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Qingbo Chen, Lei Huang, Dongning Pan, Lihua J Zhu, Yong-Xu Wang
Transcriptional co-activator Prdm16 controls brown fat development and white fat browning, but how this thermogenic function is modulated post-translationally is poorly understood. Here, we report that Cbx4, a Polycomb group protein, is a SUMO E3 ligase for Prdm16 and that Cbx4-mediated sumoylation of Prdm16 is required for thermogenic gene expression. Cbx4 expression is enriched in brown fat and is induced in adipose tissue by acute cold exposure. Sumoylation of Prdm16 at lysine 917 by Cbx4 blocks its ubiquitination-mediated degradation, thereby augmenting its stability and thermogenic function...
March 13, 2018: Cell Reports
Sy-Ying Leu, Yung-Chieh Tsai, Wen-Chi Chen, Chih-Hsiung Hsu, Yen-Mei Lee, Pao-Yun Cheng
Promoting white adipose tissue (WAT) to acquire brown-like characteristics is a promising approach for obesity treatment. Although raspberry ketone (RK) has been reported to possess antiobesity activity, its effects on the formation of brown-like adipocytes remain unclear. Therefore, we investigated the effects and underlying mechanism of RK on WAT browning in 3T3-L1 adipocytes and rats with ovariectomy (Ovx)-induced obesity. RK (100 μM) significantly induced browning of 3T3-L1 cells by increasing mitochondrial biogenesis and the expression of browning-specific proteins (PR domain containing 16, PRDM16; peroxisome proliferator-activated receptor gamma coactivator 1-alpha, PGC-1α; uncoupling protein-1, UCP-1) and lipolytic enzymes (hormone-sensitive lipase and adipose triglyceride lipase)...
February 13, 2018: Journal of Nutritional Biochemistry
Verneri Anttila, Maija Wessman, Mikko Kallela, Aarno Palotie
Genetics of migraine has recently undergone a major shift, moving in the space of a few years from having only a few known genes for rare Mendelian forms to 47 known common variant loci affecting the susceptibility of the common forms of migraine. This has largely been achieved by rapidly increasing sample sizes for genomewide association studies (GWAS), soon to be followed by the first wave of large-scale exome-sequencing studies. The large number of detected loci, chief among them TRPM8, PRDM16, and LRP1, have enabled a number of in silico analyses, which have shed light on the functional and tissue-level aspects of the common risk variants for migraine, including evidence for involvement of both vascular and neuronal mechanisms...
2018: Handbook of Clinical Neurology
Khanh-Van Tran, Timothy Fitzgibbons, So Yun Min, Tiffany DeSouza, Silvia Corvera
OBJECTIVE: Perivascular adipose tissue depots around the aorta are regionally distinct and have specific functional properties. Thoracic aorta perivascular adipose tissue (tPVAT) expresses higher levels of thermogenic genes and lower levels of inflammatory genes than abdominal aorta perivascular adipose tissue (aPVAT). It is not known whether this distinction is due to the in-vivo functional environment or to cell-autonomous traits that persist outside the in-vivo setting. In this study, we asked whether the progenitor cells in tPVAT and aPVAT have cell-autonomous traits that lead to formation of regionally distinct PVAT...
January 10, 2018: Molecular Metabolism
Dominic S Ng
PURPOSE OF REVIEW: Lecithin cholesterol acyltyransferase (LCAT) deficiency is a rare monogenic disorder causing lipoprotein dysregulation and multiple organ dysfunctions, including renal impairment. LCAT knockout mice have been shown informative in elucidating mechanisms of many major clinical morbid phenotypes. Extended characterization of the LDL receptor/LCAT double knockout (Ldlr/Lcat-DKO or DKO) mice had led to the discovery of a number of novel protective metabolic phenotypes, including resistance to obesity, nonalcoholic steatohepatitis (NASH) and insulin resistance...
