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| Open AccessCDK6 inhibits de novo lipogenesis in white adipose tissues but not in the liver
Obesity is a risk factor for diseases. Here, authors found that inhibition of cyclin-dependent kinase 6 increased de novo lipogenesis in the adipose tissues but not in the liver, which may provide a strategy to concur obesity-induced maladies.
- Alexander J. Hu
- , Wei Li
- & Miaofen G. Hu
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| Open AccessApoL6 associates with lipid droplets and disrupts Perilipin1-HSL interaction to inhibit lipolysis
Lipolysis in adipose tissue releases fatty acids during fasting. Here, authors show that ApoL6, a lipid droplet-associated protein, is specifically expressed in adipocytes upon feeding to inhibit lipolysis by directly interacting with Perilipin 1 to competitively inhibit Perilipin 1-HSL interaction.
- Yuhui Wang
- , Hai P. Nguyen
- & Hei S. Sul
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| Open AccessAdipose-targeted triiodothyronine therapy counteracts obesity-related metabolic complications and atherosclerosis with negligible side effects
Although thyroid hormone (TH) has anti-obesity potential, systemic administration of TH causes severe adverse effects without obvious weight loss. Here, the authors show that adipose tissue-targeted delivery of TH with liposomes is a safe and efficient strategy to treat obesity and its related complications in mice.
- Kang Chen
- , Lai Yee Cheong
- & Aimin Xu
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| Open AccessThe Hippo pathway links adipocyte plasticity to adipose tissue fibrosis
Adipose tissue fibrosis is connected to obesity-related metabolic dysfunction. Qiu and colleagues discover that the Hippo pathway acts as a molecular switch in the initiation and development of adipose tissue fibrosis upon TGFβ stimulation.
- Hongyu Shen
- , Xun Huang
- & Yifu Qiu
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| Open AccessBeiging of perivascular adipose tissue regulates its inflammation and vascular remodeling
Perivascular adipose tissue (PVAT) has been reported to undergo inflammatory changes in response to vascular injury. Here, the authors show that vascular injury induces the beiging (brown adipose tissue-like phenotype change) of PVAT, which fine-tunes inflammatory response as a protective mechanism.
- Yusuke Adachi
- , Kazutaka Ueda
- & Issei Komuro
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| Open AccessAdipocyte Gq signaling is a regulator of glucose and lipid homeostasis in mice
Obesity impairs regulation of adipocyte lipolysis, which contributes towards development of insulin resistance. Here the authors report that adipocyte Gq signaling functions as a regulator of lipolysis and systemic glucose and lipid homeostasis in mice, suggesting that agents able to stimulate this pathway may prove useful as antidiabetic drugs.
- Takefumi Kimura
- , Sai P. Pydi
- & Jürgen Wess
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| Open AccessMacrophages in epididymal adipose tissue secrete osteopontin to regulate bone homeostasis
Visceral adipose tissue secretes cytokines to regulate the homeostasis of organs. Here, the authors show that epididymal white adipose tissue-secreted osteopontin induces lipophagocytic mobilization of macrophages and promotes bone matrix degradation via activating osteoclasts.
- Bingyang Dai
- , Jiankun Xu
- & Ling Qin
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| Open AccessA propolis-derived small molecule ameliorates metabolic syndrome in obese mice by targeting the CREB/CRTC2 transcriptional complex
Disruption of CREB/CRTC2, a key gluconeogenic transcriptional complex, has been shown to ameliorate insulin resistance in mice. Here, the authors show that the inhibitor artipllin C and the synthetic compound A57, which presents with higher inhibitory activity, improve insulin sensitivity in obese mice by inhibiting CREB-CRTC2 interaction.
- Yaqiong Chen
- , Jiang Wang
- & Yi Liu
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Article
| Open AccessBMP8 and activated brown adipose tissue in human newborns
Brown adipose tissue (BAT) in infants has been studied for more than a century, however, the knowledge about its physiological features is limited. Here, the authors investigate the link between BAT thermogenesis and the regulation of temperature in human new-borns with non-invasive infrared thermography.
- Adela Urisarri
- , Ismael González-García
- & Miguel López
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| Open AccessSingle-cell transcriptional networks in differentiating preadipocytes suggest drivers associated with tissue heterogeneity
The origin of the heterogeneity of metabolic and inflammatory profiles exhibited by white adipocytes is little understood. Here, using scRNA-seq and computational methods, the authors show that differentiating preadipocytes exhibit gene expression differences and suggest underlying regulators.
