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Umesh D Wankhade, Ji-Hyeon Lee, Pradeep K Dagur, Hariom Yadav, Michael Shen, Weiping Chen, Ashok B Kulkarni, J Philip McCoy, Toren Finkel, Aaron M Cypess, Sushil G Rane
OBJECTIVE: Beige/brite adipose tissue displays morphological characteristics and beneficial metabolic traits of brown adipose tissue. Previously, we showed that TGF-β signaling regulates the browning of white adipose tissue. Here, we inquired whether TGF-β signals regulated presumptive beige progenitors in white fat and investigated the TGF-β regulated mechanisms involved in beige adipogenesis. METHODS: We deleted TGF-β receptor 1 (TβRI) in adipose tissue (TβRIAdKO mice) and, using flow-cytometry based assays, identified and isolated presumptive beige progenitors located in the stromal vascular cells of white fat...
July 27, 2018: Molecular Metabolism
Alba Serrano, Madhu Asnani, Ana M Rodríguez, Andreu Palou, Joan Ribot, M Luisa Bonet
SCOPE: Resveratrol (RSV) and nicotinamide riboside (NR) are food compounds with anti-obesity actions in adult rodents. Here we assessed the long-term effects of RSV and NR mild supplementation throughout lactation on adiposity-related parameters and the appearance of the beige phenotype in white adipose tissue (WAT) in adulthood. METHODS AND RESULTS: Newborn mice received orally RSV or NR from day 2 to 20 of life. Control littermates received the vehicle. All animals were weaned onto a chow diet on day 21...
August 10, 2018: Molecular Nutrition & Food Research
Brian S Finlin, Hasiyet Memetimin, Amy L Confides, Ildiko Kasza, Beibei Zhu, Hemendra J Vekaria, Brianna Harfmann, Kelly A Jones, Zachary R Johnson, Philip M Westgate, Caroline M Alexander, Patrick G Sullivan, Esther E Dupont-Versteegden, Philip A Kern
BACKGROUND: The induction of beige adipocytes in s.c. white adipose tissue (WAT) depots of humans is postulated to improve glucose and lipid metabolism in obesity. The ability of obese, insulin-resistant humans to induce beige adipose tissue is unknown. METHODS: We exposed lean and obese research participants to cold (30-minute ice pack application each day for 10 days of the upper thigh) or treated them with the β3 agonist mirabegron. We determined beige adipose marker expression by IHC and quantitative PCR, and we analyzed mitochondrial bioenergetics and UCP activity with an Oxytherm system...
August 9, 2018: JCI Insight
Rushita A Bagchi, Bradley S Ferguson, Matthew S Stratton, Tianjing Hu, Maria A Cavasin, Lei Sun, Ying-Hsi Lin, Dianxin Liu, Pilar Londono, Kunhua Song, Maria F Pino, Lauren M Sparks, Steven R Smith, Philipp E Scherer, Sheila Collins, Edward Seto, Timothy A McKinsey
Little is known about the biological function of histone deacetylase 11 (HDAC11), which is the lone class IV HDAC. Here, we demonstrate that deletion of HDAC11 in mice stimulates brown adipose tissue (BAT) formation and beiging of white adipose tissue (WAT). Consequently, HDAC11-deficient mice exhibit enhanced thermogenic potential and, in response to high-fat feeding, attenuated obesity, improved insulin sensitivity, and reduced hepatic steatosis. Ex vivo and cell-based assays revealed that HDAC11 catalytic activity suppresses the BAT transcriptional program, in both the basal state and in response to β-adrenergic receptor signaling, through a mechanism that is dependent on physical association with BRD2, a bromodomain and extraterminal (BET) acetyl-histone-binding protein...
