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Fgf21

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https://www.readbyqxmd.com/read/28199833/fgf21-administration-suppresses-retinal-and-choroidal-neovascularization-in-mice
#1
Zhongjie Fu, Yan Gong, Raffael Liegl, Zhongxiao Wang, Chi-Hsiu Liu, Steven S Meng, Samuel B Burnim, Nicholas J Saba, Thomas W Fredrick, Peyton C Morss, Ann Hellstrom, Saswata Talukdar, Lois E H Smith
Pathological neovascularization, a leading cause of blindness, is seen in retinopathy of prematurity, diabetic retinopathy, and age-related macular degeneration. Using a mouse model of hypoxia-driven retinal neovascularization, we find that fibroblast growth factor 21 (FGF21) administration suppresses, and FGF21 deficiency worsens, retinal neovessel growth. The protective effect of FGF21 against neovessel growth was abolished in adiponectin (APN)-deficient mice. FGF21 administration also decreased neovascular lesions in two models of neovascular age-related macular degeneration: very-low-density lipoprotein-receptor-deficient mice with retinal angiomatous proliferation and laser-induced choroidal neovascularization...
February 14, 2017: Cell Reports
https://www.readbyqxmd.com/read/28199304/adipose-derived-circulating-mirnas-regulate-gene-expression-in-other-tissues
#2
Thomas Thomou, Marcelo A Mori, Jonathan M Dreyfuss, Masahiro Konishi, Masaji Sakaguchi, Christian Wolfrum, Tata Nageswara Rao, Jonathon N Winnay, Ruben Garcia-Martin, Steven K Grinspoon, Phillip Gorden, C Ronald Kahn
Adipose tissue is a major site of energy storage and has a role in the regulation of metabolism through the release of adipokines. Here we show that mice with an adipose-tissue-specific knockout of the microRNA (miRNA)-processing enzyme Dicer (ADicerKO), as well as humans with lipodystrophy, exhibit a substantial decrease in levels of circulating exosomal miRNAs. Transplantation of both white and brown adipose tissue-brown especially-into ADicerKO mice restores the level of numerous circulating miRNAs that are associated with an improvement in glucose tolerance and a reduction in hepatic Fgf21 mRNA and circulating FGF21...
February 15, 2017: Nature
https://www.readbyqxmd.com/read/28191538/lipodystrophy-hiv-related-and-fgf21-a-new-marker-to-follow-the-progression-of-lipodystrophy
#3
Stefano Benedini, Livio Luzi
Recently new evidence about fibroblast growth factor 21 (FGF21) highlights the opportunities to use this molecule in new pharmaceutical formulations to combat type 2 diabetes and metabolic syndrome. It is well known that HIV is per se a condition of insulin resistance and in particular the patient with HIV-related lipodystrophy has a condition strictly related to metabolic syndrome. Lipodystrophy is associated with severe metabolic side effects, including dyslipidemia, hepatic insulin resistance, and lipid oxidation impairment...
December 1, 2016: Journal of Translational Internal Medicine
https://www.readbyqxmd.com/read/28191311/supplemental-smartamine-m-in-higher-energy-diets-during-the-prepartal-period-improves-hepatic-biomarkers-of-health-and-oxidative-status-in-holstein-cows
#4
Mario Vailati-Riboni, Johan S Osorio, Erminio Trevisi, Daniel Luchini, Juan J Loor
BACKGROUND: Feeding higher-energy prepartum is a common practice in the dairy industry. However, recent data underscore how it could reduce performance, deepen negative energy balance, and augment inflammation and oxidative stress in fresh cows. We tested the effectiveness of rumen-protected methionine in preventing the negative effect of feeding a higher-energy prepartum. Multiparous Holstein cows were fed a control lower-energy diet (CON, 1.24 Mcal/kg DM; high-straw) during the whole dry period (~50 d), or were switched to a higher-energy (OVE, 1...
2017: Journal of Animal Science and Biotechnology
https://www.readbyqxmd.com/read/28188284/glucagon-and-insulin-cooperatively-stimulate-fibroblast-growth-factor-21-gene-transcription-by-increasing-the-expression-of-activating-transcription-factor-4
#5
Kimberly M Alonge, Gordon P Meares, F Bradley Hillgartner
Previous studies have shown that glucagon cooperatively interacts with insulin to stimulate hepatic fibroblast growth factor 21 (FGF21) gene expression. Here, we investigated the mechanism by which glucagon and insulin increased FGF21 gene transcription in primary hepatocyte cultures. Transfection analyses demonstrated that glucagon plus insulin induction of FGF21 transcription was conferred by two activating transcription factor 4 (ATF4) binding sites in the FGF21 gene. Glucagon plus insulin stimulated a 5-fold increase in ATF4 protein abundance, and knockdown of ATF4 expression suppressed the ability of glucagon plus insulin to increase FGF21 expression...
