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https://www.readbyqxmd.com/read/28886439/chronic-high-sucrose-diet-increases-fibroblast-growth-factor-21-production-and-energy-expenditure-in-mice
#1
Ryuya Maekawa, Yusuke Seino, Hidetada Ogata, Masatoshi Murase, Atsushi Iida, Kaori Hosokawa, Erina Joo, Norio Harada, Shin Tsunekawa, Yoji Hamada, Yutaka Oiso, Nobuya Inagaki, Yoshitaka Hayashi, Hiroshi Arima
Excess carbohydrate intake causes obesity in humans. On the other hand, acute administration of fructose, glucose or sucrose in experimental animals has been shown to increase the plasma concentration of anti-obesity hormones such as glucagon-like peptide 1 (GLP-1) and Fibroblast growth factor 21 (FGF21), which contribute to reducing body weight. However, the secretion and action of GLP-1 and FGF21 in mice chronically fed a high-sucrose diet has not been investigated. To address the role of anti-obesity hormones in response to increased sucrose intake, we analyzed mice fed a high-sucrose diet, a high-starch diet or a normal diet for 15 weeks...
July 25, 2017: Journal of Nutritional Biochemistry
https://www.readbyqxmd.com/read/28846667/klebsazolicin-inhibits-70s-ribosome-by-obstructing-the-peptide-exit-tunnel
#2
Mikhail Metelev, Ilya A Osterman, Dmitry Ghilarov, Nelli F Khabibullina, Alexander Yakimov, Konstantin Shabalin, Irina Utkina, Dmitry Y Travin, Ekaterina S Komarova, Marina Serebryakova, Tatyana Artamonova, Mikhail Khodorkovskii, Andrey L Konevega, Petr V Sergiev, Konstantin Severinov, Yury S Polikanov
Whereas screening of the small-molecule metabolites produced by most cultivatable microorganisms often results in the rediscovery of known compounds, genome-mining programs allow researchers to harness much greater chemical diversity, and result in the discovery of new molecular scaffolds. Here we report the genome-guided identification of a new antibiotic, klebsazolicin (KLB), from Klebsiella pneumoniae that inhibits the growth of sensitive cells by targeting ribosomes. A ribosomally synthesized post-translationally modified peptide (RiPP), KLB is characterized by the presence of a unique N-terminal amidine ring that is essential for its activity...
October 2017: Nature Chemical Biology
https://www.readbyqxmd.com/read/28754744/klb-encoding-%C3%AE-klotho-is-mutated-in-patients-with-congenital-hypogonadotropic-hypogonadism
#3
Cheng Xu, Andrea Messina, Emmanuel Somm, Hichem Miraoui, Tarja Kinnunen, James Acierno, Nicolas J Niederländer, Justine Bouilly, Andrew A Dwyer, Yisrael Sidis, Daniele Cassatella, Gerasimos P Sykiotis, Richard Quinton, Christian De Geyter, Mirjam Dirlewanger, Valérie Schwitzgebel, Trevor R Cole, Andrew A Toogood, Jeremy Mw Kirk, Lacey Plummer, Urs Albrecht, William F Crowley, Moosa Mohammadi, Manuel Tena-Sempere, Vincent Prevot, Nelly Pitteloud
Congenital hypogonadotropic hypogonadism (CHH) is a rare genetic form of isolated gonadotropin-releasing hormone (GnRH) deficiency caused by mutations in > 30 genes. Fibroblast growth factor receptor 1 (FGFR1) is the most frequently mutated gene in CHH and is implicated in GnRH neuron development and maintenance. We note that a CHH FGFR1 mutation (p.L342S) decreases signaling of the metabolic regulator FGF21 by impairing the association of FGFR1 with β-Klotho (KLB), the obligate co-receptor for FGF21. We thus hypothesized that the metabolic FGF21/KLB/FGFR1 pathway is involved in CHH Genetic screening of 334 CHH patients identified seven heterozygous loss-of-function KLB mutations in 13 patients (4%)...
July 28, 2017: EMBO Molecular Medicine
https://www.readbyqxmd.com/read/28721439/effects-of-insulin-and-exercise-training-on-fgf21-its-receptors-and-target-genes-in-obesity-and-type-2-diabetes
#4
Rikke Kruse, Sara G Vienberg, Birgitte F Vind, Birgitte Andersen, Kurt Højlund
AIMS/HYPOTHESIS: Pharmacological doses of FGF21 improve glucose tolerance, lipid metabolism and energy expenditure in rodents. Induced expression and secretion of FGF21 from muscle may increase browning of white adipose tissue (WAT) in a myokine-like manner. Recent studies have reported that insulin and exercise increase FGF21 in plasma. Obesity and type 2 diabetes are potentially FGF21-resistant states, but to what extent FGF21 responses to insulin and exercise training are preserved, and whether FGF21, its receptors and target genes are altered, remains to be established...
