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https://www.readbyqxmd.com/read/28424158/generation-of-a-multipurpose-prdm16-allele-by-targeted-trapping
#1
A Strassman, F Schnütgen, Q Dai, J C Jones, A C Gomez, L Pitstick, N E Holton, R Moskal, E R Leslie, H von Melchner, D R Beier, B C Bjork
Gene trap mutagenesis is a powerful tool to create loss-of-function mutations in mice and other model organisms. Modifications of traditional gene trap cassettes, including addition of conditional features in the form of Flip-excision (FlEx) arrays enabling directional gene trap cassette inversions by Cre and Flpe site-specific recombinases, greatly enhanced their experimental potential. By taking advantage of these conditional gene trap cassettes, we developed a generic strategy for generating conditional mutations and validated this strategy in mice carrying a multipurpose allele of the Prdm16 transcription factor gene...
April 19, 2017: Disease Models & Mechanisms
https://www.readbyqxmd.com/read/28408438/prdm16-represses-the-type-i-interferon-response-in-adipocytes-to-promote-mitochondrial-and-thermogenic-programing
#2
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/28397831/microrna-mir-23a-cluster-promotes-osteocyte-differentiation-by-regulating-tgf-%C3%AE-signalling-in-osteoblasts
#3
Huan-Chang Zeng, Yangjin Bae, Brian C Dawson, Yuqing Chen, Terry Bertin, Elda Munivez, Philippe M Campeau, Jianning Tao, Rui Chen, Brendan H Lee
Osteocytes are the terminally differentiated cell type of the osteoblastic lineage and have important functions in skeletal homeostasis. Although the transcriptional regulation of osteoblast differentiation has been well characterized, the factors that regulate differentiation of osteocytes from mature osteoblasts are poorly understood. Here we show that miR-23a∼27a∼24-2 (miR-23a cluster) promotes osteocyte differentiation. Osteoblast-specific miR-23a cluster gain-of-function mice have low bone mass associated with decreased osteoblast but increased osteocyte numbers...
April 11, 2017: Nature Communications
https://www.readbyqxmd.com/read/28358328/gelidium-elegans-regulates-the-ampk-prdm16-ucp-1-pathway-and-has-a-synergistic-effect-with-orlistat-on-obesity-associated-features-in-mice-fed-a-high-fat-diet
#4
Jia Choi, Kui-Jin Kim, Eun-Jeong Koh, Boo-Yong Lee
The incidence of obesity is rising at an alarming rate throughout the world and is becoming a major public health concern with incalculable social and economic costs. Gelidium elegans (GENS), also previously known as Gelidium amansii, has been shown to exhibit anti-obesity effects. Nevertheless, the mechanism by which GENS is able to do this remains unclear. In the present study, our results showed that GENS prevents high-fat diet (HFD)-induced weight gain through modulation of the adenosine monophosphate-activated protein kinase (AMPK)-PR domain-containing16 (PRDM16)-uncoupling protein-1 (UCP-1) pathway in a mice model...
March 30, 2017: Nutrients
https://www.readbyqxmd.com/read/28338809/resveratrol-derivative-btm-0512-mitigates-obesity-by-promoting-beige-remodeling-of-subcutaneous-preadipocytes
#5
Qingqing Li, Kuansong Wang, Yipeng Ma, Chunxiang Qin, Changsheng Dong, Ping Jin, Yan Wu, Xiaoming Xiong, Niansheng Li, Changping Hu, Jun Peng, Zhichun Yang
Recent studies revealed that sirtuin 1 (SIRT1) is involved in the regulation of energy metabolism and its agonist resveratrol showed anti-obesity effect. This study aims to determine whether BTM-0512, a novel derivative of resveratrol, acts as an antagonist of obesity and to explore its possible mechanisms. High-fat diet (HFD)-induced obese mice were intragastrically administered with BTM-0512 (5, 10, and 20 mg/kg/day) or resveratrol (10 mg/kg/day). It was found that the body weight, Lee's index, ratio of visceral adipose tissue (VAT) to body weight, and blood glucose were significantly reduced in BTM-0512-treated mice when compared with those in mice treated with resveratrol...
