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https://www.readbyqxmd.com/read/28432282/loss-of-function-myostatin-mutation-increases-insulin-sensitivity-and-browning-of-white-fat-in-meishan-pigs
#1
Chunbo Cai, Lili Qian, Shengwang Jiang, Youde Sun, Qingqing Wang, Dezun Ma, Gaojun Xiao, Biao Li, Shanshan Xie, Ting Gao, Yaoxing Chen, Jie Liu, Xiaorong An, Wentao Cui, Kui Li
Myostatin-deficient mice showed a remarkable hypertrophy of skeletal muscle, with a decreased fat mass and enhanced insulin sensitivity. Currently, it is unclear if the inhibition of myostatin could be used as an approach to treat human obesity and insulin resistance. In this study, we investigated if the inhibition of porcine myostatin has any effect on fat deposition and insulin sensitivity using genetically engineered Meishan pigs containing a myostatin loss-of-function mutation (Mstn -/- ). Our results indicated that, when compared with wild-type pigs, the amount of subcutaneous fat and leaf fat of Mstn -/- pigs were significantly decreased mainly due to the browning of subcutaneous adipose tissue...
April 4, 2017: Oncotarget
https://www.readbyqxmd.com/read/28431377/metabolic-regulation-and-the-anti-obesity-perspectives-of-human-brown-fat
#2
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/28431116/ontogeny-and-thermogenic-role-for-sternal-fat-in-female-sheep
#3
Belinda A Henry, Mark Pope, Mark Birtwistle, Rachael Loughnan, Reham Alagal, John-Paul Fuller-Jackson, Viv Perry, Helen Budge, Iain J Clarke, Michael E Symonds
Brown adipose tissue acting through a unique uncoupling protein (UCP1) has a critical role in preventing hypothermia in new-born sheep but is then considered to rapidly disappear during postnatal life. The extent to which the anatomical location of fat influences postnatal development and thermogenic function, particularly following feeding, in adulthood, are not known and were both examined in our study. Changes in gene expression of functionally important pathways (i.e. thermogenesis, development, adipogenesis and metabolism) were compared between sternal and retroperitoneal fat depots together with a representative skeletal muscle over the first month of postnatal life, coincident with the loss of brown fat and accumulation of white fat...
April 19, 2017: Endocrinology
https://www.readbyqxmd.com/read/28428261/ebf2-transcriptionally-regulates-brown-adipogenesis-via-the-histone-reader-dpf3-and-the-baf-chromatin-remodeling-complex
#4
Suzanne N Shapira, Hee-Woong Lim, Sona Rajakumari, Alexander P Sakers, Jeff Ishibashi, Matthew J Harms, Kyoung-Jae Won, Patrick Seale
The transcription factor early B-cell factor 2 (EBF2) is an essential mediator of brown adipocyte commitment and terminal differentiation. However, the mechanisms by which EBF2 regulates chromatin to activate brown fat-specific genes in adipocytes were unknown. ChIP-seq (chromatin immunoprecipitation [ChIP] followed by deep sequencing) analyses in brown adipose tissue showed that EBF2 binds and regulates the activity of lineage-specific enhancers. Mechanistically, EBF2 physically interacts with the chromatin remodeler BRG1 and the BAF chromatin remodeling complex in brown adipocytes...
April 20, 2017: Genes & Development
https://www.readbyqxmd.com/read/28425851/altered-structure-and-function-of-adipose-tissue-in-long-lived-mice-with-growth-hormone-related-mutations
#5
Justin Darcy, Samuel McFadden, Andrzej Bartke
A major focus of biogerontology is elucidating the role(s) of the endocrine system in aging and the accumulation of age-related diseases. Endocrine control of mammalian longevity was first reported in Ames dwarf (Prop1(df)) mice, which are long-lived due to a recessive Prop1 loss-of-function mutation resulting in deficiency of growth hormone (GH), thyroid-stimulating hormone, and prolactin. Following this report, several other GH-related mutants with altered longevity have been described including long-lived Snell dwarf and growth hormone receptor knockout mice, and short-lived GH overexpressing transgenic mice...
March 21, 2017: Adipocyte
https://www.readbyqxmd.com/read/28424466/the-role-of-the-brown-adipose-tissue-in-%C3%AE-3-adrenergic-receptor-activation-induced-sleep-metabolic-and-feeding-responses
#6
Éva Szentirmai, Levente Kapás
Brown adipose tissue (BAT) is regulated by the sympathetic nervous system via β3-adrenergic receptors (β3-AR). Here we tested the hypothesis that pharmacological stimulation of β3-ARs leads to increased sleep in mice and if this change is BAT dependent. In wild-type (WT) animals, administration of CL-316,243, a selective β3-AR agonist, induced significant increases in non-rapid-eye movement sleep (NREMS) lasting for 4-10 h. Simultaneously, electroencephalographic slow-wave activity (SWA) was significantly decreased and body temperature was increased with a delay of 5-6 h...