July 18, 2017: Diabetologia
https://www.readbyqxmd.com/read/28650457/fibroblast-growth-factor-19-regulates-skeletal-muscle-mass-and-ameliorates-muscle-wasting-in-mice
#5
Bérengère Benoit, Emmanuelle Meugnier, Martina Castelli, Stéphanie Chanon, Aurélie Vieille-Marchiset, Christine Durand, Nadia Bendridi, Sandra Pesenti, Pierre-Axel Monternier, Anne-Cécile Durieux, Damien Freyssenet, Jennifer Rieusset, Etienne Lefai, Hubert Vidal, Jérôme Ruzzin
The endocrine-derived hormone fibroblast growth factor (FGF) 19 has recently emerged as a potential target for treating metabolic disease. Given that skeletal muscle is a key metabolic organ, we explored the role of FGF19 in that tissue. Here we report a novel function of FGF19 in regulating skeletal muscle mass through enlargement of muscle fiber size, and in protecting muscle from atrophy. Treatment with FGF19 causes skeletal muscle hypertrophy in mice, while physiological and pharmacological doses of FGF19 substantially increase the size of human myotubes in vitro...
August 2017: Nature Medicine
https://www.readbyqxmd.com/read/28552744/reduction-in-serum-fibroblast-growth-factor-21-after-gastric-bypass-is-related-to-changes-in-hepatic-fat-content
#6
Karen Fjeldborg, Steen B Pedersen, Holger J Møller, Bjørn Richelsen
BACKGROUND: Fibroblast growth factor 21 (FGF21) is elevated in obesity. OBJECTIVES: We investigated the circulating level of FGF21 and the expression of FGF21, beta-klotho (KLB), and FGF receptor 1 (FGFR1) in adipose tissue in relation to weight, fat distribution, and Roux-en-Y gastric bypass (RYGB)-induced weight loss. SETTING: The Department of Endocrinology at Aarhus University Hospital. METHODS: Thirty-one obese patients were enrolled...
April 7, 2017: Surgery for Obesity and related Diseases: Official Journal of the American Society for Bariatric Surgery
https://www.readbyqxmd.com/read/28525362/fgf21-receptor-agonists-an-emerging-therapeutic-class-for-obesity-related-diseases
#7
REVIEW
Junichiro Sonoda, Mark Z Chen, Amos Baruch
Fibroblast growth factor 21 (FGF21) analogs and FGF21 receptor agonists (FGF21RAs) that mimic FGF21 ligand activity constitute the new "FGF21-class" of anti-obesity and anti-diabetic molecules that improve insulin sensitivity, ameliorate hepatosteatosis and promote weight loss. The metabolic actions of FGF21-class proteins in obese mice are attributed to stimulation of brown fat thermogenesis and increased secretion of adiponectin. The therapeutic utility of this class of molecules is being actively investigated in clinical trials for the treatment of type 2 diabetes and non-alcoholic steatohepatitis (NASH)...
May 19, 2017: Hormone Molecular Biology and Clinical Investigation
https://www.readbyqxmd.com/read/28485404/genetic-contributors-to-variation-in-alcohol-consumption-vary-by-race-ethnicity-in-a-large-multi-ethnic-genome-wide-association-study
#8
E Jorgenson, K K Thai, T J Hoffmann, L C Sakoda, M N Kvale, Y Banda, C Schaefer, N Risch, J Mertens, C Weisner, H Choquet
Alcohol consumption is a complex trait determined by both genetic and environmental factors, and is correlated with the risk of alcohol use disorders. Although a small number of genetic loci have been reported to be associated with variation in alcohol consumption, genetic factors are estimated to explain about half of the variance in alcohol consumption, suggesting that additional loci remain to be discovered. We conducted a genome-wide association study (GWAS) of alcohol consumption in the large Genetic Epidemiology Research in Adult Health and Aging (GERA) cohort, in four race/ethnicity groups: non-Hispanic whites, Hispanic/Latinos, East Asians and African Americans...