January 24, 2018: Current Opinion in Lipidology
Pamela A Long, Jared M Evans, Timothy M Olson
Dilated cardiomyopathy (DCM) is a heritable, genetically heterogeneous disorder characterized by progressive heart failure. DCM typically remains clinically silent until adulthood, yet symptomatic disease can develop in childhood. We sought to identify the genetic basis of pediatric DCM in 15 sporadic and three affected-siblings cases, comprised of 21 affected children (mean age, five years) whose parents had normal echocardiograms (mean age, 39 years). Twelve underwent cardiac transplantation and five died with severe heart failure...
August 8, 2017: Journal of Cardiovascular Development and Disease
Wenjing Wu, Jin Zhang, Chen Zhao, Yunmei Sun, Yajun Yin, Yongjia Peng, Weijun Pang, Gongshe Yang
The C1q/TNF-related protein 6 (CTRP6) is an adipokine involved in diverse biolgical processes. Formerly, we identified that CTRP6 regulates adipocyte differentiation, fatty acid oxidation and triglyceride accumulation in vitro. However, the effects of CTRP6 on adiposity in vivo have not yet been defined. This study aimed to confirm the involvement of CTRP6 in adipose accumulation and brown adipogenesis by intraperitoneal injection of the CTRP6-shRNA lentivirus into mice (CL mice). CL mice were significantly thinner than the control mice after feeding with a high fat diet (HFD), independent of food intake quantity...
January 20, 2018: Experimental Cell Research
Qian Li, Yue Hua, Yilin Yang, Xinyu He, Wei Zhu, Jiyong Wang, Xiaoqing Gan
Osteocalcin has recently been shown to regulate energy homeostasis through multiple pathways. Adipose tissue is a main organ of energy metabolism, and administration of recombinant osteocalcin in mice promoted energy consumption, thus counteracting obesity and glucose intolerance. The regulation of osteocalcin in islet β cells has been well documented; however, it is unknown whether osteocalcin can also act on adipocytes, and if does, how it functions. Here, we provided evidence to demonstrate a specific role for osteocalcin in brown adipocyte thermogenesis...
January 22, 2018: Molecular and Cellular Biology
P Subash-Babu, Ali A Alshatwi
Ononitol monohydrate (OMH), a glycoside was originally isolated from Cassia tora (Linn.). Glycosides regulate lipid metabolism but scientific validation desired. Hence, we aimed to evaluate the effect of OMH on enhancing mitochondrial potential, mitochondrial biogenesis, upregulate the expression of brown adipogenesis specific genes in maturing adipocytes. In addition, we observed the inter-relation between adipocyte and T-lymphocyte; whether, OMH treated adipocyte-condition medium stimulate T-cell chemokine linked with insulin resistance...
January 19, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Tamiris Lima Rachid, Flavia Maria Silva-Veiga, Francielle Graus-Nunes, Isabele Bringhenti, Carlos Alberto Mandarim-de-Lacerda, Vanessa Souza-Mello
BACKGROUND AND AIMS: Obesity compromises adipocyte physiology. PPARs are essential to adipocyte plasticity, but its isolated role in the browning phenomenon is not clear. This study aimed to examine whether activation of PPAR-α or PPAR-β/δ could induce beige cell depots in the subcutaneous white adipose tissue of diet-induced obese mice. MATERIAL AND METHODS: Sixty animals were randomly assigned to receive a control diet (C, 10% lipids) or a high-fat diet (HF, 50% lipids) for ten weeks...
2018: PloS One
Tong Xing, Yifei Kang, Xinglian Xu, Bo Wang, Min Du, Mei-Jun Zhu
SCOPE: Excessive lipid accumulation in white adipose tissue (WAT) leads to chronic inflammation and metabolic dysfunction. Raspberry (RB) contains high amount of polyphenols and dietary fibers. The objective of the study is to evaluate the effects of RB supplementation on WAT morphology, inflammation, and insulin signaling in high fat diet (HFD)-induced obese mice, and further explore the underlying mechanisms. METHODS AND RESULTS: C57BL/6J mice are fed with a control diet or a HFD supplemented with 0 or 5% freeze dried RB for 12 weeks...
