity and associated metabolic diseases has increased the urgency in understanding all aspects of adipose tissue biology. This includes the function of adipocytes, how adipose tissue expands in obesity, and how expanded adipose tissues in adults can impact physiology. Here, we highlight the growing appreciation for the importance of de novo adipocyte differentiation to adipose tissue expansion in adult humans and animals. We detail recent efforts to identify adipose precursor populations that contribute to the physiological postnatal recruitment of white, brown, and beige adipocytes in mice, and summarize new data that reveal the complexity of adipose tissue development in vivo...
October 12, 2016: Molecular and Cellular Endocrinology
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
A Castellanos-Gonzalez, H Sparks, S Nava, W Huang, Z Zhang, K Rivas, M Hulverson, L Barrett, K K Ojo, E Fan, W C Van Voorhis, A C White
Cryptosporidium is recognized as one of the main causes of childhood diarrhea worldwide. However, the current treatment for cryptosporidiosis is suboptimal. Calcium flux is essential for entry in apicomplexan parasites. Calcium dependent protein kinases (CDPKs) are distinct from protein kinases of mammals, and the CDPK1 of the apicomplexan Cryptosporidium lack side-chains that typically block a hydrophobic pocket in protein kinases. We exploited this to develop bumped kinase inhibitors (BKI) that selectively target CDPK1...
October 12, 2016: Journal of Infectious Diseases
Ziye Xu, Jiaqi Liu, Tizhong Shan
Adipose tissues regulate energy metabolism and reproduction. There are three types of adipocytes (brown, white and beige adipocytes) in mammals. White adipocytes store energy and are closely associated with obesity and other metabolic diseases. The beige and brown adipocytes have numerous mitochondria and high levels of UCP1 that dissipates lipid to generate heat and defend against obesity. The global epidemic of obesity and its associated metabolic diseases urge an imperative need for understating the regulation of adipogenesis...
October 12, 2016: Journal of Cellular Physiology
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...
October 4, 2016: Pflügers Archiv: European Journal of Physiology
Marcelo R De Carvalho
Stingrays from the rio Tapajós basin are reviewed based on material collected from its lower (i.e. from the mouth-lake to Itaituba), middle (from about the São Luiz rapids to the confluence of rios Juruena and Teles Pires), and upper (above the Juruena-Teles Pires confluence) segments. Two new species endemic to the mid and upper Tapajós, discovered long ago and common in the ornamental fish trade, are described. Potamotrygon albimaculata sp. nov. is part of the black stingray species group, and is diagnosed by its blackish brown dorsal disc color with numerous and generally evenly-spaced small whitish spots and faint ocelli, multiple rows of thorns broadly spread on dorsal and lateral tail, pelvic fins with broadly rounded apices, and two angular cartilages with the posterior far more slender but about as wide as the anterior angular...
September 13, 2016: Zootaxa
Qingzhang Zhu, Sarbani Ghoshal, Ana Rodrigues, Su Gao, Alice Asterian, Theodore M Kamenecka, James C Barrow, Anutosh Chakraborty
Enhancing energy expenditure (EE) is an attractive strategy to combat obesity and diabetes. Global deletion of Ip6k1 protects mice from diet-induced obesity (DIO) and insulin resistance, but the tissue-specific mechanism by which IP6K1 regulates body weight is unknown. Here, we have demonstrated that IP6K1 regulates fat accumulation by modulating AMPK-mediated adipocyte energy metabolism. Cold exposure led to downregulation of Ip6k1 in murine inguinal and retroperitoneal white adipose tissue (IWAT and RWAT) depots...
October 4, 2016: Journal of Clinical Investigation
Marta Giralt, Montserrat Cairó, Francesc Villarroya
Recent research has revealed that the activity of adipose tissue (BAT) in adult humans is higher than previously thought, and that obese patients show abnormally low levels of brown fat activity. Studies in experimental animals have shown that BAT is a site of energy expenditure, and that BAT activity protects against obesity and associated metabolic diseases. The action of the sympathetic nervous activity on BAT depots is considered the main regulator of BAT activity in rodent models and possibly also in humans...