September 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/28484310/a-dot-hybridization-assay-for-the-diagnosis-of-bacterial-keratitis
#9
Po-Chiung Fang, Chun-Chih Chien, Hun-Ju Yu, Ren-Wen Ho, Shin-Ling Tseng, Yu-Hsuan Lai, Ming-Tse Kuo
PURPOSE: To evaluate a bacterial dot hybridization (BDH) assay for the diagnosis of bacterial keratitis (BK). METHODS: Sixty-one qualified corneal scrapings from 61 patients with suspected microbial keratitis were collected consecutively and prospectively. Among the 61 patients, 16 cases were BK and 45 cases were non-BK, including fungal keratitis, viral keratitis, parasitic keratitis, and non-microbial keratitis. Molecular diagnosis of BK in these corneal scrapes was performed using the BDH assay with three universal bacterial probes (PB1, PB2, and PB3) and three genus-specific probes (Aci, Klb, and Psu) to detect Acinetobacter, Klebsiella, and Pseudomonas, respectively...
2017: Molecular Vision
https://www.readbyqxmd.com/read/28445152/multiplexed-gene-expression-profiling-identifies-the-fgfr4-pathway-as-a-novel-biomarker-in-intrahepatic-cholangiocarcinoma
#10
Changhoon Yoo, Jihoon Kang, Deokhoon Kim, Kyu-Pyo Kim, Baek-Yeol Ryoo, Seung-Mo Hong, Jung Jin Hwang, Seong-Yun Jeong, Shin Hwang, Ki-Hun Kim, Young-Joo Lee, Klaus P Hoeflich, Oleg Schmidt-Kittler, Stephen Miller, Eun Kyung Choi
BACKGROUND: The fibroblast growth factor receptor 4 (FGFR4) pathway is an essential regulatory component of bile acid synthesis, and its relationship with hepatocellular carcinoma (HCC) has been reported. We investigated the gene expression and clinical significance of FGFR4 and related pathways in intrahepatic cholangiocarcinoma (iCCA). RESULTS: The median age was 56 years (range 30-78) and 34 patients (74%) were male. Six patients (13%) had hepatitis B virus infection, with or without liver cirrhosis...
June 13, 2017: Oncotarget
https://www.readbyqxmd.com/read/28422755/%C3%AE-klotho-deficiency-protects-against-obesity-through-a-crosstalk-between-liver-microbiota-and-brown-adipose-tissue
#11
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/28384532/circadian-patterns-of-xylem-sap-properties-and-their-covariation-with-plant-hydraulic-traits-in-hybrid-aspen
#12
Annika Meitern, Eele Õunapuu-Pikas, Arne Sellin
Physiological processes taking place in plants are subject to diverse circadian patterns but some of them are poorly documented in natural conditions. The daily dynamics of physico-chemical properties of xylem sap and their covariation with tree hydraulic traits were investigated in hybrid aspen (Populus tremula L.×P. tremuloides Michx) in field conditions in order to clarify which environmental drivers govern the daily variation in these parameters. K(+) concentration ([K(+)]), electrical conductivity (σsap), osmolality (Osm) and pH of the xylem sap, as well as branch hydraulic traits, were measured in the field over 24-h cycles...
March 22, 2017: Journal of Plant Physiology
https://www.readbyqxmd.com/read/28249259/fibroblast-growth-factor-15-19-in-hepatocarcinogenesis
#13
REVIEW
Gloria Alvarez-Sola, Iker Uriarte, M Ujue Latasa, Raquel Urtasun, Marina Bárcena-Varela, Maria Elizalde, Maddalen Jiménez, Carlos M Rodriguez-Ortigosa, Fernando J Corrales, Maite G Fernández-Barrena, Carmen Berasain, Matías A Avila
BACKGROUND: Advanced hepatocellular carcinoma (HCC) is a neoplastic disease with a very bad prognosis and increasing worldwide incidence. HCCs are resistant to conventional chemotherapy and the multikinase inhibitor sorafenib is the only agent that has shown some clinical efficacy. It is therefore important to identify key molecular mechanisms driving hepatocarcinogenesis for the development of more efficacious therapies. However, HCCs are heterogeneous tumors and different molecular subclasses have been characterized...