February 24, 2017: Acta Biochimica et Biophysica Sinica
https://www.readbyqxmd.com/read/28324027/follistatin-targets-distinct-pathways-to-promote-brown-adipocyte-characteristics-in-brown-and-white-adipose-tissues
#6
Rajan Singh, Melissa Braga, Srinivasa T Reddy, Se-Jin Lee, Meher Parveen, Victor Grijalva, Laurent Vergnes, Shehla Pervin
We previously demonstrated that Fst expression is highest in brown adipose tissue (BAT) and skeletal muscle, but is also present at substantial levels in epididymal (Epi) and subcutaneous (SC) white adipose tissues (WAT). Fst promotes mouse brown preadipocyte differentiation and promotes browning during differentiation of mouse embryonic fibroblasts (MEFs). Fst-transgenic (Fst-Tg) mouse show significant increase in circulating Fst levels and increased brown adipose mass. BAT of Fst-Tg mice had increased expression of brown adipose-associated markers including uncoupling protein 1 (UCP1), PRDM16, PGC-1α and Glut4...
January 16, 2017: Endocrinology
https://www.readbyqxmd.com/read/28288167/erythropoietin-epo-ameliorates-obesity-and-glucose-homeostasis-by-promoting-thermogenesis-and-endocrine-function-of-classical-brown-adipose-tissue-bat-in-diet-induced-obese-mice
#7
Kazuki Kodo, Satoru Sugimoto, Hisakazu Nakajima, Jun Mori, Ikuyo Itoh, Shota Fukuhara, Keiichi Shigehara, Taichiro Nishikawa, Kitaro Kosaka, Hajime Hosoi
Erythropoietin (EPO), clinically used as a hematopoietic drug, has received much attention due to its nonhematopoietic effects. EPO reportedly has beneficial effects on obesity and diabetes mellitus. We investigated whether interscapular brown adipose tissue (iBAT: main part of classical BAT) could play a role in EPO's anti-obesity and anti-diabetic effects in diet-induced obese mice. Four-week-old male C57BL/6J mice were fed a high-fat diet (HFD-Con), and half were additionally given an intraperitoneal injection of recombinant human EPO (200 IU/kg) (HFD-EPO) thrice a week for four weeks...
2017: PloS One
https://www.readbyqxmd.com/read/28270523/id1-promotes-obesity-by-suppressing-brown-adipose-thermogenesis-and-white-adipose-browning
#8
Mallikarjun Patil, Bal Krishan Sharma, Sawsan Elattar, Judith Chang, Shweta Kapil, Jinling Yuan, Ande Satyanarayana
Obesity results from increased energy intake or defects in energy expenditure. Brown adipose tissue (BAT) is specialized for energy expenditure, a process called adaptive thermogenesis. Peroxisome proliferator activated receptor γ coactivator 1α (PGC1α) controls BAT-mediated thermogenesis by regulating the expression of Ucp1 Inhibitor of differentiation 1 (Id1) is a helix-loop-helix transcription factor that plays important roles in cell proliferation and differentiation. Here, we demonstrate a novel function of Id1 in BAT thermogenesis and programming of beige adipocytes in white adipose tissue (WAT)...
March 7, 2017: Diabetes
https://www.readbyqxmd.com/read/28260165/l-arginine-promotes-protein-synthesis-and-cell-growth-in-brown-adipocyte-precursor-cells-via-the-mtor-signal-pathway
#9
Xi Ma, Meng Han, Defa Li, Shengdi Hu, Kyler R Gilbreath, Fuller W Bazer, Guoyao Wu
L-Arginine has been reported to enhance brown adipose tissue developments in fetal lambs of obese ewes, but the underlying mechanism is unknown. The present study tested the hypothesis that L-arginine stimulates growth and development of brown adipocyte precursor cells (BAPCs) through activation of mammalian target of rapamycin cell signaling. BAPCs isolated from fetal lambs at day 90 of gestation were incubated   for 6 h in arginine-free DMEM, and then cultured in DMEM with concentrations of 50, 100, 200, 500 or 1000 μmol L-arginine/L for 24-96 h...
March 4, 2017: Amino Acids
https://www.readbyqxmd.com/read/28239649/switching-harmful-visceral-fat-to-beneficial-energy-combustion-improves-metabolic-dysfunctions
#10
Xiaoyan Yang, Wenhai Sui, Meng Zhang, Mei Dong, Sharon Lim, Takahiro Seki, Ziheng Guo, Carina Fischer, Huixia Lu, Cheng Zhang, Jianmin Yang, Meng Zhang, Yangang Wang, Caixia Cao, Yanyan Gao, Xingguo Zhao, Meili Sun, Yuping Sun, Rujie Zhuang, Nilesh J Samani, Yun Zhang, Yihai Cao
Visceral fat is considered the genuine and harmful white adipose tissue (WAT) that is associated to development of metabolic disorders, cardiovascular disease, and cancer. Here, we present a new concept to turn the harmful visceral fat into a beneficial energy consumption depot, which is beneficial for improvement of metabolic dysfunctions in obese mice. We show that low temperature-dependent browning of visceral fat caused decreased adipose weight, total body weight, and body mass index, despite increased food intake...