April 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28424263/the-kielin-chordin-like-protein-kcp-attenuates-high-fat-diet-induced-obesity-and-metabolic-syndrome-in-mice
#7
Abdul Soofi, Katherine I Wolf, Margo P Emont, Nathan Qi, Gabriel Martinez-Santibanez, Edward Grimley, Wesam Ostwani, Gregory R Dressler
Obesity and its associated complications, such as insulin resistance and non-alcoholic fatty liver disease, are reaching epidemic proportions. In mice, the TGF-beta superfamily is implicated in the regulation of white and brown adipose tissue differentiation. The Kielin/chordin-like Protein (KCP) is a secreted regulator of the TGF-beta superfamily pathways that can inhibit both TGF-beta and activin signals while enhancing bone morphogenetic protein (BMP) signaling. However, KCP's effects on metabolism and obesity have not been studied in animal models...
April 19, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28422755/%C3%AE-klotho-deficiency-protects-against-obesity-through-a-crosstalk-between-liver-microbiota-and-brown-adipose-tissue
#8
Emmanuel Somm, Hugues Henry, Stephen J Bruce, Sébastien Aeby, Marta Rosikiewicz, Gerasimos P Sykiotis, Mohammed Asrih, François R Jornayvaz, Pierre Damien Denechaud, Urs Albrecht, Moosa Mohammadi, Andrew Dwyer, James S Acierno, Kristina Schoonjans, Lluis Fajas, Gilbert Greub, Nelly Pitteloud
β-Klotho (encoded by Klb) is the obligate coreceptor mediating FGF21 and FGF15/19 signaling. Klb-/- mice are refractory to beneficial action of pharmacological FGF21 treatment including stimulation of glucose utilization and thermogenesis. Here, we investigated the energy homeostasis in Klb-/- mice on high-fat diet in order to better understand the consequences of abrogating both endogenous FGF15/19 and FGF21 signaling during caloric overload. Surprisingly, Klb-/- mice are resistant to diet-induced obesity (DIO) owing to enhanced energy expenditure and BAT activity...
April 20, 2017: JCI Insight
https://www.readbyqxmd.com/read/28420089/suppression-of-ghs-r-in-agrp-neurons-mitigates-diet-induced-obesity-by-activating-thermogenesis
#9
Chia-Shan Wu, Odelia Y N Bongmba, Jing Yue, Jong Han Lee, Ligen Lin, Kenji Saito, Geetali Pradhan, De-Pei Li, Hui-Lin Pan, Allison Xu, Shaodong Guo, Yong Xu, Yuxiang Sun
Ghrelin, an orexigenic hormone released primarily from the gut, signals the hypothalamus to stimulate growth hormone release, enhance appetite and promote weight gain. The ghrelin receptor, aka Growth Hormone Secretagogue Receptor (GHS-R), is highly expressed in the brain, with highest expression in Agouti-Related Peptide (AgRP) neurons of the hypothalamus. We recently reported that neuron-specific deletion of GHS-R completely prevents diet-induced obesity (DIO) in mice by activating non-shivering thermogenesis...
April 14, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28417872/brown-adipose-tissue-and-browning-more-than-just-a-heating-device
#10
Rubén Cereijo, David Sánchez-Infantes
No abstract text is available yet for this article.
April 2017: Endocrinol Diabetes Nutr
https://www.readbyqxmd.com/read/28414465/topical-intestinal-aminoimidazole-agonists-of-g-protein-coupled-bile-acid-receptor-1-promote-glucagon-like-peptide-1-secretion-and-improve-glucose-tolerance
#11
Manuel Lasalle, Vanessa Hoguet, Nathalie Hennuyer, Florence Leroux, Catherine Piveteau, Loic Belloy, Sophie Lestavel, Emmanuelle Vallez, Emilie Dorchies, Isabelle Duplan, Emmanuel Sevin, Maxime Culot, Fabien Gosselet, Rajaa Boulahjar, Adrien Herledan, Bart Staels, Benoit Deprez, Anne Tailleux, Julie Charton
The role of the G-Protein-coupled Bile Acid Receptor TGR5 in various organs, tissues and cell types, specifically in intestinal endocrine L-cells and brown adipose tissue, has made it a promising therapeutical target in several diseases, especially type-2 diabetes and metabolic syndrome. However, recent studies have shown deleterious on-target effects of systemic TGR5 agonists. To avoid these systemic effects while stimulating Glucagon Like Peptide-1 (GLP-1) secreting enteroendocrine L-cells, we have designed TGR5 agonists with low intestinal permeability...