2017: Digestive Diseases
https://www.readbyqxmd.com/read/27911795/klb-is-associated-with-alcohol-drinking-and-its-gene-product-%C3%AE-klotho-is-necessary-for-fgf21-regulation-of-alcohol-preference
#14
Gunter Schumann, Chunyu Liu, Paul O'Reilly, He Gao, Parkyong Song, Bing Xu, Barbara Ruggeri, Najaf Amin, Tianye Jia, Sarah Preis, Marcelo Segura Lepe, Shizuo Akira, Caterina Barbieri, Sebastian Baumeister, Stephane Cauchi, Toni-Kim Clarke, Stefan Enroth, Krista Fischer, Jenni Hällfors, Sarah E Harris, Saskia Hieber, Edith Hofer, Jouke-Jan Hottenga, Åsa Johansson, Peter K Joshi, Niina Kaartinen, Jaana Laitinen, Rozenn Lemaitre, Anu Loukola, Jian'an Luan, Leo-Pekka Lyytikäinen, Massimo Mangino, Ani Manichaikul, Hamdi Mbarek, Yuri Milaneschi, Alireza Moayyeri, Kenneth Mukamal, Christopher Nelson, Jennifer Nettleton, Eemil Partinen, Rajesh Rawal, Antonietta Robino, Lynda Rose, Cinzia Sala, Takashi Satoh, Reinhold Schmidt, Katharina Schraut, Robert Scott, Albert Vernon Smith, John M Starr, Alexander Teumer, Stella Trompet, André G Uitterlinden, Cristina Venturini, Anne-Claire Vergnaud, Niek Verweij, Veronique Vitart, Dragana Vuckovic, Juho Wedenoja, Loic Yengo, Bing Yu, Weihua Zhang, Jing Hua Zhao, Dorret I Boomsma, John Chambers, Daniel I Chasman, Toniolo Daniela, Eco de Geus, Ian Deary, Johan G Eriksson, Tõnu Esko, Volker Eulenburg, Oscar H Franco, Philippe Froguel, Christian Gieger, Hans J Grabe, Vilmundur Gudnason, Ulf Gyllensten, Tamara B Harris, Anna-Liisa Hartikainen, Andrew C Heath, Lynne Hocking, Albert Hofman, Cornelia Huth, Marjo-Riitta Jarvelin, J Wouter Jukema, Jaakko Kaprio, Jaspal S Kooner, Zoltan Kutalik, Jari Lahti, Claudia Langenberg, Terho Lehtimäki, Yongmei Liu, Pamela A F Madden, Nicholas Martin, Alanna Morrison, Brenda Penninx, Nicola Pirastu, Bruce Psaty, Olli Raitakari, Paul Ridker, Richard Rose, Jerome I Rotter, Nilesh J Samani, Helena Schmidt, Tim D Spector, David Stott, David Strachan, Ioanna Tzoulaki, Pim van der Harst, Cornelia M van Duijn, Pedro Marques-Vidal, Peter Vollenweider, Nicholas J Wareham, John B Whitfield, James Wilson, Bruce Wolffenbuttel, Georgy Bakalkin, Evangelos Evangelou, Yun Liu, Kenneth M Rice, Sylvane Desrivières, Steven A Kliewer, David J Mangelsdorf, Christian P Müller, Daniel Levy, Paul Elliott
Excessive alcohol consumption is a major public health problem worldwide. Although drinking habits are known to be inherited, few genes have been identified that are robustly linked to alcohol drinking. We conducted a genome-wide association metaanalysis and replication study among >105,000 individuals of European ancestry and identified β-Klotho (KLB) as a locus associated with alcohol consumption (rs11940694; P = 9.2 × 10(-12)). β-Klotho is an obligate coreceptor for the hormone FGF21, which is secreted from the liver and implicated in macronutrient preference in humans...
December 13, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27878865/fibroblast-growth-factor-21-night-watch-advances-and-uncertainties-in-the-field
#15
REVIEW
A Kharitonenkov, R DiMarchi
Fibroblast growth factor (FGF) 21 belongs to a hormone-like subgroup within the FGF superfamily. The members of this subfamily, FGF19, FGF21 and FGF23, are characterized by their reduced binding affinity for heparin that enables them to be transported in the circulation and function in an endocrine manner. It is likely that FGF21 also acts in an autocrine and paracrine fashion, as multiple organs can produce this protein and its plasma concentration seems to be below the level necessary to induce a pharmacological effect...
March 2017: Journal of Internal Medicine
https://www.readbyqxmd.com/read/27717820/discovery-of-an-artificial-peptide-agonist-to-the-fibroblast-growth-factor-receptor-1c-%C3%AE-klotho-complex-from-random-peptide-t7-phage-display
#16
Kotaro Sakamoto, Yayoi Kawata, Yasushi Masuda, Tadashi Umemoto, Takashi Ito, Taiji Asami, Shiro Takekawa, Tetsuya Ohtaki, Hiroshi Inooka
Fibroblast growth factor receptor-1c (FGFR1c)/βKlotho (KLB) complex is a receptor of fibroblast growth factor 21 (FGF21). Pharmacologically, FGF21 shows anti-obesity and anti-diabetic effects upon peripheral administration. Here, we report the development of an artificial peptide agonist to the FGFR1c/KLB heterodimer complex. The peptide, F91-8A07 (LPGRTCREYPDLWWVRCY), was discovered from random peptide T7 phage display and selectively bound to the FGFR1c/KLB complex, but not to FGFR1c and KLB individually...
