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https://www.readbyqxmd.com/read/28549912/fatty-liver-and-fgf21-physiology
#1
REVIEW
Eleftheria Maratos-Flier
Non alcoholic fatty liver disease is linked to obesity and the metabolic syndrome. As rates of obesity rise it has become the major etiology of liver dysfunction. Despite intense study the molecular mechanisms contributing to the onset of fatty liver remain debatable. Furthermore, few therapies exist and as a result dietary therapy is commonly prescribed and remains problematic. Fibroblast growth factor is a complex metabolic regulator that is synthesized in multiple organs including the liver, with resulting complex systemic effects...
May 23, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/28537053/fibroblast-growth-factor-21-mimetics-for-treating-atherosclerosis
#2
REVIEW
Kelvin H M Kwok, Karen S L Lam
Fibroblast growth factor 21 (FGF21) is an atypical member of the FGF family. Acting in an endocrine fashion, it increases glucose uptake, modulates lipid metabolism, and sensitizes insulin response in metabolically active organs, including the liver and adipose tissue. Emerging evidence shows a strong correlation between circulating FGF21 levels and the incidence and severity of atherosclerosis. Animal studies have demonstrated a beneficial role of FGF21 in protecting against aberrant lipid profile, while recent development in FGF21 mimetics has provided further insight into the lipid-lowering effects of FGF21 signaling...
May 19, 2017: Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28525362/fgf21-receptor-agonists-an-emerging-therapeutic-class-for-obesity-related-diseases
#3
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/28521869/high-fgf21-levels-are-associated-with-altered-bone-homeostasis-in-hiv-1-infected-patients
#4
José M Gallego-Escuredo, Maria Karuna Lamarca, Joan Villarroya, Joan C Domingo, Ma Gracia Mateo, Ma Del Mar Gutierrez, Francesc Vidal, Francesc Villarroya, Pere Domingo, Marta Giralt
BACKGROUND: Fibroblast growth factor-21 (FGF21) has emerged as an important regulator of glucose, lipid, and body weight homeostasis. However, recent experimental studies have reported that increased FGF21 levels may lead to bone loss. OBJECTIVE: To assess the relationship of serum FGF21 levels and altered bone homeostasis in HIV-1-infected patients. DESIGN: Cross-sectional study of 137 HIV-1-infected patients and 35 healthy controls conducted at the Hospital de la Santa Creu i Sant Pau, Barcelona...
June 2017: Metabolism: Clinical and Experimental
https://www.readbyqxmd.com/read/28520765/an-integrative-analysis-of-tissue-specific-transcriptomic-and-metabolomic-responses-to-short-term-dietary-methionine-restriction-in-mice
#5
Sujoy Ghosh, Laura A Forney, Desiree Wanders, Kirsten P Stone, Thomas W Gettys
Dietary methionine restriction (MR) produces a coordinated series of transcriptional responses in peripheral tissues that limit fat accretion, remodel lipid metabolism in liver and adipose tissue, and improve overall insulin sensitivity. Hepatic sensing of reduced methionine leads to induction and release of fibroblast growth factor 21 (FGF21), which acts centrally to increase sympathetic tone and activate thermogenesis in adipose tissue. FGF21 also has direct effects in adipose to enhance glucose uptake and oxidation...
2017: PloS One
https://www.readbyqxmd.com/read/28515909/metabolic-role-of-fibroblast-growth-factor-21-in-liver-adipose-and-nervous-system-tissues
#6
Xiaolong Lin, Yuan Bo Liu, Huijun Hu
The hepatokine fibroblast growth factor 21 (FGF21) is a novel polypeptide ligand, which is involved in glucose and lipid metabolism, and contributes significantly to lowering body weight and enhancing insulin sensitivity. A large number of pre-clinical and clinical results demonstrate that FGF21 is a potential drug target for treating obesity and type 2 diabetes mellitus. In the present review, the tissue specific actions and molecular mechanisms of FGF21 are discussed with a focus on the liver, adipose tissue and nervous system, as well as investigating the outcomes of clinical trials of FGF21, with the aim of interpreting and delineating the complexity physiology of FGF21...
