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https://www.readbyqxmd.com/read/28539390/mfn2-deletion-in-brown-adipose-tissue-protects-from-insulin-resistance-and-impairs-thermogenesis
#1
Kiana Mahdaviani, Ilan Y Benador, Shi Su, Raffi A Gharakhanian, Linsey Stiles, Kyle M Trudeau, Maria Cardamone, Violeta Enríquez-Zarralanga, Eleni Ritou, Tamar Aprahamian, Marcus F Oliveira, Barbara E Corkey, Valentina Perissi, Marc Liesa, Orian S Shirihai
BAT-controlled thermogenic activity is thought to be required for its capacity to prevent the development of insulin resistance. This hypothesis predicts that mediators of thermogenesis may help prevent diet-induced insulin resistance. We report that the mitochondrial fusion protein Mitofusin 2 (Mfn2) in BAT is essential for cold-stimulated thermogenesis, but promotes insulin resistance in obese mice. Mfn2 deletion in mice through Ucp1-cre (BAT-Mfn2-KO) causes BAT lipohypertrophy and cold intolerance. Surprisingly however, deletion of Mfn2 in mice fed a high fat diet (HFD) results in improved insulin sensitivity and resistance to obesity, while impaired cold-stimulated thermogenesis is maintained...
May 24, 2017: EMBO Reports
https://www.readbyqxmd.com/read/28538730/blocking-fsh-induces-thermogenic-adipose-tissue-and-reduces-body-fat
#2
Peng Liu, Yaoting Ji, Tony Yuen, Elizabeth Rendina-Ruedy, Victoria E DeMambro, Samarth Dhawan, Wahid Abu-Amer, Sudeh Izadmehr, Bin Zhou, Andrew C Shin, Rauf Latif, Priyanthan Thangeswaran, Animesh Gupta, Jianhua Li, Valeria Shnayder, Samuel T Robinson, Yue Eric Yu, Xingjian Zhang, Feiran Yang, Ping Lu, Yu Zhou, Ling-Ling Zhu, Douglas J Oberlin, Terry F Davies, Michaela R Reagan, Aaron Brown, T Rajendra Kumar, Solomon Epstein, Jameel Iqbal, Narayan G Avadhani, Maria I New, Henrik Molina, Jan B van Klinken, Edward X Guo, Christoph Buettner, Shozeb Haider, Zhuan Bian, Li Sun, Clifford J Rosen, Mone Zaidi
Menopause is associated with bone loss and enhanced visceral adiposity. A polyclonal antibody that targets the β-subunit of the pituitary hormone follicle-stimulating hormone (Fsh) increases bone mass in mice. Here, we report that this antibody sharply reduces adipose tissue in wild-type mice, phenocopying genetic haploinsufficiency for the Fsh receptor gene Fshr. The antibody also causes profound beiging, increases cellular mitochondrial density, activates brown adipose tissue and enhances thermogenesis. These actions result from the specific binding of the antibody to the β-subunit of Fsh to block its action...
May 24, 2017: Nature
https://www.readbyqxmd.com/read/28533422/paternal-hyperglycemia-in-rats-exacerbates-the-development-of-obesity-in-offspring
#3
Xiaoqin Shi, Xinyu Li, Yi Hou, Xuemei Cao, Yuyao Zhang, Heng Wang, Hongying Wang, Chuan Peng, Jibin Li, Qifu Li, Chaodong Wu, Xiaoqiu Xiao
Parental history with obesity or diabetes will increase the risk for developing metabolic diseases in offspring. However, literatures as to transgenerational inheritance of metabolic dysfunctions through male lineage are relatively scarce. In current study, we aimed to evaluate influences of paternal hyperglycemia on metabolic phenotypes in offspring. Male SD rats were ip injected with streptozotocin (STZ) or citrate buffer (CB, as control). STZ-injected rats with glucose levels higher than 16 mM were selected to breed with normal female rats...
May 22, 2017: Journal of Endocrinology
https://www.readbyqxmd.com/read/28515438/mitochondrial-retrograde-signaling-connects-respiratory-capacity-to-thermogenic-gene-expression
#4
Minwoo Nam, Thomas E Akie, Masato Sanosaka, Siobhan M Craige, Shashi Kant, John F Keaney, Marcus P Cooper
Mitochondrial respiration plays a crucial role in determining the metabolic state of brown adipose tissue (BAT), due to its direct roles in thermogenesis, as well as through additional mechanisms. Here, we show that respiration-dependent retrograde signaling from mitochondria to nucleus contributes to genetic and metabolic reprogramming of BAT. In mouse BAT, ablation of LRPPRC (LRP130), a potent regulator of mitochondrial transcription and respiratory capacity, triggers down-regulation of thermogenic genes, promoting a storage phenotype in BAT...