February 10, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28184000/angptl6-expression-is-coupled-with-mitochondrial-oxphos-function-to-regulate-adipose-fgf21
#6
Seul Gi Kang, Hyon-Seung Yi, Min Jeong Choi, Min Jeong Ryu, Saetbyel Jung, Hyo Kyun Chung, Joon Young Chang, Yong Kyung Kim, Seong Eun Lee, Hyeon-Woo Kim, Hoil Choi, Dong Seok Kim, Ju Hee Lee, Koon Soon Kim, Hyun Jin Kim, Chul-Ho Lee, Yuichi Oike, Minho Shong
Recent studies revealed that the inhibition of mitochondrial oxidative phosphorylation (OXPHOS) is coupled with the mitochondrial unfolded protein response, thereby stimulating the secretion of non-cell-autonomous factors, which may control systemic energy metabolism and longevity. However, the nature and roles of non-cell-autonomous factors induced in adipose tissue in response to reduced OXPHOS function remain to be clarified in mammals. CR6-interacting factor 1 (CRIF1) is an essential mitoribosomal protein for the intramitochondrial production of mtDNA-encoded OXPHOS subunits...
February 9, 2017: Journal of Endocrinology
https://www.readbyqxmd.com/read/28181108/circulating-levels-of-fibroblast-growth-factor-21-in-early-stage-diabetic-kidney-disease
#7
A Esteghamati, A Khandan, A Momeni, A Behdadnia, A Ghajar, M S Nikdad, S Noshad, M Nakhjavani, M Afarideh
AIMS/PURPOSE: Fibroblast growth factor 21 (FGF21), a hepatoadipokine with pleiotropic metabolic regulatory actions, is emerging as a novel biomarker of progressive nephropathy. We sought to evaluate circulating FGF21 and its association with clinical and biochemical characteristics as well as the urinary albumin excretion (UAE) rates in a population of patients with type 2 diabetes (T2D) with or without microalbuminuria and their matched healthy controls. METHODS: Cross-sectionally, 130 consecutive individuals comprising patients with T2D with (n = 44) or without (n = 44) microalbuminuria and their healthy controls (n = 42) were recruited for analysis...
February 8, 2017: Irish Journal of Medical Science
https://www.readbyqxmd.com/read/28143735/pharmacological-efficacy-of-fgf21-analogue-liraglutide-and-insulin-glargine-in-treatment-of-type-2-diabetes
#8
Xianlong Ye, Jianying Qi, Dan Yu, Yunzhou Wu, Shenglong Zhu, Shujie Li, Qiang Wu, Guiping Ren, Deshan Li
Fibroblast growth factor 21 (FGF21) is a promising regulator of glucose and lipid metabolism with multiple beneficial effects including hypoglycemic and lipid-lowering. Previous studies have reported that FGF21 is expected to become a new drug for treatment of diabetes. Liraglutide and insulin glargine are the two representative anti-diabetic biological drugs. In the current study, we aim to compare the long-term pharmacological efficacy of mFGF21 (an FGF21 analogue), liraglutide and insulin glargine in type 2 diabetic db/db mice...
January 21, 2017: Journal of Diabetes and its Complications
https://www.readbyqxmd.com/read/28139438/fgf21-deficiency-is-associated-with-childhood-obesity-insulin-resistance-and-hypoadiponectinaemia-the-bcams-study
#9
G Li, J Yin, J Fu, L Li, S F A Grant, C Li, M Li, J Mi, M Li, S Gao
OBJECTIVE: Fibroblast growth factor 21 (FGF21) exerts beneficial effects on metabolic homoeostasis and has been reported to be regulated by adiponectin, leptin and resistin. However, while an association between increased circulating FGF21 and metabolic disorders has been reported in adults, paediatric-specific data are lacking. DESIGN AND METHODS: This study investigated the relationship between FGF21 levels and obesity, insulin resistance (IR), the metabolic syndrome (MetS) and adipokines (adiponectin, leptin and resistin) in a cohort of 3231 Chinese youngsters aged 6-18...
January 27, 2017: Diabetes & Metabolism
https://www.readbyqxmd.com/read/28133364/pancreas-fgf21-gets-the-juices-flowing
#10
David Holmes
No abstract text is available yet for this article.