May 2017: Biomedical Reports
https://www.readbyqxmd.com/read/28498888/cardiomyocyte-specific-loss-of-mitochondrial-p32-c1qbp-causes-cardiomyopathy-and-activates-stress-responses
#7
Toshiro Saito, Takeshi Uchiumi, Mikako Yagi, Rie Amamoto, Daiki Setoyama, Yuichi Matsushima, Dongchon Kang
Aims: Mitochondria are important organelles, dedicated to energy production. Mitochondrial p32/C1qbp, which functions as an RNA and protein chaperone, interacts with mitochondrial mRNA and is indispensable for mitochondrial function through its regulation of mitochondrial translation in cultured cell lines. However, the precise role of p32/C1qbp in vivo is poorly understood because of embryonic lethality in the systemic p32-deficient mouse. The goal of this study was to examine the physiological function of mitochondrial p32/C1qbp in the heart...
May 11, 2017: Cardiovascular Research
https://www.readbyqxmd.com/read/28497814/liver-fgf21-the-cause-of-having-a-sweet-tooth
#8
Claire Greenhill
No abstract text is available yet for this article.
May 12, 2017: Nature Reviews. Endocrinology
https://www.readbyqxmd.com/read/28497003/achondroplasia-and-biliary-atresia-a-rare-association-and-review-of-literature
#9
Ranjit I Kylat
Achondroplasia (ACH) occurs in most cases as de novo mutations of the gene-encoding fibroblast growth factor receptor 3 (FGFR3). Biliary atresia (BA) is a progressive neonatal inflammatory and fibro-obliterative cholangiopathy affecting the extra- and intrahepatic biliary tree to varying degrees, and it results in obstruction to bile flow and cholestatic jaundice in neonates. BA is thought to be a multifactorial disease, genome association studies have shown abnormalities in susceptibility genes, and levels of fibroblast growth factor 21 (FGF21) and fibroblast growth factor 23 (FGF23) have been noted to be increased...
June 2017: Journal of Pediatric Genetics
https://www.readbyqxmd.com/read/28494871/mirna-32-drives-brown-fat-thermogenesis-and-trans-activates-subcutaneous-white-fat-browning-in-mice
#10
Raymond Ng, Nurul Attiqah Hussain, Qiongyi Zhang, Chengwei Chang, Hongyu Li, Yanyun Fu, Lei Cao, Weiping Han, Walter Stunkel, Feng Xu
Brown adipose tissue (BAT) activation and subcutaneous white fat browning are essential components of the thermogenic response to cold stimulus in mammals. microRNAs have been shown to regulate both processes in cis. Here, we identify miR-32 as a BAT-specific super-enhancer-associated miRNA in mice that is selectively expressed in BAT and further upregulated during cold exposure. Inhibiting miR-32 in vivo led to impaired cold tolerance, decreased BAT thermogenesis, and compromised white fat browning as a result of reduced serum FGF21 levels...
May 9, 2017: Cell Reports
https://www.readbyqxmd.com/read/28477305/long-term-obestatin-treatment-of-mice-type-2-diabetes-increases-insulin-sensitivity-and-improves-liver-function
#11
Paweł A Kołodziejski, Ewa Pruszyńska-Oszmałek, Mathias Z Strowski, Krzysztof W Nowak
PURPOSE: Obestatin and ghrelin are peptides encoded by the preproghrelin gene. Obestatin inhibits food intake, in addition to regulation of glucose and lipid metabolism. Here, we test the ability of obestatin at improving metabolic control and liver function in type 2 diabetic animals (type 2 diabetes mellitus). METHODS: The effects of chronic obestatin treatment of mice with experimentally induced type 2 diabetes mellitus on serum levels of glucose and lipids, and insulin sensitivity are characterized...
