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https://www.readbyqxmd.com/read/28547916/non-shivering-thermogenesis-as-a-mechanism-to-facilitate-sustainable-weight-loss
#1
REVIEW
B F Palmer, D J Clegg
Currently, there is a significant percentage of the population who are or will be classified as obese, necessitating novel strategies to facilitate sustainable weight loss. Reductions in basal metabolic rate occur in the face of weight loss and pose formidable barriers to individuals attempting to sustain meaningful weight reductions. Here, we discuss the mechanisms by which non-shivering thermogenesis may provide insight into metabolic pathways that can become druggable targets to facilitate sustainable weight loss...
May 25, 2017: Obesity Reviews: An Official Journal of the International Association for the Study of Obesity
https://www.readbyqxmd.com/read/28539390/mfn2-deletion-in-brown-adipose-tissue-protects-from-insulin-resistance-and-impairs-thermogenesis
#2
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
#3
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/28532548/mtorc1-in-agrp-neurons-integrates-exteroceptive-and-interoceptive-food-related-cues-in-the-modulation-of-adaptive-energy-expenditure-in-mice
#4
Luke K Burke, Tamana Darwish, Althea R Cavanaugh, Sam Virtue, Emma Roth, Joanna Morro, Shun-Mei Liu, Jing Xia, Jeffrey W Dalley, Keith Burling, Streamson Chua, Toni Vidal-Puig, Gary J Schwartz, Clémence Blouet
Energy dissipation through interscapular brown adipose tissue (iBAT) thermogenesis is an important contributor to adaptive energy expenditure. However, it remains unresolved how acute and chronic changes in energy availability are detected by the brain to adjust iBAT activity and maintain energy homeostasis. Here, we provide evidence that AGRP inhibitory tone to iBAT represents an energy-sparing circuit that integrates environmental food cues and internal signals of energy availability. We establish a role for the nutrient-sensing mTORC1 signaling pathway within AGRP neurons in the detection of environmental food cues and internal signals of energy availability, and in the bi-directional control of iBAT thermogenesis during nutrient deficiency and excess...
May 23, 2017: ELife
https://www.readbyqxmd.com/read/28525362/fgf21-receptor-agonists-an-emerging-therapeutic-class-for-obesity-related-diseases
#5
Junichiro Sonoda, Mark Z Chen, Amos Baruch
Fibroblast growth factor 21 (FGF21) analogs and FGF21 receptor agonists (FGF21RAs) that mimic FGF21 ligand activity constitute the new "FGF21-class" of anti-obesity and anti-diabetic molecules that improve insulin sensitivity, ameliorate hepatosteatosis and promote weight loss. The metabolic actions of FGF21-class proteins in obese mice are attributed to stimulation of brown fat thermogenesis and increased secretion of adiponectin. The therapeutic utility of this class of molecules is being actively investigated in clinical trials for the treatment of type 2 diabetes and non-alcoholic steatohepatitis (NASH)...
May 19, 2017: Hormone Molecular Biology and Clinical Investigation
https://www.readbyqxmd.com/read/28520765/an-integrative-analysis-of-tissue-specific-transcriptomic-and-metabolomic-responses-to-short-term-dietary-methionine-restriction-in-mice
#6
Sujoy Ghosh, Laura A Forney, Desiree Wanders, Kirsten P Stone, Thomas W Gettys
Dietary methionine restriction (MR) produces a coordinated series of transcriptional responses in peripheral tissues that limit fat accretion, remodel lipid metabolism in liver and adipose tissue, and improve overall insulin sensitivity. Hepatic sensing of reduced methionine leads to induction and release of fibroblast growth factor 21 (FGF21), which acts centrally to increase sympathetic tone and activate thermogenesis in adipose tissue. FGF21 also has direct effects in adipose to enhance glucose uptake and oxidation...
2017: PloS One
https://www.readbyqxmd.com/read/28515438/mitochondrial-retrograde-signaling-connects-respiratory-capacity-to-thermogenic-gene-expression
#7
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/28511798/induction-of-copper-and-iron-in-acute-cold-stimulated-brown-adipose-tissues
#8
Chao Wang, Xiaojuan Liang, Cong Tao, Xiaolei Yao, Yajun Wang, Yanfang Wang, Kui Li
Copper (Cu) and iron (Fe), the enzymatic cofactors required for various biochemical processes, have been recently linked to lipid metabolism. Adipose tissues play central roles in energy balance and whether copper and iron homeostasis is involved in cold-stimulated energy metabolism remain unknown. In this study, the Cu and Fe contents in interscapular brown adipose tissue (BAT) and subcutaneous white adipose tissue (WAT) from mice at different developmental stages were measured. Our results revealed the dynamic changes of Cu and Fe levels during development, suggesting their potential roles in energy homeostasis...
May 13, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28507313/chronic-intrahypothalamic-rather-than-subcutaneous-liraglutide-treatment-reduces-body-weight-gain-and-stimulates-the-melanocortin-receptor-system
#9
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/28507087/influence-of-environmental-temperature-on-risk-of-gestational-diabetes
#10
Gillian L Booth, Jin Luo, Alison L Park, Denice S Feig, Rahim Moineddin, Joel G Ray
BACKGROUND: Cold-induced thermogenesis is known to improve insulin sensitivity, which may become increasingly relevant in the face of global warming. The aim of this study was to examine the relation between outdoor air temperature and the risk of gestational diabetes mellitus. METHODS: We identified all births in the Greater Toronto Area from 2002 to 2014 using administrative health databases. Generalized estimating equations were used to examine the relation between the mean 30-day outdoor air temperature before the time of gestational diabetes mellitus screening and the likelihood of diagnosis of gestational diabetes mellitus based on a validated algorithm using hospital records and physician service claims...