May 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28507313/chronic-intrahypothalamic-rather-than-subcutaneous-liraglutide-treatment-reduces-body-weight-gain-and-stimulates-the-melanocortin-receptor-system
#5
K Kaineder, T Birngruber, G Rauter, B Obermüller, J Eichler, J Münzker, W Al-Zoughbi, S I Mautner, S S Torekov, B Hartmann, P Kotzbeck, T R Pieber
BACKGROUND: The GLP-1 receptor agonist liraglutide is marketed for obesity treatment where it induces body weight reduction possibly via the hypothalamus, which regulates energy homeostasis. In animal studies, acute liraglutide treatment triggers satiety, weight loss and activates thermogenesis in adipose tissue. However, the precise mechanisms how liraglutide affects in particular chronic weight loss are still under investigation. OBJECTIVES: We aimed to evaluate whether chronic hypothalamic or chronic subcutaneous administration of liraglutide induces sustained weight loss through altered adipose tissue function and to what extent hypothalamic neuronal appetite regulators are involved in the liraglutide-induced weight loss in healthy lean rats on a normal diet...
April 25, 2017: International Journal of Obesity: Journal of the International Association for the Study of Obesity
https://www.readbyqxmd.com/read/28507012/dietary-factors-promoting-brown-and-beige-fat-development-and-thermogenesis
#6
REVIEW
Meshail Okla, Jiyoung Kim, Karsten Koehler, Soonkyu Chung
Brown adipose tissue (BAT) is a specialized fat tissue that has a high capacity to dissociate cellular respiration from ATP utilization, resulting in the release of stored energy as heat. Adult humans possess a substantial amount of BAT in the form of constitutively active brown fat or inducible beige fat. BAT activity in humans is inversely correlated with adiposity, blood glucose concentrations, and insulin sensitivity; this suggests that strategies aimed at BAT-mediated bioenergetics are an attractive therapeutic target in combating the continuing epidemic of obesity and diabetes...
May 2017: Advances in Nutrition
https://www.readbyqxmd.com/read/28494871/mirna-32-drives-brown-fat-thermogenesis-and-trans-activates-subcutaneous-white-fat-browning-in-mice
#7
Raymond Ng, Nurul Attiqah Hussain, Qiongyi Zhang, Chengwei Chang, Hongyu Li, Yanyun Fu, Lei Cao, Weiping Han, Walter Stunkel, Feng Xu
Brown adipose tissue (BAT) activation and subcutaneous white fat browning are essential components of the thermogenic response to cold stimulus in mammals. microRNAs have been shown to regulate both processes in cis. Here, we identify miR-32 as a BAT-specific super-enhancer-associated miRNA in mice that is selectively expressed in BAT and further upregulated during cold exposure. Inhibiting miR-32 in vivo led to impaired cold tolerance, decreased BAT thermogenesis, and compromised white fat browning as a result of reduced serum FGF21 levels...
May 9, 2017: Cell Reports
https://www.readbyqxmd.com/read/28486585/cold-adaptation-in-pigs-depends-on-ucp3-in-beige-adipocytes
#8
Jun Lin, Chunwei Cao, Cong Tao, Rongcai Ye, Meng Dong, Qiantao Zheng, Chao Wang, Xiaoxiao Jiang, Guosong Qin, Changguo Yan, Kui Li, John R Speakman, Yanfang Wang, Wanzhu Jin, Jianguo Zhao
Pigs lack functional UCP1 making them susceptible to cold. Nevertheless, several pig breeds are known to be cold resistant. The molecular mechanism(s) enabling such adaptation are currently unknown. Here, we show that this resistance is not dependent on shivering, but rather depends on UCP3 and white adipose tissue (WAT) browning. In two cold-resistant breeds (Tibetan and Min), but not a cold-sensitive breed (Bama), WAT browning was induced after cold exposure. Beige adipocytes from Tibetan pigs exhibited greater oxidative capacity than those from Bama pigs...
May 9, 2017: Journal of Molecular Cell Biology
https://www.readbyqxmd.com/read/28481291/inflammation-downregulates-ucp1-expression-in-brown-adipocytes-potentially-via-sirt1-and-dbc1-interaction
#9
Mark K Nøhr, Natalia Bobba, Bjørn Richelsen, Sten Lund, Steen B Pedersen
Brown adipose tissue thermogenesis at the cost of energy is not only important for the development of obesity, but also possesses great promise in anti-obesity treatment. Uncoupling protein 1 (UCP1) expression has been reported to be under control of the intracellular deacetylase SIRT1. Here, we investigated the effect and mechanism of inflammation and sirtuin-1 (SIRT1) activation on the induction of thermogenic genes in immortalized brown adipocytes incubated with LPS or IL1β and mice with elevated inflammatory tone...