August 9, 2018: JCI Insight
Bronson A Haynes, Ryan W Huyck, Ashley J James, Meghan E Carter, Omnia U Gaafar, Marjorie Day, Avennette Pinto, Anca D Dobrian
Obesity is accompanied by an extensive remodeling of adipose tissue primarily via adipocyte hypertrophy. Extreme adipocyte growth results in a poor response to insulin, local hypoxia, and inflammation. By stimulating the differentiation of functional white adipocytes from progenitors, radical hypertrophy of the adipocyte population can be prevented and, consequently, the metabolic health of adipose tissue can be improved along with a reduction of inflammation. Also, by stimulating a differentiation of beige/brown adipocytes, the total body energy expenditure can be increased, resulting in weight loss...
July 17, 2018: Journal of Visualized Experiments: JoVE
Michael E Symonds, Peter Aldiss, Mark Pope, Helen Budge
Brown adipose tissue (BAT) possesses a unique uncoupling protein (UCP1) which, when activated, enables the rapid generation of heat and the oxidation of lipids or glucose or both. It is present in small amounts (~15-350 mL) in adult humans. UCP1 is rapidly activated at birth and is essential in preventing hypothermia in newborns, who rapidly generate large amounts of heat through non-shivering thermogenesis. Since the "re-discovery" of BAT in adult humans about 10 years ago, there has been an exceptional amount of research interest...
2018: F1000Research
Ann Hammarstedt, Silvia Gogg, Shahram Hedjazifar, Annika Nerstedt, Ulf Smith
The subcutaneous adipose tissue (SAT) is the largest and best storage site for excess lipids. However, it has a limited ability to expand by recruiting and/or differentiating available precursor cells. When inadequate, this leads to a hypertrophic expansion of the cells with increased inflammation, insulin resistance, and a dysfunctional prolipolytic tissue. Epi-/genetic factors regulate SAT adipogenesis and genetic predisposition for type 2 diabetes is associated with markers of an impaired SAT adipogenesis and development of hypertrophic obesity also in nonobese individuals...
October 1, 2018: Physiological Reviews
Omri Wolk, Milica Markovic, Daniel Porat, Noa Fine-Shamir, Moran Zur, Avital Beig, Arik Dahan
The goal of this work was to develop in-silico model that allows predicting segmental-dependent permeability throughout the small-intestine (SI). In-vivo permeability of 11 model drugs in three SI segments (jejunum, mid-SI, ileum) was studied in rats, creating a dataset that reflects the conditions throughout the SI. Then, a predictive model was developed, combining physicochemical drug properties influencing the underlying mechanism of passive permeability: Log P, PSA, MW , H-bond count and Log fu , with micro-environmental SI conditions...
July 25, 2018: Journal of Pharmaceutical Sciences
Wenyan Fu, Yang Liu, Christina Sun, Hang Yin
Aging of white adipose tissue (WAT) is associated with reduced insulin sensitivity, which contributes to whole-body glucose intolerance. WAT aging in mice impairs cold-induced beige adipocyte recruitment (beiging), which has been attributed to the senescence of adipose progenitor cells. Tumor suppressor p53 has also been implicated in WAT aging. However, whether p53-related cellular aging in mature white adipocytes is causative of age-impaired WAT beiging remains unknown. It is also unclear whether transient p53 inhibition can rescue WAT beiging...
July 27, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
Adriana Grigoraş, Cornelia Amalinei, Raluca Anca Balan, Simona Eliza Giuşcă, Elena Roxana Avădănei, Ludmila Lozneanu, Irina-Draga Căruntu
Firstly identified by anatomists, the fat tissue is nowadays an area of intense research due to increased global prevalence of obesity and its associated diseases. Histologically, there are four types of fat tissue cells which are currently recognized (white, brown, beige, and perivascular adipocytes). Therefore, in this study we are reviewing the most recent data regarding the origin, structure, and molecular mechanisms involved in the development of adipocytes. White adipocytes can store triglycerides as a consequence of lipogenesis, under the regulation of growth hormone or leptin and adiponectin, and release fatty acids resulted from lipolysis, under the regulation of the sympathetic nervous system, glucocorticoids, TNF-α, insulin, and natriuretic peptides...