May 15, 2017: CMAJ: Canadian Medical Association Journal, Journal de L'Association Medicale Canadienne
https://www.readbyqxmd.com/read/28507012/dietary-factors-promoting-brown-and-beige-fat-development-and-thermogenesis
#11
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/28501702/brown-adipose-tissue-activation-by-rutin-ameliorates-polycystic-ovary-syndrome-in-rat
#12
Tao Hu, Xiaoxue Yuan, Rongcai Ye, Huiqiao Zhou, Jun Lin, Chuanhai Zhang, Hanlin Zhang, Gang Wei, Meng Dong, Yuanyuan Huang, Wonchung Lim, Qingsong Liu, Hyuek Jong Lee, Wanzhu Jin
Polycystic ovary syndrome (PCOS) is a complex endocrinopathy that is characterized by anovulation, hyperandrogenism and polycystic ovary. However, there is a lack of effective treatment for PCOS at present because the pathologic cause of PCOS has not been elucidated. Although it has been known that brown adipose tissue transplantation ameliorates PCOS by activating endogenous BAT, BAT transplantation is not applicable in clinic. Therefore, BAT activation with natural compound could be an effective treatment strategy for PCOS patients...
April 22, 2017: Journal of Nutritional Biochemistry
https://www.readbyqxmd.com/read/28501497/the-micro-managing-fat-exosomes-as-a-new-messenger
#13
Xiao-Wei Chen, Siming Li, Jiandie D Lin
Brown fat secretes endocrine factors and exerts metabolic effects beyond thermogenesis. In addition to protein factors and bioactive lipids, recent work has revealed brown fat-derived miRNAs carried by exosomes as a new means of interorgan crosstalk, with potentially important implications for metabolic physiology and disease.
May 10, 2017: Trends in Endocrinology and Metabolism: TEM
https://www.readbyqxmd.com/read/28494871/mirna-32-drives-brown-fat-thermogenesis-and-trans-activates-subcutaneous-white-fat-browning-in-mice
#14
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/28489156/impact-of-free-thyroxine-levels-and-other-clinical-factors-on-bare-metal-stent-restenosis
#15
Uğur Canpolat, Osman Turak, Fırat Özcan, Fatih Öksüz, Mehmet Ali Mendi, Çağrı Yayla, Sinan Aydoğdu
Objective: Thyroid hormones have both direct and indirect effects on thermogenesis such as modulating vascular smooth muscle cell proliferation. However, the influence of more subtle changes in thyroid hormones on coronary atherosclerosis remains a matter of speculation. Smooth muscle cells play a crucial role in the pathogenesis of in-stent restenosis (ISR). However, the relationship between free thyroxine (fT4) and ISR has not been studied. In the present study, we aimed to assess the role of preprocedural serum fT4 level on the development of ISR in patients undergoing coronary bare metal stent (BMS) implantation...
March 2017: Archives of Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28487438/the-niemann-pick-c1-gene-interacts-with-a-high-fat-diet-to-promote-weight-gain-through-differential-regulation-of-central-energy-metabolism-pathways
#16
Joseph J Castillo, David Jelinek, Hao Wei, Nicholas P Gannon, Roger A Vaughan, L John Horwood, F John Meaney, Randi Garcia-Smith, Kristina A Trujillo, Randall A Heidenreich, David Meyre, Robert A Orlando, Renee C LeBoeuf, William S Garver
A genome-wide association study (GWAS) reported that common variation in the human Niemann-Pick C1 gene (NPC1) is associated with morbid adult obesity. This study was confirmed using our BALB/cJ Npc1 mouse model, whereby heterozygous mice (Npc1(+/-)) with decreased gene dosage were susceptible to weight gain when fed a high-fat diet (HFD) compared to homozygous normal mice (Npc1(+/+)) fed the same diet. The objective for our current study was to validate this Npc1 gene-diet interaction using statistical modeling with fitted growth trajectories, conduct body weight analyses for different measures, and define the physiological basis responsible for weight gain...
May 9, 2017: American Journal of Physiology. Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28484396/nesfatin-1-in-the-lateral-parabrachial-nucleus-inhibits-food-intake-modulates-excitability-of-glucosensing-neurons-and-enhances-ucp1-expression-in-brown-adipose-tissue
#17
Jun-Hua Yuan, Xi Chen, Jing Dong, Di Zhang, Kun Song, Yue Zhang, Guang-Bo Wu, Xi-Hao Hu, Zheng-Yao Jiang, Peng Chen
Nesfatin-1, an 82-amino acid neuropeptide, has been shown to induce anorexia and energy expenditure. Food intake is decreased in ad libitum-fed rats following injections of nesfatin-1 into the lateral, third, or fourth ventricles of the brain. Although the lateral parabrachial nucleus (LPBN) is a key regulator of feeding behavior and thermogenesis, the role of nesfatin-1 in this structure has not yet been delineated. We found that intra-LPBN microinjections of nesfatin-1 significantly reduced nocturnal cumulative food intake and average meal sizes without affecting meal numbers in rats...
2017: Frontiers in Physiology
https://www.readbyqxmd.com/read/28481291/inflammation-downregulates-ucp1-expression-in-brown-adipocytes-potentially-via-sirt1-and-dbc1-interaction
#18
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/28469146/optical-visualisation-of-thermogenesis-in-stimulated-single-cell-brown-adipocytes
#19
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/28465400/the-significance-of-beige-and-brown-fat-in-humans
#20
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
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