January 10, 2018: Molecular Nutrition & Food Research
Jingyi Chi, Zhuhao Wu, Chan Hee J Choi, Lily Nguyen, Saba Tegegne, Sarah E Ackerman, Audrey Crane, François Marchildon, Marc Tessier-Lavigne, Paul Cohen
While the cell-intrinsic pathways governing beige adipocyte development and phenotype have been increasingly delineated, comparatively little is known about how beige adipocytes interact with other cell types in fat. Here, we introduce a whole-tissue clearing method for adipose that permits immunolabeling and three-dimensional profiling of structures including thermogenic adipocytes and sympathetic innervation. We found that tissue architecture and sympathetic innervation differ significantly between subcutaneous and visceral depots...
January 9, 2018: Cell Metabolism
Yutaka Hasegawa, Kenji Ikeda, Yong Chen, Diana L Alba, Daniel Stifler, Kosaku Shinoda, Takashi Hosono, Pema Maretich, Yangyu Yang, Yasushi Ishigaki, Jingyi Chi, Paul Cohen, Suneil K Koliwad, Shingo Kajimura
Adipose tissue fibrosis is a hallmark of malfunction that is linked to insulin resistance and type 2 diabetes; however, what regulates this process remains unclear. Here we show that the PRDM16 transcriptional complex, a dominant activator of brown/beige adipocyte development, potently represses adipose tissue fibrosis in an uncoupling protein 1 (UCP1)-independent manner. By purifying the PRDM16 complex, we identified GTF2IRD1, a member of the TFII-I family of DNA-binding proteins, as a cold-inducible transcription factor that mediates the repressive action of the PRDM16 complex on fibrosis...
January 9, 2018: Cell Metabolism
Xin-Hua Xiao, Xiao-Yan Qi, Ya-Di Wang, Li Ran, Jing Yang, Huan-Li Zhang, Can-Xin Xu, Ge-Bo Wen, Jiang-Hua Liu
Recent studies have highlighted recruiting and activating brite adipocytes in WAT (so-called "browning") would be an attractive anti-obesity strategy. Zinc alpha2 glycoprotein (ZAG) is reported to ameliorate glycolipid metabolism and lose body weight in obese mice. However whether the body reducing effect mediated by browning programme remains unclear. Here, we show that overexpression of ZAG in 3T3-L1 adipocytes enhanced expression of brown fat-specific markers (UCP-1, PRDM16 and CIDEA), mitochondrial biogenesis genes (PGC-1α, NRF-1/2 and mtTFA) and the key lipid metabolism lipases (ATGL, HSL, CPT1-A and p-acyl-CoA carboxylase)...
January 6, 2018: Biochemical and Biophysical Research Communications
Ashok Sharma, Xiang Liu, David Hadley, William Hagopian, Wei-Min Chen, Suna Onengut-Gumuscu, Carina Törn, Andrea K Steck, Brigitte I Frohnert, Marian Rewers, Anette-G Ziegler, Åke Lernmark, Jorma Toppari, Jeffrey P Krischer, Beena Akolkar, Stephen S Rich, Jin-Xiong She
Traditional linkage analysis and genome-wide association studies have identified HLA and a number of non-HLA genes as genetic factors for islet autoimmunity (IA) and type 1 diabetes (T1D). However, the relative risk associated with previously identified non-HLA genes is usually very small as measured in cases/controls from mixed populations. Genetic associations for IA and T1D may be more accurately assessed in prospective cohorts. In this study, 5806 subjects from the TEDDY (The Environmental Determinants of Diabetes in the Young) study, an international prospective cohort study, were genotyped for 176,586 SNPs on the ImmunoChip...