- Alfred K. Ramirez
- , Simon N. Dankel
- & Simon Kasif
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Article
| Open AccessFGF6 and FGF9 regulate UCP1 expression independent of brown adipogenesis
Uncoupling protein-1 (UCP1) plays a central role in energy dissipation in brown adipose tissue. Here the authors show that FGF6 and FGF9 induce UCP1 expression in adipocytes and preadipocytes, via modulation of a transcriptional network that is dissociated from brown adipogenesis.
- Farnaz Shamsi
- , Ruidan Xue
- & Yu-Hua Tseng
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Article
| Open AccessSingle-cell analysis reveals fibroblast heterogeneity and myeloid-derived adipocyte progenitors in murine skin wounds
The diversity of fibroblasts contributing to wound healing is unclear. Here, the authors use single-cell RNA-sequencing to identify heterogeneity among murine fibroblasts in the wound and find that recruited myeloid cells contribute to adipocyte regeneration during healing.
- Christian F. Guerrero-Juarez
- , Priya H. Dedhia
- & Maksim V. Plikus
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Article
| Open AccessLsd1 regulates skeletal muscle regeneration and directs the fate of satellite cells
Satellite cells can differentiate both into myocytes and brown adipocytes. Here, the authors show that the histone demethylase Lsd1 prevents adipogenic differentiation of satellite cells by repressing expression of Glis1, and that its ablation changes satellite cell fate towards brown adipocytes and delays muscle regeneration in mice.
- Milica Tosic
- , Anita Allen
- & Roland Schüle
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Article
| Open AccessLkb1 controls brown adipose tissue growth and thermogenesis by regulating the intracellular localization of CRTC3
The kinase Lkb1 is expressed in various metabolic tissues and is known to regulate cellular and systemic energy homeostasis. Here, the authors delete Lkb1 specifically in mature adipocytes of mice to show that Lkb1 regulates brown adipose tissue expansion and expression of UCP1.
- Tizhong Shan
- , Yan Xiong
- & Shihuan Kuang
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| Open AccessSENP1-mediated NEMO deSUMOylation in adipocytes limits inflammatory responses and type-1 diabetes progression
Pro-inflammatory NF-κB signalling is regulated by protein sumoylation. Here the authors show that lack of the desumoylating protease SENP1 in fat tissue induces NF-κB activity and inflammation in peri-pancreatic adipocytes, leading to symptoms of type 1 diabetes in mice.
- Lan Shao
- , Huanjiao Jenny Zhou
- & Wang Min
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| Open AccessRegion-specific variation in the properties of skeletal adipocytes reveals regulated and constitutive marrow adipose tissues
Bone marrow contains adipocytes, which have been thought to form one type of marrow adipose tissue (MAT). Here, the authors identify two MAT subpopulations in mice and humans—‘regulated’ and ‘constitute’ MAT—which show distinct phenotypic and cellular traits, and respond differently to cold exposure.
- Erica L. Scheller
- , Casey R. Doucette
- & Ormond A. MacDougald
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| Open AccessSelective enhancement of insulin sensitivity in the mature adipocyte is sufficient for systemic metabolic improvements
Insulin resistance in adipose tissue is a hallmark of obesity. Here, the authors generate inducible adipocyte-specific PTEN knockout mice to demonstrate that enhanced insulin sensitivity in adipose tissue is directly linked to improved systemic metabolic homeostasis, despite an increase in fat mass.
- Thomas S. Morley
- , Jonathan Y. Xia
- & Philipp E. Scherer
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Cidea improves the metabolic profile through expansion of adipose tissue
Unlike rodents, humans produce the protein Cidea in white adipose tissue, where it associates with lipid droplets. Here the authors generate mice that express human Cidea in fat tissues to show Cidea exerts beneficial metabolic effects by regulating the expansion of visceral fat in response to a high-fat diet.
- Gustavo Abreu-Vieira
- , Alexander W. Fischer
- & Natasa Petrovic
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Pharmacological repression of PPARγ promotes osteogenesis
Central to the lineage commitment of multipotent mesenchymal stem cells is the nuclear receptor PPARγ, the master regulator of adipogenesis. Here the authors use a variety of structural approaches to rationally design PPARγ inverse agonist SR2595, and demonstrate its ability to promote osteogenesis.
