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Fgf lipid metabolism

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https://www.readbyqxmd.com/read/28088388/activation-of-gr-but-not-pxr-by-dexamethasone-attenuated-acetaminophen-hepatotoxicities-via-fgf21-induction
#1
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
https://www.readbyqxmd.com/read/28041926/chronic-over-expression-of-fibroblast-growth-factor-21-increases-bile-acid-biosynthesis-by-opposing-fgf15-19-action
#2
Jun Zhang, Jamila Gupte, Yan Gong, Jennifer Weiszmann, Yuan Zhang, Ki Jeong Lee, William G Richards, Yang Li
Pharmacological doses of fibroblast growth factor (FGF) 21 effectively normalize glucose, lipid and energy homeostasis in multiple animal models with many benefits translating to obese humans with type 2 diabetes. However, a role for FGF21 in the regulation of bile acid metabolism has not been reported. Herein, we demonstrate AAV-mediated FGF21 overexpression in mice increases liver expression of the key bile acid producing enzyme, Cyp7a1, resulting in an increased bile acid pool. Furthermore, in cholecystectomized mice, FGF21-mediated bile acid pool increase led to increased transit of bile acids into colon...
February 2017: EBioMedicine
https://www.readbyqxmd.com/read/28039838/fibroblast-growth-factor-21-and-its-novel-association-with-oxidative-stress
#3
REVIEW
Miguel Ángel Gómez-Sámano, Mariana Grajales-Gómez, Julia María Zuarth-Vázquez, Ma Fernanda Navarro-Flores, Mayela Martínez-Saavedra, Óscar Alfredo Juárez-León, Mariana G Morales-García, Víctor Manuel Enríquez-Estrada, Francisco J Gómez-Pérez, Daniel Cuevas-Ramos
Fibroblast growth factor 21 (FGF21) is an endocrine-member of the FGF family. It is synthesized mainly in the liver, but it is also expressed in adipose tissue, skeletal muscle, and many other organs. It has a key role in glucose and lipid metabolism, as well as in energy balance. FGF21 concentration in plasma is increased in patients with obesity, insulin resistance, and metabolic syndrome. Recent findings suggest that such increment protects tissue from an increased oxidative stress environment. Different types of physical stress, such as strenuous exercising, lactation, diabetic nephropathy, cardiovascular disease, and critical illnesses, also increase FGF21 circulating concentration...
December 22, 2016: Redox Biology
https://www.readbyqxmd.com/read/28017785/hepatic-lipid-metabolism-and-non-alcoholic-fatty-liver-disease-in-aging
#4
Zhenwei Gong, Emir Tas, Shoshana Yakar, Radhika Muzumdar
Aging is associated with dysregulation of glucose and lipid metabolism. Various factors that contribute to the dysregulation include both modifiable (e.g. obesity, insulin resistance) and non-modifiable risk factors (age-associated physiologic changes). Although there is no linear relationship between aging and prevalence of non-alcoholic fatty liver disease, current data strongly suggests that advanced age leads to more severe histological changes and poorer clinical outcomes. Hepatic lipid accumulation could lead to significant hepatic and systemic consequences including steatohepatitis, cirrhosis, impairment of systemic glucose metabolism and metabolic syndrome, thereby contributing to age-related diseases...
December 22, 2016: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/28011645/in-vitro-and-in-vivo-analyses-reveal-profound-effects-of-fibroblast-growth-factor-16-as-a-metabolic-regulator
#5
Ingrid C Rulifson, Patrick Collins, Li Miao, Dana Nojima, Ki Jeong Lee, Miki Hardy, Jamila Gupte, Kelly Hensley, Kim Samayoa, Cynthia Cam, James B Rottman, Mike Ollmann, William G Richards, Yang Li
The discovery of brown adipose tissue (BAT) as a key regulator of energy expenditure has sparked interest in identifying novel soluble factors capable of activating inducible BAT (iBAT) to combat obesity. Using a high content cell-based screen, we identified Fibroblast Growth Factor (FGF) 16 as a potent inducer of several physical and transcriptional characteristics analogous to those of both classical BAT and iBAT. Over-expression of Fgf16 in vivo recapitulated several of our in vitro findings, specifically significant induction of Ucp1 gene and UCP1 protein expression in inguinal white adipose tissue (iWAT), a common site for emergent active iBAT...