January 5, 2018: Journal of Autoimmunity
Nabil Rabhi, Sarah Anissa Hannou, Xavier Gromada, Elisabet Salas, Xi Yao, Frédérik Oger, Charlène Carney, Isabel C Lopez-Mejia, Emmanuelle Durand, Iandry Rabearivelo, Amélie Bonnefond, Emilie Caron, Lluis Fajas, Christian Dani, Philippe Froguel, Jean-Sébastien Annicotte
OBJECTIVES: Genome-wide association studies have reported that DNA polymorphisms at the CDKN2A locus modulate fasting glucose in human and contribute to type 2 diabetes (T2D) risk. Yet the causal relationship between this gene and defective energy homeostasis remains elusive. Here we sought to understand the contribution of Cdkn2a to metabolic homeostasis. METHODS: We first analyzed glucose and energy homeostasis from Cdkn2a-deficient mice subjected to normal or high fat diets...
December 1, 2017: Molecular Metabolism
Y Gao, N R Qimuge, J Qin, R Cai, X Li, G Y Chu, W J Pang, G S Yang
Piglets are characteristically cold intolerant and thus susceptible to high mortality. However, browning of white adipose tissue (WAT) can induce non-shivering thermogenesis as a potential strategy to facilitate the animal's response to cold. Whether cold exposure can induce browning of subcutaneous WAT (sWAT) in piglets in a similar manner as it can in humans remains largely unknown. In this study, piglets were exposed to acute cold (4°C, 10 h) or chronic cold exposure (8°C, 15 days), and the genes and proteins of uncoupling protein 1 (UCP1)-dependent and independent thermogenesis, mitochondrial biogenesis, lipogenic and lipolytic processes were analysed...
November 16, 2017: Animal: An International Journal of Animal Bioscience
Liuqing Yang, Weijie Zhang, Yanbo Wang, Tianhui Zou, Bin Zhang, Yuanyuan Xu, Taohong Pang, Qingqing Hu, Min Chen, Lei Wang, Ying Lv, Kai Yin, Hongwei Liang, Xi Chen, Guifang Xu, Xiaoping Zou
miR-214 is an important oncomiRNA and is upregulated in various types of cancer, including gastric cancer. However, the molecular mechanism underlying the ectopic expression and function of miR-214 in gastric cancer is largely undefined. In this study, we found that miR-214 induces the Warburg effect and promotes the migration and proliferation of human gastric cancer cells. According to the mechanistic analysis, miR-214 expression is induced by environmental hypoxia, and miR-214 mediates hypoxia-induced functions...
February 1, 2018: Cancer Letters
José María Moreno-Navarrete, Matteo Serino, Vincent Blasco-Baque, Vincent Azalbert, Richard H Barton, Marina Cardellini, Jèssica Latorre, Francisco Ortega, Mònica Sabater-Masdeu, Rémy Burcelin, Marc-Emmanuel Dumas, Wifredo Ricart, Massimo Federici, José Manuel Fernández-Real
SCOPE: To examine the potential relationship among gene expression markers of adipose tissue browning, gut microbiota and insulin sensitivity in humans. METHODS AND RESULTS: Gut microbiota composition and gene markers of browning were analysed in subcutaneous (SAT) and visceral (VAT) adipose tissue from morbidly obese subjects (n = 34). Plasma acetate was measured through (1) H NMR and insulin sensitivity using euglycemic hyperinsulinemic clamp. Subjects with insulin resistance showed an increase in the relative abundance (RA) of the phyla Bacteroidetes and Proteobacteria while RA of Firmicutes was decreased...
November 3, 2017: Molecular Nutrition & Food Research
S Rozenblit-Susan, N Chapnik, O Froy
BACKGROUND/OBJECTIVES: Serotonin is synthesized by many cells in the periphery to affect vasoconstriction, intestinal motility, and glucose and lipid metabolism. It has recently been shown that serotonin leads to fat accumulation in white adipose tissue (WAT). However, the direct effect of serotonin on brown adipose tissue differentiation and metabolism is limited. Therefore, our aim was to investigate the effect of serotonin on brown adipocyte metabolism and differentiation. METHODS: Non-differentiated HIB1B cells and differentiated HIB1B brown adipocytes were treated with serotonin and their metabolism and differentiation examined...
October 30, 2017: International Journal of Obesity: Journal of the International Association for the Study of Obesity
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