February 23, 2017: JCI Insight
https://www.readbyqxmd.com/read/28212671/an-adaptive-variant-of-trib2-rs1057001-is-associated-with-higher-expression-levels-of-thermogenic-genes-in-human-subcutaneous-and-visceral-adipose-tissues
#11
Kazuhiro Nakayama, Sadahiko Iwamoto
BACKGROUND: An obesity-related single-nucleotide polymorphism (SNP) of the Tribbles pseudokinase 2 gene (TRIB2) was shown to have underwent adaptive evolution in the last glacial period, suggesting a selective advantage of this SNP in human populations in cold environments. In order to verify this hypothesis, the effect of the TRIB2 SNP on the expression of genes involved in adaptive thermogenesis was tested using messenger RNAs prepared from adipose tissues of Japanese adults. METHODS: Complementary DNA was prepared from subcutaneous adipose tissues (SAT) and visceral adipose tissues (VAT) obtained from 48 Japanese adults...
February 17, 2017: Journal of Physiological Anthropology
https://www.readbyqxmd.com/read/28186086/hoxc10-suppresses-browning-of-white-adipose-tissues
#12
Yvonne Ng, Shi-Xiong Tan, Sook Yoong Chia, Hwee Yim Angeline Tan, Sin Yee Gun, Lei Sun, Wanjin Hong, Weiping Han
Given that increased thermogenesis in white adipose tissue, also known as browning, promotes energy expenditure, significant efforts have been invested to determine the molecular factors involved in this process. Here we show that HOXC10, a homeobox domain-containing transcription factor expressed in subcutaneous white adipose tissue, is a suppressor of genes involved in browning white adipose tissue. Ectopic expression of HOXC10 in adipocytes suppresses brown fat genes, whereas the depletion of HOXC10 in adipocytes and myoblasts increases the expression of brown fat genes...
February 10, 2017: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/28140654/genome-wide-methylation-analysis-identifies-novel-cpg-loci-for-perimembranous-ventricular-septal-defects-in-human
#13
Kim Pj Wijnands, Jun Chen, Liming Liang, Michael Mpj Verbiest, Xihong Lin, Willem A Helbing, Adriana C Gittenberger-de Groot, Peter J van der Spek, André G Uitterlinden, Régine Pm Steegers-Theunissen
AIM: Congenital heart diseases are the most common birth defects worldwide and leading cause of infant mortality. The perimembranous ventricular septal defect is most prevalent. Epigenetics may provide an underlying mechanism of the gene-environment interactions involved. MATERIALS & METHODS: We examined epigenome-wide DNA methylation using the Illumina HumanMethylation450 BeadChip in 84 case children and 196 control children. RESULTS: We identified differential methylation of a CpG locus (cg17001566) within the PRDM16 gene after Bonferroni correction (p = 9...
March 2017: Epigenomics
https://www.readbyqxmd.com/read/28127622/differential-methylation-of-genes-in-individuals-exposed-to-maternal-diabetes-in-utero
#14
Peng Chen, Paolo Piaggi, Michael Traurig, Clifton Bogardus, William C Knowler, Leslie J Baier, Robert L Hanson
AIMS/HYPOTHESIS: Individuals exposed to maternal diabetes in utero are more likely to develop metabolic and cardiovascular diseases later in life. This may be partially attributable to epigenetic regulation of gene expression. We performed an epigenome-wide association study to examine whether differential DNA methylation, a major source of epigenetic regulation, can be observed in offspring of mothers with type 2 diabetes during the pregnancy (OMD) compared with offspring of mothers with no diabetes during the pregnancy (OMND)...
January 26, 2017: Diabetologia
https://www.readbyqxmd.com/read/28117277/loss-of-myod-promotes-fate-transdifferentiation-of-myoblasts-into-brown-adipocytes
#15
Chao Wang, Weiyi Liu, Yaohui Nie, Mulan Qaher, Hannah Elizabeth Horton, Feng Yue, Atsushi Asakura, Shihuan Kuang
Brown adipose tissue (BAT) represents a promising agent to ameliorate obesity and other metabolic disorders. However, the abundance of BAT decreases with age and BAT paucity is a common feature of obese subjects. As brown adipocytes and myoblasts share a common Myf5 lineage origin, elucidating the molecular mechanisms underlying the fate choices of brown adipocytes versus myoblasts may lead to novel approaches to expand BAT mass. Here we identify MyoD as a key negative regulator of brown adipocyte development...