April 17, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28414329/alternatively-activated-macrophages-do-not-synthesize-catecholamines-or-contribute-to-adipose-tissue-adaptive-thermogenesis
#12
Katrin Fischer, Henry H Ruiz, Kevin Jhun, Brian Finan, Douglas J Oberlin, Verena van der Heide, Anastasia V Kalinovich, Natasa Petrovic, Yochai Wolf, Christoffer Clemmensen, Andrew C Shin, Senad Divanovic, Frank Brombacher, Elke Glasmacher, Susanne Keipert, Martin Jastroch, Joachim Nagler, Karl-Werner Schramm, Dasa Medrikova, Gustav Collden, Stephen C Woods, Stephan Herzig, Dirk Homann, Steffen Jung, Jan Nedergaard, Barbara Cannon, Matthias H Tschöp, Timo D Müller, Christoph Buettner
Adaptive thermogenesis is the process of heat generation in response to cold stimulation. It is under the control of the sympathetic nervous system, whose chief effector is the catecholamine norepinephrine (NE). NE enhances thermogenesis through β3-adrenergic receptors to activate brown adipose tissue and by 'browning' white adipose tissue. Recent studies have reported that alternative activation of macrophages in response to interleukin (IL)-4 stimulation induces the expression of tyrosine hydroxylase (TH), a key enzyme in the catecholamine synthesis pathway, and that this activation provides an alternative source of locally produced catecholamines during the thermogenic process...
April 17, 2017: Nature Medicine
https://www.readbyqxmd.com/read/28414326/mesenchymal-stem-cells-in-obesity-insights-for-translational-applications
#13
Kenichi Matsushita, Victor J Dzau
Obesity is now a major public health problem worldwide. Lifestyle modification to reduce the characteristic excess body adiposity is important in the treatment of obesity, but effective therapeutic intervention is still needed to control what has become an obesity epidemic. Unfortunately, many anti-obesity drugs have been withdrawn from market due to adverse side effects. Bariatric surgery therefore remains the most effective therapy for severe cases, although such surgery is invasive and researchers continue to seek new control strategies for obesity...
April 17, 2017: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/28414270/human-biallelic-mfn2-mutations-induce-mitochondrial-dysfunction-upper-body-adipose-hyperplasia-and-suppression-of-leptin-expression
#14
Nuno M Rocha, David A Bulger, Andrea Frontini, Hannah Titheradge, Sigrid Bjerge Gribsholt, Rachel Knox, Matthew Page, Julie Harris, Felicity Payne, Claire Adams, Alison Sleigh, John Crawford, Anette Prior Gjesing, Jette Bork-Jensen, Oluf Pedersen, Inês Barroso, Torben Hansen, Helen Cox, Mary Reilly, Alex Rossor, Rebecca J Brown, Simeon I Taylor, Duncan McHale, Martin Armstrong, Elif A Oral, Vladimir Saudek, Stephen I O'Rahilly, Eamonn R Maher, Bjørn Richelsen, David B Savage, Robert K Semple
MFN2 encodes mitofusin 2, a membrane-bound mediator of mitochondrial membrane fusion and inter-organelle communication. MFN2 mutations cause axonal neuropathy, with associated lipodystrophy only occasionally noted, however homozygosity for the p.Arg707Trp mutation was recently associated with upper body adipose overgrowth. We describe similar massive adipose overgrowth with suppressed leptin expression in four further patients with biallelic MFN2 mutations and at least one p.Arg707Trp allele. Overgrown tissue was composed of normal-sized, UCP1-negative unilocular adipocytes, with mitochondrial network fragmentation, disorganised cristae, and increased autophagosomes...
April 17, 2017: ELife
https://www.readbyqxmd.com/read/28412531/vagus-nerve-is-involved-in-the-changes-in-body-temperature-induced-by-intragastric-administration-of-1-8-cineole-via-trpm8-in-mice
#15
Tomomi Urata, Noriyuki Mori, Tsutomu Fukuwatari
Transient Receptor Potential Melastatin 8 (TRPM8) is a cold receptor activated by mild cold temperature (<28°C). TRPM8 expressed in cutaneous sensory nerves is involved in cold sensation and thermoregulation. TRPM8 mRNA is detected in various tissues, including the gastrointestinal mucosa, and in the vagal afferent nerve. The relationship between vagal afferent nerve-specific expression of TRPM8 and thermoregulation remains unclear. In this study, we aimed to investigate whether TRPM8 expression in the vagal afferent nerve is involved in autonomic thermoregulation...