August 2016: Best Practice & Research. Clinical Endocrinology & Metabolism
Christian Schlein, Joerg Heeren
Excess and ectopic fat accumulation in obesity is a major risk factor for developing hyperlipidemia, type 2 diabetes and cardiovascular disease. The activation of brown and/or beige adipocytes is a promising target for the treatment of metabolic disorders as the combustion of excess energy by these thermogenic adipocytes may help losing weight and improving plasma parameters including triglyceride, cholesterol and glucose levels. The regulation of heat production by thermogenic adipose tissues is based on a complex crosstalk between the autonomous nervous system, intracellular and secreted factors...
August 2016: Best Practice & Research. Clinical Endocrinology & Metabolism
Florian W Kiefer
The view of adipose tissue as solely a fat storing organ has changed significantly over the past two decades with the discoveries of numerous adipocyte-secreted factors, so called adipokines, and their endocrine functions throughout the body. The newest chapter added to this story is the finding that adipose tissue is also a thermogenic organ contributing to energy expenditure through actions of specialized, heat-producing brown or beige adipocytes. In contrast to bone fide brown adipocytes, beige cells develop within white fat depots in response to various stimuli such as prolonged cold exposure, underscoring the great thermogenic plasticity of adipose tissue...
August 2016: Best Practice & Research. Clinical Endocrinology & Metabolism
Kevin Man, Vassily I Kutyavin, Ajay Chawla
Evolution of metazoans resulted in the specialization of cellular and tissue function. This was accomplished by division of labor, which allowed tissue parenchymal cells to prioritize their core functions while ancillary functions were delegated to tissue accessory cells, such as immune, stromal, and endothelial cells. In metabolic organs, the accessory cells communicate with their clients, the tissue parenchymal cells, to optimize cellular processes, allowing organisms to adapt to changes in their environment...
September 21, 2016: Cell Metabolism
Francesc Villarroya, Marion Peyrou, Marta Giralt
Regulated transcription of the uncoupling protein-1 (UCP1) gene, and subsequent UCP1 protein synthesis, is a hallmark of the acquisition of the differentiated, thermogenically competent status of brown and beige/brite adipocytes, as well as of the responsiveness of brown and beige/brite adipocytes to adaptive regulation of thermogenic activity. The 5' non-coding region of the UCP1 gene contains regulatory elements that confer tissue specificity, differentiation dependence, and neuro-hormonal regulation to UCP1 gene transcription...
October 5, 2016: Biochimie
Matthew E Gitelis, Adelaide Kaczynski, Torin Shear, Mark Deshur, Mohammad Beig, Meredith Sefa, Jonathan Silverstein, Michael Ujiki
BACKGROUND: In 2009, NorthShore University HealthSystem adapted the World Health Organization Surgical Safety Checklist (SSC) at each of its 4 hospitals. Despite evidence that SSC reduces intraoperative mistakes and increase patient safety, compliance was found to be low with the paper form. In November 2013, NorthShore integrated the SSC into the electronic health record (EHR). The aim was to increase communication between operating room (OR) personnel and to encourage best practices during the natural workflow of surgeons, anesthesiologists, and nurses...
August 16, 2016: American Journal of Surgery
Lance A Stechschulte, Chunxi Ge, Terry D Hinds, Edwin R Sanchez, Renny T Franceschi, Beata Lecka-Czernik
Peroxisome proliferator-activated receptor gamma (PPARγ) and runt-related transcription factor 2 (RUNX2) are key regulators of mesenchymal stem cell (MSC) differentiation toward adipocytes and osteoblasts, respectively. Post-translational modifications of these factors determine their activities. Dephosphorylation of PPARγ at Serine 112 (S112) is required for its adipocytic activity, whereas phosphorylation of RUNX2 at Serine 319 (S319) promotes its osteoblastic activity. Here we show that protein phosphatase 5 (PP5) reciprocally regulates each receptor by targeting each serine...
September 29, 2016: Journal of Biological Chemistry
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