February 2017: EBioMedicine
https://www.readbyqxmd.com/read/28099124/browning-of-white-adipose-tissue-lessons-from-experimental-models
#16
Thereza Cristina Lonzetti Bargut, Vanessa Souza-Mello, Marcia Barbosa Aguila, Carlos Alberto Mandarim-de-Lacerda
Beige or brite (brown-in-white) adipocytes are present in white adipose tissue (WAT) and have a white fat-like phenotype that when stimulated acquires a brown fat-like phenotype, leading to increased thermogenesis. This phenomenon is known as browning and is more likely to occur in subcutaneous fat depots. Browning involves the expression of many transcription factors, such as PR domain containing 16 (PRDM16) and peroxisome proliferator-activated receptor (PPAR)-γ, and of uncoupling protein (UCP)-1, which is the hallmark of thermogenesis...
January 18, 2017: Hormone Molecular Biology and Clinical Investigation
https://www.readbyqxmd.com/read/28058730/multilocus-analysis-reveals-three-candidate-genes-for-chinese-migraine-susceptibility
#17
Xing-Kai An, Jie Fang, Zhen-Zhen Yu, Qing Lin, Cong-Xia Lu, Hong-Li Qu, Qi-Lin Ma
Several genome-wide association studies (GWASs) in Caucasian populations have identified 12 loci that are significantly associated with migraine. More evidence suggests that serotonin receptors are also involved in migraine pathophysiology. In the present study, a case-control study was conducted in a cohort of 581 migraine cases and 533 ethnically matched controls among a Chinese population. Eighteen polymorphisms from serotonin receptors and GWASs were selected, and genotyping was performed using a Sequenom MALDI-TOF mass spectrometry iPLEX platform...
January 6, 2017: Clinical Genetics
https://www.readbyqxmd.com/read/28046166/expression-of-uncoupling-protein-1-in-bovine-muscle-cells
#18
M A Abd Eldaim, O Hashimoto, H Ohtsuki, T Yamada, M Murakami, K Onda, R Sato, Y Kanamori, Y Qiao, S Tomonaga, T Matsui, M Funaba
Uncoupling protein 1 (Ucp1) is predominantly expressed in brown/beige adipocytes in mammals. Although myogenic cells have been suggested to commit to a brown adipocyte lineage through the induction of Prdm16 expression, Prdm16 is also expressed in skeletal muscle. Thus, we examined expression of Ucp1 in bovine myogenic cells. Considering that Ucp1 is a principle molecule that induces energy expenditure in brown/beige adipocytes, expression of Ucp1 is not preferable in beef cattle because of potential decrease in energy (fattening) efficiency...
December 2016: Journal of Animal Science
https://www.readbyqxmd.com/read/27993981/prdm16-is-crucial-for-progression-of-the-multipolar-phase-during-neural-differentiation-of-the-developing-neocortex
#19
Mayuko Inoue, Ryota Iwai, Hidenori Tabata, Daijiro Konno, Mariko Komabayashi-Suzuki, Chisato Watanabe, Hiroko Iwanari, Yasuhiro Mochizuki, Takao Hamakubo, Fumio Matsuzaki, Koh-Ichi Nagata, Ken-Ichi Mizutani
The precise control of neuronal migration and morphological changes during differentiation is essential for neocortical development. We hypothesized that the transition of progenitors through progressive stages of differentiation involves dynamic changes in levels of mitochondrial reactive oxygen species (mtROS), depending on cell requirements. We found that progenitors had higher levels of mtROS, but that these levels were significantly decreased with differentiation. The Prdm16 gene was identified as a candidate modulator of mtROS using microarray analysis, and was specifically expressed by progenitors in the ventricular zone...
February 1, 2017: Development
https://www.readbyqxmd.com/read/27982067/brown-adipogenic-potential-of-brown-adipocytes-and-peri-renal-adipocytes-from-human-embryo
#20
Nan-Nan Wu, Chuan-Hai Zhang, Hyuek-Jong Lee, Yan Ma, Xin Wang, Xiao-Juan Ma, Wei Ma, Dong Zhao, Ying-Mei Feng
Both brown adipocytes (BAC) and beige cells hold therapeutic potential for the treatment of metabolic disorders. Unfortunately, the amount and activity of these cells are limited in adults. Although BAC marker expression has been shown in peri-renal adipose tissues in children and adults, functional assessment is lacking. Furthermore, it is entirely unknown whether adipose progenitors are present in human embryo and able to give rise to BAC in situ during evolution. Therefore, adipose tissues in the interscapular and peri-renal regions were dissected from human embryo and subcutaneous white adipose tissues (sWAT) were obtained from an adult...
December 16, 2016: Scientific Reports
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