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Marin L Gantner, Bethany C Hazen, Elodie Eury, Erin L Brown, Anastasia Kralli
Brown adipose tissue (BAT) thermogenesis relies on a high abundance of mitochondria and the unique expression of the mitochondrial protein UCP1, which uncouples substrate oxidation from ATP synthesis. Adrenergic stimulation of brown adipocytes activates UCP1-mediated thermogenesis; it also induces the expression of Ucp1 and other genes important for thermogenesis, thereby endowing adipocytes with higher oxidative and uncoupling capacities. Adipocyte mitochondrial biogenesis and oxidative capacity are controlled by multiple transcription factors, including the estrogen-related receptor α (ERRα)...
October 20, 2016: Endocrinology
C Cortes-Oliveira, C F Nicoletti, M A de Souza Pinhel, B A P de Oliveira, D C G Quinhoneiro, N Y Noronha, J S Marchini, W A da Silva Júnior, W S Júnior, C B Nonino
BACKGROUND/OBJECTIVES: Although energy restriction contributes to weight loss, it may also reduce energy expenditure, limiting the success of weight loss in the long term. Studies have described how genetics contributes to the development of obesity, and uncoupling proteins 1 and 2 (UCP1 and UCP2) and beta-3-adrenoceptor (ADRB3) have been implicated in the metabolic pathways that culminate in this condition. This study aimed to evaluate how the UCP1, UCP2 and ADRB3 genes influence weight loss in severely obese women submitted to hypocaloric dietary intervention...
October 19, 2016: European Journal of Clinical Nutrition
Yuanting Cui, Li Li, Peng Gao, Liqun Ma, Daoyan Liu, Zhiming Zhu
OBJECTIVE: Obesity is global healthy problem. Uncoupling protein 1 (UCP1) mainly expresses on brown adipose tissue (BAT), uncouples energy substrate oxidation from mitochondrial ATP production and results in the loss of potential energy as heat. Transient receptor potential vanilloid subfamily, member 1 (TRPV1) is the heat-gated cation ion channel. The aim of this study was to investigate the in vivo role of TRPV1 and UCP1 co-action in obesity. DESIGN AND METHOD: We generated and characterized UCP1 mice lacking TRPV1 activity (TRPV1/UCP1 mice)...
September 2016: Journal of Hypertension
Andrzej M Woyda-Ploszczyca, Wieslawa Jarmuszkiewicz
Uncoupling proteins (UCPs) belong to the mitochondrial anion carrier protein family and mediate regulated proton leak across the inner mitochondrial membrane. Free fatty acids, aldehydes such as hydroxynonenal, and retinoids activate UCPs. However, there are some controversies about the effective action of retinoids and aldehydes alone; thus, only free fatty acids are commonly accepted positive effectors of UCPs. Conversely, purine nucleotides such as GTP inhibit UCP-mediated mitochondrial proton leak. In turn, membranous coenzyme Q may play a role as a redox state-dependent metabolic sensor that modulates the complete activation/inhibition of UCPs...
October 14, 2016: Biochimica et Biophysica Acta
Leonor Rodríguez-Sánchez, Eduardo Rial
The uncoupling protein UCP1 from brown adipose tissue is a mitochondrial carrier which allows dissipation of metabolic energy as heat. We have characterized the human UCP1 (HsUCP1) recombinantly expressed in Saccharomyces cerevisiae and we demonstrate that HsUCP1 is activated by fatty acids and retinoids in a nucleotide sensitive manner just as its rodent orthologs. However, in the absence of regulators, rodent UCP1 presents a high ohmic proton conductance that cannot be detected in HsUCP1. Since the human protein can be activated in a nucleotide sensitive manner, we conclude that it must have lost selectively the basal proton conductance...
October 14, 2016: Biochimie
D Löffler, K Landgraf, D Rockstroh, J T Schwartze, H Dunzendorfer, W Kiess, A Körner
BACKGROUND: Meteorin-like (METRNL) is a recently described circulating protein shown to be highly expressed in white adipose tissue and to beneficially affect energy metabolism in mice. OBJECTIVE: We systematically evaluated the role of METRNL for human adipogenesis and its association with obesity, browning and hyperinsulinemia in children. In addition, we assessed the functional relevance of METRNL for human adipogenesis. RESULTS: METRNL expression decreased during human adipocyte differentiation in vitro...
October 17, 2016: International Journal of Obesity: Journal of the International Association for the Study of Obesity
Xu Zhang, Qianni Cheng, Yixiang Wang, Po Sing Leung, Kinglun Kingston Mak
Bone plays a role in energy metabolism, but the interplay between bone and other organs in this process is not completely understood. Here, we show that upregulated Hh signaling in bones results in increased whole-body energy expenditure, white adipose tissue (WAT) browning, hypoglycemia and skeletal muscle atrophy. We found that Hh signaling induces PTHrP secretion from bones and causes WAT browning. Injection of PTHrP-neutralizing antibody attenuates WAT browning and improves the circulating blood glucose level while high-fat diet treatment only rescues hypoglycemia...