May 5, 2017: Endocrine
https://www.readbyqxmd.com/read/28473464/alterations-in-3-hydroxyisobutyrate-and-fgf21-metabolism-are-associated-with-protein-ingestion-induced-insulin-resistance
#12
Lydia-Ann L S Harris, Gordon I Smith, Bruce W Patterson, Raja S Ramaswamy, Adewole Okunade, Shannon C Kelly, Lane C Porter, Samuel Klein, Jun Yoshino, Bettina Mittendorfer
Systemic hyperaminoacidemia, induced by either intravenous amino acid infusion or protein ingestion, reduces insulin-stimulated glucose disposal. Studies in mice suggest that the valine metabolite 3-hydroxyisobutyrate (3-HIB), fibroblast growth factor 21 (FGF21), adiponectin, and non-esterified fatty acids (NEFA) may be involved in the amino acid-mediated insulin resistance. We therefore measured the rate of glucose disposal, and plasma 3-HIB, FGF21, adiponectin, and NEFA concentrations in 30 women during basal conditions and during a hyperinsulinemic-euglycemic clamp procedure (HECP) with and without concomitant ingestion of protein (n=15) or an amount of leucine that matched the amount in the protein (n=15)...
May 4, 2017: Diabetes
https://www.readbyqxmd.com/read/28472473/fgf21-is-required-for-cardiac-remodeling-in-pregnancy
#13
I Redondo-Angulo, A Mas-Stachurska, M Sitges, F J Tinahones, M Giralt, F Villarroya, A Planavila
Aims—: Fibroblast growth factor-21 (Fgf21) is an endocrine factor that contributes to many physiological and pathological processes, mainly via its action as a metabolic regulator. Recent studies have shown that Fgf21 plays an important role in cardiac tissue. Pregnancy offers a physiological model of adaptive and reversible heart enlargement, but the molecular mechanisms underlying this cardiac hypertrophy are poorly understood. Therefore, the aim was to analyze the role of Fgf21 during late pregnancy, and assess the physiological relevance of Fgf21 for cardiac tissue during this process...
May 4, 2017: Cardiovascular Research
https://www.readbyqxmd.com/read/28467924/fgf21-is-a-sugar-induced-hormone-associated-with-sweet-intake-and-preference-in-humans
#14
Susanna Søberg, Camilla H Sandholt, Naja Z Jespersen, Ulla Toft, Anja L Madsen, Stephanie von Holstein-Rathlou, Trisha J Grevengoed, Karl B Christensen, Wender L P Bredie, Matthew J Potthoff, Thomas P J Solomon, Camilla Scheele, Allan Linneberg, Torben Jørgensen, Oluf Pedersen, Torben Hansen, Matthew P Gillum, Niels Grarup
The liking and selective ingestion of palatable foods-including sweets-is biologically controlled, and dysfunction of this regulation may promote unhealthy eating, obesity, and disease. The hepatokine fibroblast growth factor 21 (FGF21) reduces sweet consumption in rodents and primates, whereas knockout of Fgf21 increases sugar consumption in mice. To investigate the relevance of these findings in humans, we genotyped variants in the FGF21 locus in participants from the Danish Inter99 cohort (n = 6,514) and examined their relationship with a detailed range of food and ingestive behaviors...
May 2, 2017: Cell Metabolism
https://www.readbyqxmd.com/read/28466020/identification-of-sp1-as-a-transcription-activator-to-regulate-fibroblast-growth-factor-21-gene-expression
#15
Shuqin Chen, Huating Li, Jing Zhang, Shan Jiang, Mingliang Zhang, Yilan Xu, Kun Dong, Ying Yang, Qichen Fang, Weiping Jia
Fibroblast growth factor 21 (FGF21) is a metabolic hormone with multiple beneficial effects on lipid and glucose homeostasis. Previous study demonstrated that FGF21 might be one of the Sp1 target genes. However, the transcriptional role of Sp1 on FGF21 in adipose tissue and liver has not been reported. In this study, we found that the proximal promoter of mouse FGF21 is located between -63 and -20 containing two putative Sp1-binding sites. Sp1 is a mammalian transcription factor involved in the regulation of many genes during physiological and pathological processes...