May 8, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28481288/an-additive-effect-of-promoting-thermogenic-gene-expression-in-mice-adipose-derived-stromal-vascular-cells-by-combination-of-rosiglitazone-and-cl316-243
#10
You-Lei Li, Xiao Li, Tian-Tuan Jiang, Jia-Min Fan, Xue-Li Zheng, Xin-E Shi, Tai-Yong Yu, Gui-Yan Chu, Gong-She Yang
It is well-documented that CL316,243 (a β3 agonist) or rosiglitazone (a PPARγ agonist) can induce white adipocyte populations to brown-like adipocytes, thus increasing energy consumption and combating obesity. However, whether there is a combined effect remains unknown. In the present study, stromal vascular cells of inguinal white adipose tissue (iWAT-SVCs for short) from mice were cultured and induced into browning by CL316,243, rosiglitazone, or both. Results showed that a combination of CL316,243 and rosiglitazone significantly upregulated the expression of the core thermogenic gene Ucp1 as well as genes related with mitochondrial function (Cidea, Cox5b, Cox7a1, Cox8b, and Cycs), compared with the treatment of CL316,243 or rosiglitazone alone...
May 8, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28473440/deficiency-of-lrp1-in-mature-adipocytes-promotes-diet-induced-inflammation-and-atherosclerosis-brief-report
#11
Eddy S Konaniah, David G Kuhel, Joshua E Basford, Neal L Weintraub, David Y Hui
OBJECTIVE: Mice with adipocyte-specific inactivation of low-density lipoprotein receptor-related protein-1 (LRP1) are resistant to diet-induced obesity and hyperglycemia because of compensatory thermogenic response by muscle. However, the physiological function of LRP1 in mature adipocytes and its role in cardiovascular disease modulation are unknown. This study compared perivascular adipose tissues (PVAT) from wild-type (adLrp1(+/+)) and adipocyte-specific LRP1 knockout (adLrp1(-/-)) mice in modulation of atherosclerosis progression...
June 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/28469146/optical-visualisation-of-thermogenesis-in-stimulated-single-cell-brown-adipocytes
#12
Rókus Kriszt, Satoshi Arai, Hideki Itoh, Michelle H Lee, Anna G Goralczyk, Xiu Min Ang, Aaron M Cypess, Andrew P White, Farnaz Shamsi, Ruidan Xue, Jung Yeol Lee, Sung-Chan Lee, Yanyan Hou, Tetsuya Kitaguchi, Thankiah Sudhaharan, Shin'ichi Ishiwata, E Birgitte Lane, Young-Tae Chang, Yu-Hua Tseng, Madoka Suzuki, Michael Raghunath
The identification of brown adipose deposits in adults has led to significant interest in targeting this metabolically active tissue for treatment of obesity and diabetes. Improved methods for the direct measurement of heat production as the signature function of brown adipocytes (BAs), particularly at the single cell level, would be of substantial benefit to these ongoing efforts. Here, we report the first application of a small molecule-type thermosensitive fluorescent dye, ERthermAC, to monitor thermogenesis in BAs derived from murine brown fat precursors and in human brown fat cells differentiated from human neck brown preadipocytes...
May 3, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28467890/brown-and-brite-adipocytes-same-function-but-different-origin-and-response
#13
REVIEW
Dinh-Toi Chu, Barbara Gawronska-Kozak
Inducing brown adipocytes in white adipose tissues is a promising target to combat obesity and its related disorders in human beings. This goal has been especially encouraged by new important discoveries of human brown adipose tissues. The accumulating evidence confirms the presence of active brown adipocytes, not only in newborns, but also in adult humans. In rodents, there are two populations of the Ucp1-expressing adipocytes with well characterized-thermogenic functions, classical interscapular brown adipocytes and brite/beige adipocytes (brown adipocytes that are induced in white adipose tissues)...
April 30, 2017: Biochimie
https://www.readbyqxmd.com/read/28465400/the-significance-of-beige-and-brown-fat-in-humans
#14
Florian W Kiefer
Promotion of brown adipose tissue (BAT) activity or browning of white adipose tissue has shown great potential as anti-obesity strategy in numerous preclinical models. The discovery of active BAT in humans and the recent advances in the understanding of human BAT biology and function have significantly propelled this field of research. Pharmacological stimulation of energy expenditure to counteract obesity has always been an intriguing therapeutic concept; with the identification of the specific molecular pathways of brown fat function this idea has now become as realistic as ever...