September 2018: Annals of Anatomy, Anatomischer Anzeiger: Official Organ of the Anatomische Gesellschaft
Lu Liu, Nitin Puri, Marco Raffaele, Joseph Schragenheim, Shailendra P Singh, J Alyce Bradbury, Lars Bellner, Luca Vanella, Darryl C Zeldin, Jian Cao, Nader G Abraham
We have shown that epoxyeicosatrienoic acids (EETs), specifically 11,12- and 14,15-EETs, reduce adipogenesis in human mesenchymal stem cells and mouse preadipocytes (3T-3L1). In this study, we explore the effects of soluble epoxide hydrolase (sEH) deletion on various aspects of adipocyte-function, including programing for white vs. beige-like fat, and mitochondrial and thermogenic gene-expressions. We further hypothesize that EETs and heme-oxygenase 1 (HO-1) form a synergistic, functional module whose effects on adipocyte and vascular function is greater than the effects of sEH deletion alone...
July 21, 2018: Prostaglandins & Other Lipid Mediators
Christian Wolfrum, Leon Gabriel Straub
The adult human adipose tissue is predominantly composed of white adipocytes. However, within certain depots, adipose tissue contains thermogenically active brown-like adipocytes, which have been evolutionarily conserved in mammals. This chapter will give a brief overview on the methods used to genetically target and trace both white and brown adipocytes using techniques such as bacterial artificial chromosome (BAC) cloning to create transgenic mouse models and the tools with which genetic recombination is mediated in vivo (e...
July 20, 2018: Handbook of Experimental Pharmacology
Evanna L Mills, Kerry A Pierce, Mark P Jedrychowski, Ryan Garrity, Sally Winther, Sara Vidoni, Takeshi Yoneshiro, Jessica B Spinelli, Gina Z Lu, Lawrence Kazak, Alexander S Banks, Marcia C Haigis, Shingo Kajimura, Michael P Murphy, Steven P Gygi, Clary B Clish, Edward T Chouchani
Thermogenesis by brown and beige adipose tissue, which requires activation by external stimuli, can counter metabolic disease1 . Thermogenic respiration is initiated by adipocyte lipolysis through cyclic AMP-protein kinase A signalling; this pathway has been subject to longstanding clinical investigation2-4 . Here we apply a comparative metabolomics approach and identify an independent metabolic pathway that controls acute activation of adipose tissue thermogenesis in vivo. We show that substantial and selective accumulation of the tricarboxylic acid cycle intermediate succinate is a metabolic signature of adipose tissue thermogenesis upon activation by exposure to cold...
August 2018: Nature
Matthew D Lynes, Farnaz Shamsi, Elahu Gosney Sustarsic, Luiz O Leiria, Chih-Hao Wang, Sheng-Chiang Su, Tian Lian Huang, Fei Gao, Niven R Narain, Emily Y Chen, Aaron M Cypess, Tim J Schulz, Zachary Gerhart-Hines, Michael A Kiebish, Yu-Hua Tseng
Thermogenic fat expends energy during cold for temperature homeostasis, and its activity regulates nutrient metabolism and insulin sensitivity. We measured cold-activated lipid landscapes in circulation and in adipose tissue by MS/MSALL shotgun lipidomics. We created an interactive online viewer to visualize the changes of specific lipid species in response to cold. In adipose tissue, among the approximately 1,600 lipid species profiled, we identified the biosynthetic pathway of the mitochondrial phospholipid cardiolipin as coordinately activated in brown and beige fat by cold in wild-type and transgenic mice with enhanced browning of white fat...
July 17, 2018: Cell Reports
Michael S Kuefner, Xiong Deng, Erin J Stephenson, Kevin Pham, Edwards A Park
Secretory phospholipase A2 group IIA (PLA2G2A) is a phospholipase which has a role in inflammation, atherogenesis, and host defense. Previously, we found that PLA2G2A protects mice on high-fat diets from weight gain and insulin resistance. Here, we examined the regulation of PLA2G2A and the metabolic changes that occur in response to variations in thyroid status. In particular, the impact of PLA2G2A on the brown adipose tissue (BAT) thermogenic gene expression was explored. We induced hypothyroidism in C57BL/6 and PLA2G2A-overexpressing (IIA+) mice over a 10 wk period or treated them with thyroid hormone (T3 ) for 5 wk...