2017: BioMed Research International
https://www.readbyqxmd.com/read/28457799/dietary-treatment-of-fatty-liver-high-dietary-protein-content-has-an-antisteatotic-and-antiobesogenic-effect-in-mice
#16
Sonia C Garcia Caraballo, Tine M Comhair, Cornelis H C Dejong, Wouter H Lamers, S Eleonore Koehler
Few studies have assessed the effect of changing ratios of dietary macronutrients on fat accumulation in adipose tissue and organs such as the liver in a 3×n(n≥3) factorial design. We investigated the effects of 7 diets from a single manufacturer containing 11-58en% protein (casein), 0-81en% carbohydrates (CHO; sucrose, maltrodextrin-10 and corn starch), and 8-42en% fat (triheptanoin, olive oil or cocoa butter) in C57BL/6J mice, a good model for diet-induced obesity and fatty liver. The diets were fed for 3weeks to wild-type and hyperlipidemic male and female mice...
April 28, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28451950/the-role-and-potential-therapeutic-implications-of-the-fibroblast-growth-factors-in-energy-balance-and-type-2-diabetes
#17
REVIEW
Maitane Izaguirre, María J Gil, Ignacio Monreal, Fabrizio Montecucco, Gema Frühbeck, Victoria Catalán
PURPOSE OF REVIEW: Obesity and its associated metabolic diseases have reached epidemic proportions worldwide, reducing life expectancy and quality of life. Several drugs have been tested to treat these diseases but many of them have damaging side effects. Consequently, there is an urgent need to develop more effective therapies. Recently, endocrine fibroblast growth factors (FGFs) have become attractive targets in the treatment of metabolic diseases. This review summarizes their most important functions as well as FGF-based therapies for the treatment of obesity and type 2 diabetes (T2D)...
June 2017: Current Diabetes Reports
https://www.readbyqxmd.com/read/28447390/high-non-esterified-fatty-acid-concentrations-promote-expression-and-secretion-of-fibroblast-growth-factor-21-in-calf-hepatocytes-cultured-in-vitro
#18
J G Wang, Y Z Guo, Y Z Kong, S Dai, B Y Zhao
Negative energy balance is considered as the pathological basis of energy metabolic disorders in periparturient dairy cows. Serum non-esterified fatty acids (NEFA) are one of the most important indicators of energy balance status. Fibroblast growth factor 21 (FGF21) has been identified as a hepatokine involved in regulation of metabolic adaptations, such as promoting hepatic lipid oxidation and ketogenesis, during energy deprivation. However, the direct effects of NEFA on FGF21 expression and secretion in bovine hepatocytes are not entirely clear...
April 26, 2017: Journal of Animal Physiology and Animal Nutrition
https://www.readbyqxmd.com/read/28445152/multiplexed-gene-expression-profiling-identifies-the-fgfr4-pathway-as-a-novel-biomarker-in-intrahepatic-cholangiocarcinoma
#19
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...
April 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/28437237/proteomics-in-hypothermia-as-adjunctive-therapy-in-patients-with-st-segment-elevation-myocardial-infarction-a-chill-mi-substudy
#20
Moman A Mohammad, Marco Noc, Irene Lang, Michael Holzer, Peter Clemmensen, Ulf Jensen, Bernhard Metzler, David Erlinge
Cardiovascular and inflammatory biomarkers in therapeutic hypothermia have been studied in cardiac arrest, but data on patients with ST-segment elevation myocardial infarction (STEMI) treated with therapeutic hypothermia are currently unavailable. A multiplex proximity extension assay allowed us to measure 157 cardiovascular disease (CVD) and inflammatory disease-related biomarkers in patients from the international, multicenter, and randomized trial; CHILL-myocardial infarction (MI) and to explore the associations of cardiovascular and inflammatory biomarkers...
March 2, 2017: Therapeutic Hypothermia and Temperature Management
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