October 14, 2016: Cell Death and Differentiation
Ziye Xu, Jiaqi Liu, Tizhong Shan
Adipose tissues regulate energy metabolism and reproduction. There are three types of adipocytes (brown, white and beige adipocytes) in mammals. White adipocytes store energy and are closely associated with obesity and other metabolic diseases. The beige and brown adipocytes have numerous mitochondria and high levels of UCP1 that dissipates lipid to generate heat and defend against obesity. The global epidemic of obesity and its associated metabolic diseases urge an imperative need for understating the regulation of adipogenesis...
October 12, 2016: Journal of Cellular Physiology
Qingzhang Zhu, Sarbani Ghoshal, Ana Rodrigues, Su Gao, Alice Asterian, Theodore M Kamenecka, James C Barrow, Anutosh Chakraborty
Enhancing energy expenditure (EE) is an attractive strategy to combat obesity and diabetes. Global deletion of Ip6k1 protects mice from diet-induced obesity (DIO) and insulin resistance, but the tissue-specific mechanism by which IP6K1 regulates body weight is unknown. Here, we have demonstrated that IP6K1 regulates fat accumulation by modulating AMPK-mediated adipocyte energy metabolism. Cold exposure led to downregulation of Ip6k1 in murine inguinal and retroperitoneal white adipose tissue (IWAT and RWAT) depots...
October 4, 2016: Journal of Clinical Investigation
Antonia Sassmann-Schweda, Pratibha Singh, Cong Tang, Astrid Wietelmann, Nina Wettschureck, Stefan Offermanns
Obesity is an increasing health problem worldwide, and nonsurgical strategies to treat obesity have remained rather inefficient. We here show that acute loss of TGF-β-activated kinase 1 (TAK1) in adipocytes results in an increased rate of apoptotic adipocyte death and increased numbers of M2 macrophages in white adipose tissue. Mice with adipocyte-specific TAK1 deficiency have reduced adipocyte numbers and are resistant to obesity induced by a high-fat diet or leptin deficiency. In addition, adipocyte-specific TAK1-deficient mice under a high-fat diet showed increased energy expenditure, which was accompanied by enhanced expression of the uncoupling protein UCP1...
May 19, 2016: JCI Insight
J Brenmoehl, D Ohde, E Albrecht, C Walz, A Tuchscherer, A Hoeflich
For the assessment of genetic or conditional factors of fat cell browning, novel and polygenic animal models are required. Therefore, the long-term selected polygenic mouse line DUhTP originally established in Dummerstorf for high treadmill performance is used. DUhTP mice are characterized by increased fat accumulation in the sedentary condition and elevated fat mobilization during mild voluntary physical activity. In the present study, the phenotype of fat cell browning of subcutaneous fat and a potential effect on oral glucose tolerance, an indicator of metabolic health, were addressed in DUhTP mice...
September 30, 2016: Journal of Comparative Physiology. B, Biochemical, Systemic, and Environmental Physiology
Anji Lian, Xin Li, Quan Jiang
Irisin, the product of fibronectin type III domain-containing protein 5 (FNDC5) gene, is well-documented to be a regulator of energy metabolism. At present, not much is known about its biological function in non-mammalian species. In this study, a full-length tilapia FDNC5 was cloned and its tissue expression pattern has been confirmed. Based on the sequence obtained, we produced and purified recombinant irisin which could induce uncoupling protein 1 (UCP1) gene expression in tilapia hepatocytes. Further, the rabbit polyclonal irisin antiserum was produced and its specificity was confirmed by antiserum preabsorption...
September 30, 2016: Molecular and Cellular Endocrinology
Sílvia Rocha-Rodrigues, Amaia Rodríguez, Alexandra M Gouveia, Inês O Gonçalves, Sara Becerril, Beatriz Ramírez, Jorge Beleza, Gema Frühbeck, António Ascensão, José Magalhães
AIMS: Exercise-stimulated myokine secretion into circulation may be related with browning in white adipose tissue (WAT), representing a positive metabolic effect on whole-body fat mass. However, limited information is yet available regarding the impact of exercise on myokine-related modulation of adipocyte phenotype in WAT from obese rats. MAIN METHODS: Sprague-Dawley rats (n=60) were divided into sedentary and voluntary physical activity (VPA) groups and fed with standard (35kcal% fat) or high-fat (HFD, 71kcal% fat)-isoenergetic diets...
September 27, 2016: Life Sciences
Francesc Villarroya, Marion Peyrou, Marta Giralt
Regulated transcription of the uncoupling protein-1 (UCP1) gene, and subsequent UCP1 protein synthesis, is a hallmark of the acquisition of the differentiated, thermogenically competent status of brown and beige/brite adipocytes, as well as of the responsiveness of brown and beige/brite adipocytes to adaptive regulation of thermogenic activity. The 5' non-coding region of the UCP1 gene contains regulatory elements that confer tissue specificity, differentiation dependence, and neuro-hormonal regulation to UCP1 gene transcription...