April 12, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/28412321/egcg-ameliorates-diet-induced-metabolic-syndrome-associating-with-the-circadian-clock
#16
Yashi Mi, Guoyuan Qi, Rong Fan, Xiaohua Ji, Zhigang Liu, Xuebo Liu
In response to the daily light-dark (LD) cycle, organisms on Earth have evolved with the approximately 24-h endogenous oscillations to coordinate behavioral and physiological processes, including feeding, sleep, and metabolism homeostasis. Circadian desynchrony triggered by an energy-dense diet rich in fats and fructose is intimately connected with a series of metabolic disorders. Previous studies revealed that (-)-Epigallocatechin-3-gallate (EGCG) could mitigate metabolic misalignment; however, only a few reports have focused on its potential effect on directly manipulating circadian rhythms to ameliorate metabolic syndrome...
April 12, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28409694/immunohistochemical-localization-of-irisin-in-mole-rats-spalax-leucodon
#17
F M Gür, S Timurkaan, M H Yalcin, A Girgin, B Gençer Tarakçı
Irisin was first identified in skeletal muscle cells. It is an exercise protein that is secreted into the circulation; it causes conversion of white adipose tissue to brown adipose tissue. We investigated irisin immunoreactivity in mole rat (Spalax leucodon) tissues. We examined cerebellum, pituitary, heart, liver, pancreas, spleen, uterus, kidney and striated muscle in female adult mole rats. Tissues were processed, embedded in paraffin, sectioned at 5 μm and stained immunohistochemically for irisin. Irisin immunostaining was detected in the cytoplasm of stained cells; the cytoplasm of Purkinje cells was unstained...
April 14, 2017: Biotechnic & Histochemistry: Official Publication of the Biological Stain Commission
https://www.readbyqxmd.com/read/28408438/prdm16-represses-the-type-i-interferon-response-in-adipocytes-to-promote-mitochondrial-and-thermogenic-programing
#18
Megan Kissig, Jeff Ishibashi, Matthew J Harms, Hee-Woong Lim, Rachel R Stine, Kyoung-Jae Won, Patrick Seale
Brown adipose has the potential to counteract obesity, and thus, identifying signaling pathways that regulate the activity of this tissue is of great clinical interest. PRDM16 is a transcription factor that activates brown fat-specific genes while repressing white fat and muscle-specific genes in adipocytes. Whether PRDM16 also controls other gene programs to regulate adipocyte function was unclear. Here, we identify a novel role for PRDM16 in suppressing type I interferon (IFN)-stimulated genes (ISGs), including Stat1, in adipocytes in vitro and in vivo Ectopic activation of type I IFN signaling in brown adipocytes induces mitochondrial dysfunction and reduces uncoupling protein 1 (UCP1) expression...
April 13, 2017: EMBO Journal
https://www.readbyqxmd.com/read/28408241/maternal-retinoids-increase-pdgfr%C3%AE-progenitor-population-and-beige-adipogenesis-in-progeny-by-stimulating-vascular-development
#19
Bo Wang, Xing Fu, Xingwei Liang, Zhixiu Wang, Qiyuan Yang, Tiande Zou, Wei Nie, Junxing Zhao, Pengfei Gao, Mei-Jun Zhu, Jeanene M de Avila, Joseph Maricelli, Buel D Rodgers, Min Du
Maternal vitamin A intake varies but its impact on offspring metabolic health is unknown. Here we found that maternal vitamin A or retinoic acid (RA) administration expanded PDGFRα(+) adipose progenitor population in progeny, accompanied by increased blood vessel density and enhanced brown-like (beige) phenotype in adipose tissue, protecting offspring from obesity. Blockage of retinoic acid signaling by either BMS493 or negative RA receptor (RARαDN) over-expression abolished the increase in blood vessel density, adipose progenitor population, and beige adipogenesis stimulated by RA...
April 4, 2017: EBioMedicine
https://www.readbyqxmd.com/read/28405341/diabetes-incidence-and-glucose-intolerance-prevalence-increase-with-higher-outdoor-temperature
#20
Lisanne L Blauw, N Ahmad Aziz, Martijn R Tannemaat, C Alexander Blauw, Anton J de Craen, Hanno Pijl, Patrick C N Rensen
OBJECTIVE: Rising global temperatures might contribute to the current worldwide diabetes epidemic, as higher ambient temperature can negatively impact glucose metabolism via a reduction in brown adipose tissue activity. Therefore, we examined the association between outdoor temperature and diabetes incidence in the USA as well as the prevalence of glucose intolerance worldwide. RESEARCH DESIGN AND METHODS: Using meta-regression, we determined the association between mean annual temperature and diabetes incidence during 1996-2009 for each US state separately...
2017: BMJ Open Diabetes Research & Care
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