- David P. Marciano
- , Dana S. Kuruvilla
- & Patrick R. Griffin
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| Open AccessStimulation of soluble guanylyl cyclase protects against obesity by recruiting brown adipose tissue
The enzyme soluble guanylyl cyclase (sGC) regulates differentiation of brown fat. Here, Hoffman et al.show that a small molecule sGC stimulator increases brown fat activity and browning of white fat, thereby inducing energy expenditure, weight loss and partial protection from diet-induced obesity in mice.
- Linda S. Hoffmann
- , Jennifer Etzrodt
- & Alexander Pfeifer
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| Open AccessJMJD1A is a signal-sensing scaffold that regulates acute chromatin dynamics via SWI/SNF association for thermogenesis
Demethylase JMJD1A activates thermogenesis-related target genes in response to β-adrenergic hormones. Here, the authors show that phosphorylation of JMJD1A at S265 increases its interaction with the SWI/SNF chromatin remodeler, leading to long-range chromatin interactions and target gene activation.
- Yohei Abe
- , Royhan Rozqie
- & Juro Sakai
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| Open AccessFTO influences adipogenesis by regulating mitotic clonal expansion
Mutations in the FTO gene have been linked to obesity. Here, Merkestein et al. provide in vitro and in vivo evidence that FTOdirectly regulates adipogenesis in mice at the stage of mitotic clonal expansion, likely by modulating the expression of the transcription factor RUNX1T1.
- Myrte Merkestein
- , Samantha Laber
- & Roger D. Cox
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Berberine activates thermogenesis in white and brown adipose tissue
Berberine is contained in some plant-derived medicines and is known to have anti-diabetic effects. Here the authors show that berberine activates thermogenesis in white and brown adipose tissues, thereby increasing organismal energy expenditure and limiting weight gain in genetically obese mice.
- Zhiguo Zhang
- , Huizhi Zhang
- & Guang Ning
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Adipocytes arise from multiple lineages that are heterogeneously and dynamically distributed
Myf5 lineage precursor cells give rise to brown adipocytes. Here, the authors show that the Myf5 lineage, as well as the Pax3 lineage, contribute to white and brite mature adipocytes and describe the effects of Myf5 lineage-specific deletion of the insulin receptor on adipose tissue formation in mice.
- Joan Sanchez-Gurmaches
- & David A. Guertin
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LSD1 promotes oxidative metabolism of white adipose tissue
Brown adipocytes are rich in mitochondria and influence whole-body energy balance. Here, Duteil et al. show that the lysine-specific demethylase 1 (LSD1) controls mitochondrial biogenesis and the formation of brown-like adipocytes, and that LSD1 overexpression in white fat reduces weight gain of mice on a high-fat diet.
- Delphine Duteil
- , Eric Metzger
- & Roland Schüle
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Intramuscular adipogenesis is inhibited by myo-endothelial progenitors with functioning Bmpr1a signalling
Bmp signalling is required for adult muscle maintenance and growth. Here, the authors show that ablating the expression of Bmp receptor 1a in mouse myo-endothelial cells increases intramuscular adipogenesis.
- Ping Huang
- , Tim J. Schulz
- & Emanuela Gussoni
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Regulation of MKL1 via actin cytoskeleton dynamics drives adipocyte differentiation
Adipocyte differentiation is accompanied by large scale changes in the actin cytoskeleton. Here, Nobusue et al.show that binding to G-actin sequesters the transcriptional coactivator MKL1 in the cytoplasm, and triggers differentiation by inducing the expression of pro-adipogenic transcription factor PPARγ.
- Hiroyuki Nobusue
- , Nobuyuki Onishi
- & Koichiro Kano
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Early adipogenesis is regulated through USP7-mediated deubiquitination of the histone acetyltransferase TIP60
Tip60 is a transcriptional coregulator that has an important role in differentiation. Here, Gao et al. demonstrate that the deubiquitination of Tip60 by USP7, a dominant deubiquitinating enzyme, is a key mechanism in early adipogenesis regulation.
- Yuan Gao
- , Arjen Koppen
- & Eric Kalkhoven
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A peptide probe for targeted brown adipose tissue imaging
Current methods to image brown adipose tissue rely on radioactive tracers and specialized imaging equipment. Here Azhdarinia et al.report a peptide-based probe that selectively binds to the vascular endothelium of brown adipose tissue and allows the near-infrared imaging of brown fat in mice.
- Ali Azhdarinia
- , Alexes C. Daquinag
- & Mikhail G. Kolonin