October 5, 2016: Biochimie
Huitong Zhou, Long Cheng, Seung Ok Byun, Wumaierjiang Aizimu, Miriam C Hodge, Grant R Edwards, Jon Gh Hickford
Uncoupling protein-1 (UCP1) plays a role in the regulation of body temperature, metabolic rate and energy expenditure in animals. While variation in UCP1 and its phenotypic effect has been investigated in humans and sheep, little is known about this gene in cattle. In this study, four regions of bovine UCP1 were investigated in 612 Holstein-Friesian × Jersey (HF × J) dairy cows using polymerase chain reaction-single stranded conformational polymorphism (PCR-SSCP) analyses. In the four regions of the gene analysed, a total of 13 SNPs were detected...
October 3, 2016: Journal of Dairy Research
Xingwei Liang, Qiyuan Yang, Lupei Zhang, Joseph W Maricelli, Buel D Rodgers, Mei-Jun Zhu, Min Du
Maternal obesity and high-fat diet (HFD) predisposes offspring to obesity and metabolic diseases. Due to uncoupling, brown adipose tissue (BAT) dissipates energy via heat generation, mitigating obesity and diabetes. The lactation stage is a manageable period for improving the health of offspring of obese mothers, but the impact of maternal HFD during lactation on offspring BAT function is unknown. To determine, female mice were fed either a control or HFD during lactation. At weaning, HFD offspring gained more body weight and had greater body fat mass compared to the control, and these differences maintained into adulthood, which correlated with glucose intolerance and insulin resistance in HFD offspring...
September 30, 2016: Scientific Reports
Annabel Y Minard, Shi-Xiong Tan, Pengyi Yang, Daniel J Fazakerley, Westa Domanova, Benjamin L Parker, Sean J Humphrey, Raja Jothi, Jacqueline Stöckli, David E James
FGF21 improves the metabolic profile of obese animals through its actions on adipocytes. To elucidate the signaling network responsible for mediating these effects, we quantified dynamic changes in the adipocyte phosphoproteome following acute exposure to FGF21. FGF21 regulated a network of 821 phosphosites on 542 proteins. A major FGF21-regulated signaling node was mTORC1/S6K. In contrast to insulin, FGF21 activated mTORC1 via MAPK rather than through the canonical PI3K/AKT pathway. Activation of mTORC1/S6K by FGF21 was surprising because this is thought to contribute to deleterious metabolic effects such as obesity and insulin resistance...
September 27, 2016: Cell Reports
Sadat A Aziz, Luisa A Wakeling, Satomi Miwa, Goiuri Alberdi, John E Hesketh, Dianne Ford
Promoting the development of brown or beige adipose tissue may protect against obesity and related metabolic features, and potentially underlies protective effects of genistein in mice. We observed that application of genistein to 3T3-L1 adipocytes changed the lipid distribution from large droplets to a multilocular distribution, reduced mRNAs indicative of white adipocytes (ACC, Fasn, Fabp4, HSL, chemerin and resistin) and increased mRNAs that are a characteristic feature of brown/beige adipocytes (CD-137 and UCP1)...
September 27, 2016: Molecular Nutrition & Food Research
Christopher L Riley, Christine Dao, M Alexander Kenaston, Luigina Muto, Shohei Kohno, Sara M Nowinski, Ashley D Solmonson, Matthew Pfeiffer, Michael N Sack, Zhongping Lu, Giuseppe Fiermonte, Jon E Sprague, Edward M Mills
Uncoupling protein 1 (UCP1) is the established mediator of brown adipose tissue dependent thermogenesis. In contrast, the role of UCP3, expressed in both skeletal muscle and BAT, in thermoregulatory physiology is less well understood. Here, we show that mice lacking UCP3 (UCP3KO) have impaired sympathomimetic (methamphetamine) and completely abrogated lipopolysaccharide (LPS) thermogenesis, but a normal response to norepinephrine. By comparison, UCP1 knockout (UCP1KO) mice exhibit blunted methamphetamine and fully inhibited norepinephrine thermogenesis, but an increased febrile response to LPS...
September 20, 2016: Journal of Physiology
Yuanting Cui, Li Li, Peng Gao, Liqun Ma, Daoyan Liu, Zhiming Zhu
OBJECTIVE: Obesity is global healthy problem. Uncoupling protein 1 (UCP1) mainly expresses on brown adipose tissue (BAT), uncouples energy substrate oxidation from mitochondrial ATP production and results in the loss of potential energy as heat. Transient receptor potential vanilloid subfamily, member 1 (TRPV1) is the heat-gated cation ion channel. The aim of this study was to investigate the in vivo role of TRPV1 and UCP1 co-action in obesity. DESIGN AND METHOD: We generated and characterized UCP1 mice lacking TRPV1 activity (TRPV1/UCP1 mice)...
September 2016: Journal of Hypertension
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