May 2, 2017: Endocrine Connections
https://www.readbyqxmd.com/read/28461471/lsd1-prevents-age-programed-loss-of-beige-adipocytes
#15
Delphine Duteil, Milica Tosic, Dominica Willmann, Anastasia Georgiadi, Toufike Kanouni, Roland Schüle
Aging is accompanied by major changes in adipose tissue distribution and function. In particular, with time, thermogenic-competent beige adipocytes progressively gain a white adipocyte morphology. However, the mechanisms controlling the age-related transition of beige adipocytes to white adipocytes remain unclear. Lysine-specific demethylase 1 (Lsd1) is an epigenetic eraser enzyme positively regulating differentiation and function of adipocytes. Here we show that Lsd1 levels decrease in aging inguinal white adipose tissue concomitantly with beige fat cell decline...
May 1, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28459435/brown-adipose-tissue-macrophages-control-tissue-innervation-and-homeostatic-energy-expenditure
#16
Yochai Wolf, Sigalit Boura-Halfon, Nina Cortese, Zhana Haimon, Hadas Sar Shalom, Yael Kuperman, Vyacheslav Kalchenko, Alexander Brandis, Eyal David, Yifat Segal-Hayoun, Louise Chappell-Maor, Avraham Yaron, Steffen Jung
Tissue macrophages provide immunological defense and contribute to the establishment and maintenance of tissue homeostasis. Here we used constitutive and inducible mutagenesis to delete the nuclear transcription regulator Mecp2 in macrophages. Mice that lacked the gene encoding Mecp2, which is associated with Rett syndrome, in macrophages did not show signs of neurodevelopmental disorder but displayed spontaneous obesity, which was linked to impaired function of brown adipose tissue (BAT). Specifically, mutagenesis of a BAT-resident Cx3Cr1(+) macrophage subpopulation compromised homeostatic thermogenesis but not acute, cold-induced thermogenesis...
June 2017: Nature Immunology
https://www.readbyqxmd.com/read/28448947/traveling-from-the-hypothalamus-to-the-adipose-tissue-the-thermogenic-pathway
#17
REVIEW
Cristina Contreras, Rubén Nogueiras, Carlos Diéguez, Kamal Rahmouni, Miguel López
Brown adipose tissue (BAT) is a specialized tissue critical for non-shivering thermogenesis producing heat through mitochondrial uncoupling; whereas white adipose tissue (WAT) is responsible of energy storage in the form of triglycerides. Another type of fat has been described, the beige adipose tissue; this tissue emerges in existing WAT depots but with thermogenic ability, a phenomenon known as browning. Several peripheral signals relaying information about energy status act in the brain, particularly the hypothalamus, to regulate thermogenesis in BAT and browning of WAT...
April 15, 2017: Redox Biology
https://www.readbyqxmd.com/read/28446594/pioneering-ebf2-remodels-the-brown-fat-chromatin-landscape
#18
Jiexin Wang, Peter Tontonoz
In this issue of Genes & Development, Shapira and colleagues (pp. 660-673) outline mechanisms by which the brown fat transcription factor early B-cell factor 2 (EBF2) selectively activates brown lineage-specific gene expression. The investigators show that EBF2 interacts with and recruits a tissue-specific BAF chromatin remodeling complex to brown fat gene enhancers, thereby regulating chromatin accessibility. Their findings provide important insight into epigenetic regulation of adipocyte fate and thermogenic gene expression...
April 1, 2017: Genes & Development
https://www.readbyqxmd.com/read/28444942/combined-inhibition-of-autophagy-protein-5-and-galectin-1-by-thiodigalactoside-reduces-diet-induced-obesity-through-induction-of-white-fat-browning
#19
Hilal Ahmad Parray, Jong Won Yun
Our previous study demonstrated that thiodigalactoside (TDG) ameliorates obesity by targeted inhibition of galectin-1 (GAL1). Here, for the first time, we report the unexpected role of GAL1 and ATG5 inhibition by TDG in lipid metabolism. Core thermogenic marker proteins and genes were highly induced in white adipose tissue (WAT) of rats fed a high fat diet (HFD) and TDG, resulting in the significant development of brown fat-like adipocytes in inguinal WAT. TDG treatment reduced weight gain and fat mass as well as activated brown adipose tissue (BAT) in HFD-fed rats...
April 26, 2017: IUBMB Life
https://www.readbyqxmd.com/read/28443906/the-enhanced-anti-obesity-effect-and-reduced-gastric-mucosa-irritation-of-capsaicin-loaded-nanoemulsions
#20
Muwen Lu, Yong Cao, Chi-Tang Ho, Qingrong Huang
Capsaicin (CAP), the major active component of chili peppers, is known to have thermogenic and weight-loss potential. The aim of this study was to investigate the anti-obesity effects of capsaicin-loaded nanoemulsions (C-NE) on male Sprague Dawley (SD) rats treated with a high-fat diet (HFD). The food grade C-NE was prepared using capsaicin, medium chain triacylglycerols (MCT) (Neobee 1053), sucrose stearate S-370, Tween 80 and distilled water with an emulsion droplet size of 168 nm and a capsaicin loading of 80...
May 24, 2017: Food & Function
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