January 30, 2017: Nature Reviews. Endocrinology
https://www.readbyqxmd.com/read/28131861/alcoholic-fatty-liver-is-enhanced-in-cyp2a5-knockout-mice-the-role-of-the-ppar%C3%AE-fgf21-axis
#11
Xue Chen, Stephen C Ward, Arthur I Cederbaum, Huabao Xiong, Yongke Lu
BACKGROUND & AIMS: Cytochrome P450 2A5 (CYP2A5) is induced by ethanol, and the ethanol induction of CYP2A5 is regulated by nuclear factor-erythroid 2-related factor 2 (NRF2). Cyp2a5 knockout (Cyp2a5(-/-)) mice develop more severe alcoholic fatty liver than Cyp2a5(+/+) mice. Fibroblast growth factor 21 (FGF21), a PPARα-regulated liver hormone, is involved in hepatic lipid metabolism. Alcoholic and non-alcoholic fatty liver are enhanced in Pparα knockout (Pparα(-/-)) mice. This study investigates the relationship between the PPARα-FGF21 axis and the enhanced alcoholic fatty liver in Cyp2a5(-/-) mice...
January 25, 2017: Toxicology
https://www.readbyqxmd.com/read/28131830/suppression-of-nrf2-attenuates-adipogenesis-and-decreases-fgf21-expression-through-ppar-gamma-in-3t3-l1-cells
#12
Bo-Rahm Kim, Gha Young Lee, Hyeree Yu, Hyo Jin Maeng, Tae Jung Oh, Kyoung Min Kim, Jae Hoon Moon, Soo Lim, Hak Chul Jang, Sung Hee Choi
Adipogenesis is the process of differentiation from preadipocytes to adipocytes and is orchestrated by various transcription factors, such as the peroxisome proliferator-activated receptor gamma (PPARγ) and the CCAAT-enhancer-binding protein alpha (C/EBPα). Oxidative stress is also a crucial factor in adipogenesis, and adipocyte differentiation is affected by the cellular redox status. The nuclear factor E2-related factor 2 (Nrf2), which is a basic leucine zipper (bZIP) transcription factor, acts as a regulator of cellular oxidative stress...
January 25, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28129657/physiological-characterization-of-a-novel-ppar-pan-agonist-2-4-5-6-methylenedioxybenzo-d-thiazol-2-yl-2-methylphenoxy-2-methylpropanoic-acid-mhy2013
#13
Hye Jin An, Bonggi Lee, Dae Hyun Kim, Eun Kyeong Lee, Ki Wung Chung, Min Hi Park, Hyoung Oh Jeong, Sung Min Kim, Kyoung Mi Moon, Ye Ra Kim, Seong Jin Kim, Hwi Young Yun, Pusoon Chun, Byung Pal Yu, Hyung Ryong Moon, Hae Young Chung
Recently, agonists targeting multiple peroxisome proliferator-activated receptors (PPARs) have been developed to improve metabolic disorders and minimize the side effects of selective PPAR agonists such as weight gain and dyslipidemia. We newly synthesized six 2-methyl-2-(o-tolyloxy)propanoic acid derivatives based on the structure of a well-known PPAR pan agonist, bezafibrate. Of six compounds, MHY2013 was screened as the strongest activator of three PPAR subtypes based on protein docking simulation and luciferase assays...
25, 2017: Oncotarget
https://www.readbyqxmd.com/read/28123934/circulating-fgf21-in-humans-is-potently-induced-by-short-term-overfeeding-of-carbohydrates
#14
Anne-Marie Lundsgaard, Andreas M Fritzen, Kim A Sjøberg, Lene S Myrmel, Lise Madsen, Jørgen F P Wojtaszewski, Erik A Richter, Bente Kiens
OBJECTIVE: Fibroblast-growth factor 21 (FGF21) is thought to be important in metabolic regulation. Recently, low protein diets have been shown to increase circulating FGF21 levels. However, when energy contribution from dietary protein is lowered, other macronutrients, such as carbohydrates, must be increased to meet eucaloric balance. This raises the possibility that intake of a diet rich in carbohydrates may induce an increase in plasma FGF21 levels per se. Here we studied the role of dietary carbohydrates on the levels of circulating FGF21 and concomitant physiologic effects by feeding healthy men a carbohydrate rich diet without reducing protein intake...