July 18, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
Adriana R Rodrigues, Maria J Salazar, Sílvia Rocha-Rodrigues, Inês O Gonçalves, Célia Cruz, Delminda Neves, Henrique Almeida, José Magalhães, Alexandra M Gouveia
BACKGROUND/OBJECTIVES: The browning of white adipose tissue (WAT) has been in the spotlight during the last years, becoming an attractive approach to combat obesity. Melanocortin neuropeptides, such as α-melanocyte-stimulating hormone (α-MSH), are well-known regulators of appetite at the central nervous system, but its role in adipocyte metabolism is poorly elucidated. This study sought to verify if α-MSH can induce transdifferentiation of white to brown/beige adipocytes and to determine whether it can ameliorate the obesity phenotype...
July 17, 2018: International Journal of Obesity: Journal of the International Association for the Study of Obesity
Ozren Stojanović, Silas Kieser, Mirko Trajkovski
Adipose tissues play an essential role in regulating the metabolic homeostasis and can be found in almost all parts of the body. Excessive adiposity leads to obesity and can contribute to metabolic and other disorders. Adipocytes show remarkable plasticity in their function, which can be pushed toward energy storage, or energy expenditure-a `browning' of fat. Browning is controlled by the cellular milieu of the adipose tissue, with sympathetic innervation and by immune responses as key integrators of the signals that promote browning...
July 11, 2018: Current Opinion in Cell Biology
Adilson Guilherme, David J Pedersen, Felipe Henriques, Alexander H Bedard, Elizabeth Henchey, Mark Kelly, Donald A Morgan, Kamal Rahmouni, Michael P Czech
OBJECTIVE: Crosstalk between adipocytes and local neurons may be an important regulatory mechanism to control energy homeostasis. We previously reported that perturbation of adipocyte de novo lipogenesis (DNL) by deletion of fatty acid synthase (FASN) expands sympathetic neurons within white adipose tissue (WAT) and stimulates the appearance of "beige" adipocytes. Here we tested whether WAT DNL activity can also influence neuronal regulation and thermogenesis in brown adipose tissue (BAT)...
June 27, 2018: Molecular Metabolism
Vijay S Limaye, Kim Knowlton, Sayantan Sarkar, Partha Sarthi Ganguly, Shyam Pingle, Priya Dutta, Sathish L M, Abhiyant Tiwari, Bhavin Solanki, Chirag Shah, Gopal Raval, Khyati Kakkad, Gufran Beig, Neha Parkhi, Anjali Jaiswal, Dileep Mavalankar
Indian cities struggle with some of the highest ambient air pollution levels in the world. While national efforts are building momentum towards concerted action to reduce air pollution, individual cities are taking action on this challenge to protect communities from the many health problems caused by this harmful environmental exposure. In 2017, the city of Ahmedabad launched a regional air pollution monitoring and risk communication project, the Air Information and Response (AIR) Plan. The centerpiece of the plan is an air quality index developed by the Indian Institute of Tropical Meteorology’s System for Air Quality and Weather Forecasting and Research program that summarizes information from 10 new continuous air pollution monitoring stations in the region, each reporting data that can help people avoid harmful exposures and inform policy strategies to achieve cleaner air...
July 10, 2018: International Journal of Environmental Research and Public Health
Amoah Yeboah-Korang, Mohammad I Beig, Mohammad Q Khan, Jay L Goldstein, Don M Macapinlac, Darryck Maurer, Amnon Sonnenberg, Claus J Fimmel
Background and Objectives: Hepatitis C virus (HCV) testing rates among U.S. birth-cohort patients have been studied extensively, limited data exists to differentiate birth-cohort screening from risk- or liver disease-based testing. This study aims to identify factors associated with HCV antibody (HCV-Ab) testing in a group of insured birth cohort patients, to determine true birth cohort testing rates, and to determine whether an electronic medical record (EMR)-driven Best Practice Alert (BPA) would improve birth cohort testing rates...
June 2018: Journal of Translational Internal Medicine
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