November 4, 2016: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/27585733/fibroblast-growth-factor-21-fibroblast-growth-factor-receptor-1-and-%C3%AE-klotho-expression-in-bovine-growth-hormone-transgenic-and-growth-hormone-receptor-knockout-mice
#17
Nicole E Brooks, Rikke Hjortebjerg, Brooke E Henry, Edward O List, John J Kopchick, Darlene E Berryman
OBJECTIVE: Although growth hormone (GH) and fibroblast growth factor 21 (FGF21) have a reported relationship, FGF21 and its receptor, fibroblast growth factor receptor 1 (FGFR1) and cofactor β-Klotho (KLB), have not been analyzed in chronic states of altered GH action. The objective of this study was to quantify circulating FGF21 and tissue specific expression of Fgf21, Fgfr1, and Klb in mice with modified GH action. Based on previous studies, we hypothesized that bovine GH transgenic (bGH) mice will be FGF21 resistant and GH receptor knockout (GHR-/-) mice will have normal FGF21 action...
October 2016: Growth Hormone & IGF Research
https://www.readbyqxmd.com/read/27583468/nutritional-regulation-of-fibroblast-growth-factor-21-from-macronutrients-to-bioactive-dietary-compounds
#18
REVIEW
Albert Pérez-Martí, Viviana Sandoval, Pedro F Marrero, Diego Haro, Joana Relat
Obesity is a worldwide health problem mainly due to its associated comorbidities. Fibroblast growth factor 21 (FGF21) is a peptide hormone involved in metabolic homeostasis in healthy individuals and considered a promising therapeutic candidate for the treatment of obesity. FGF21 is predominantly produced by the liver but also by other tissues, such as white adipose tissue (WAT), brown adipose tissue (BAT), skeletal muscle, and pancreas in response to different stimuli such as cold and different nutritional challenges that include fasting, high-fat diets (HFDs), ketogenic diets, some amino acid-deficient diets, low protein diets, high carbohydrate diets or specific dietary bioactive compounds...
September 1, 2016: Hormone Molecular Biology and Clinical Investigation
https://www.readbyqxmd.com/read/27497200/experimental-computational-and-chemometrics-studies-of-bsa-vitamin-b6-interaction-by-uv-vis-ft-ir-fluorescence-spectroscopy-molecular-dynamics-simulation-and-hard-soft-modeling-methods
#19
Firouzeh Manouchehri, Yahya Izadmanesh, Elham Aghaee, Jahan B Ghasemi
The interaction of pyridoxine (Vitamin B6) with bovine serum albumin (BSA) is investigated under pseudo-physiological conditions by UV-Vis, fluorescence and FTIR spectroscopy. The intrinsic fluorescence of BSA was quenched by VB6, which was rationalized in terms of the static quenching mechanism. According to fluorescence quenching calculations, the bimolecular quenching constant (kq), dynamic quenching (KSV) and static quenching (KLB) at 310K were obtained. The efficiency of energy transfer and the distance between the donor (BSA) and the acceptor (VB6) were calculated by Foster's non-radiative energy transfer theory and were equal to 41...
October 2016: Bioorganic Chemistry
https://www.readbyqxmd.com/read/27470139/fibroblast-growth-factor-21-reflects-liver-fat-accumulation-and-dysregulation-of-signalling-pathways-in-the-liver-of-c57bl-6j-mice
#20
Fenni Rusli, Joris Deelen, Evi Andriyani, Mark V Boekschoten, Carolien Lute, Erik B van den Akker, Michael Müller, Marian Beekman, Wilma T Steegenga
Fibroblast growth factor 21 (Fgf21) has emerged as a potential plasma marker to diagnose non-alcoholic fatty liver disease (NAFLD). To study the molecular processes underlying the association of plasma Fgf21 with NAFLD, we explored the liver transcriptome data of a mild NAFLD model of aging C57BL/6J mice at 12, 24, and 28 months of age. The plasma Fgf21 level significantly correlated with intrahepatic triglyceride content. At the molecular level, elevated plasma Fgf21 levels were associated with dysregulated metabolic and cancer-related pathways...
2016: Scientific Reports
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