January 2017: Molecular Metabolism
https://www.readbyqxmd.com/read/28123933/a-critical-role-for-chrebp-mediated-fgf21-secretion-in-hepatic-fructose-metabolism
#15
Ffolliott M Fisher, MiSung Kim, Ludivine Doridot, Jeremy C Cunniff, Thomas S Parker, Daniel M Levine, Marc K Hellerstein, Lisa C Hudgins, Eleftheria Maratos-Flier, Mark A Herman
OBJECTIVE: Increased fructose consumption is a contributor to the burgeoning epidemic of non-alcoholic fatty liver disease (NAFLD). Recent evidence indicates that the metabolic hormone FGF21 is regulated by fructose consumption in humans and rodents and may play a functional role in this nutritional context. Here, we sought to define the mechanism by which fructose ingestion regulates FGF21 and determine whether FGF21 contributes to an adaptive metabolic response to fructose consumption...
January 2017: Molecular Metabolism
https://www.readbyqxmd.com/read/28112064/nutrition-infection-and-stunting-the-roles-of-deficiencies-of-individual-nutrients-and-foods-and-of-inflammation-as-determinants-of-reduced-linear-growth-of-children
#16
D Joe Millward
The regulation of linear growth by nutritional and inflammatory influences is examined in terms of growth-plate endochondral ossification, in order to better understand stunted growth in children. Linear growth is controlled by complex genetic, physiological, and nutrient-sensitive endocrine/paracrine/autocrine mediated molecular signalling mechanisms, possibly including sleep adequacy through its influence on growth hormone secretion. Inflammation, which accompanies most infections and environmental enteric dysfunction, inhibits endochondral ossification through the action of mediators including proinflammatory cytokines, the activin A-follistatin system, glucocorticoids and fibroblast growth factor 21 (FGF21)...
January 23, 2017: Nutrition Research Reviews
https://www.readbyqxmd.com/read/28099124/browning-of-white-adipose-tissue-lessons-from-experimental-models
#17
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/28096260/fgf21-mediates-the-thermogenic-and-insulin-sensitizing-effects-of-dietary-methionine-restriction-but-not-its-effects-on-hepatic-lipid-metabolism
#18
Desiree Wanders, Laura A Forney, Kirsten P Stone, David H Burk, Alicia Pierse, Thomas W Gettys
Dietary methionine restriction (MR) produces a rapid and persistent remodeling of white adipose tissue (WAT), increase in energy expenditure (EE), and enhancement of insulin sensitivity. Recent work established that hepatic expression of FGF21 is robustly increased by MR. Based on the known physiological effects of FGF21, Fgf21(-/-) mice were used to test whether FGF21 is an essential mediator of the physiological effects of dietary MR. The MR-induced increase in energy intake and EE, and activation of thermogenesis in WAT and BAT were lost in Fgf21(-/-) mice...
January 17, 2017: Diabetes
https://www.readbyqxmd.com/read/28089565/fgf21-is-an-exocrine-pancreas-secretagogue
#19
Katie C Coate, Genaro Hernandez, Curtis A Thorne, Shengyi Sun, Thao D V Le, Kevin Vale, Steven A Kliewer, David J Mangelsdorf
The metabolic stress hormone FGF21 is highly expressed in exocrine pancreas, where its levels are increased by refeeding and chemically induced pancreatitis. However, its function in the exocrine pancreas remains unknown. Here, we show that FGF21 stimulates digestive enzyme secretion from pancreatic acinar cells through an autocrine/paracrine mechanism that requires signaling through a tyrosine kinase receptor complex composed of an FGF receptor and β-Klotho. Mice lacking FGF21 accumulate zymogen granules and are susceptible to pancreatic ER stress, an effect that is reversed by administration of recombinant FGF21...
February 7, 2017: Cell Metabolism
https://www.readbyqxmd.com/read/28088388/activation-of-gr-but-not-pxr-by-dexamethasone-attenuated-acetaminophen-hepatotoxicities-via-fgf21-induction
#20
Saurabh G Vispute, Pengli Bu, Yuan Le, Xingguo Cheng
Glucocorticoid receptor (GR) signaling is indispensable for cell growth and development, and plays important roles in drug metabolism. Fibroblast growth factor (Fgf) 21, an important regulator of glucose, lipid, and energy metabolism, plays a cytoprotective role by attenuating toxicities induced by chemicals such as dioxins, acetaminophen (APAP), and alcohols. The present study investigates the impact of dexamethasone (DEX)-activated GR on Fgf21 expression and how it affects the progression of APAP-induced hepatotoxicity...
January 11, 2017: Toxicology
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