December 23, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27808173/metabolic-effects-of-basic-fibroblast-growth-factor-in-streptozotocin-induced-diabetic-rats-a-1-h-nmr-based-metabolomics-investigation
#6
Xiaodong Lin, Liangcai Zhao, Shengli Tang, Qi Zhou, Qiuting Lin, Xiaokun Li, Hong Zheng, Hongchang Gao
The fibroblast growth factors (FGFs) family shows a great potential in the treatment of diabetes, but little attention is paid to basic FGF (bFGF). In this study, to explore the metabolic effects of bFGF on diabetes, metabolic changes in serum and feces were analyzed in the normal rats, the streptozocin (STZ)-induced diabetic rats and the bFGF-treated diabetic rats using a (1)H nuclear magnetic resonance (NMR)-based metabolomic approach. Interestingly, bFGF treatment significantly decreased glucose, lipid and low density lipoprotein/very low density lipoprotein (LDL/VLDL) levels in serum of diabetic rats...
November 3, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27666676/myeloid-cell-specific-lipin-1-deficiency-stimulates-endocrine-adiponectin-fgf15-axis-and-ameliorates-ethanol-induced-liver-injury-in-mice
#7
Jiayou Wang, Chunki Kim, Alvin Jogasuria, Yoonhee Han, Xudong Hu, Jiashin Wu, Hong Shen, Roman Chrast, Brian N Finck, Min You
Lipin-1 is a phosphatidate phosphohydrolase (PAP) required for the generation of diacylglycerol during glycerolipid synthesis, and exhibits dual functions in the regulation of lipid metabolism. Lipin-1 has been implicated in the pathogenesis of alcoholic liver disease (ALD). In the present study, we assessed lipin-1 function in myeloid cells in ALD using a myeloid cell-specific lipin-1 knockout (mLipin-1KO) mouse model. Utilizing the Gao-binge ethanol feeding protocol, matched mLipin-1KO mice and littermate loxP control (WT) mice were pair-fed with either an ethanol-containing diet or an ethanol-free diet (control)...
September 26, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27643551/efficacy-of-a-combination-of-high-and-low-dosage-of-pegylated-fgf-21-in-treatment-of-diabetes-in-db-db-mice
#8
Pengfei Xu, Yingjie Zhang, Liying Song, Mir Hassan Khoso, Junyan Li, Xinghao Jiang, Jinjiao He, Jian Li, Xiaohui Ma, Guiping Ren, Deshan Li
The aim of this study is to explore a new method-high dose starting and low dose maintaining for PEGylated Fibroblast growth factor 21 (pFGF-21) treatment. Db/db mice were initially treated with pFGF-21 of high dose, then treated with pFGF-21 of low doses. The mice were treated with pFGF-21 at initial dose of 1.0mg/kg for 14days, then treated with pFGF-21 at maintenance doses of 0.125/0.250/0.375/0.500mg/kg for 30days. The hypoglycemic and hypolipidemic effects of pFGF-21 of different maintenance doses were compared...
December 2016: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/27555298/loss-of-ctrp1-disrupts-glucose-and-lipid-homeostasis
#9
Susana Rodriguez, Xia Lei, Pia S Petersen, Stefanie Y Tan, Hannah C Little, G William Wong
C1q/TNF-related protein 1 (CTRP1) is a conserved plasma protein of the C1q family with notable metabolic and cardiovascular functions. We have previously shown that CTRP1 infusion lowers blood glucose and that transgenic mice with elevated circulating CTRP1 are protected from diet-induced obesity and insulin resistance. Here, we used a genetic loss-of-function mouse model to address the requirement of CTRP1 for metabolic homeostasis. Despite similar body weight, food intake, and energy expenditure, Ctrp1 knockout (KO) mice fed a low-fat diet developed insulin resistance and hepatic steatosis...
October 1, 2016: American Journal of Physiology. Endocrinology and Metabolism
https://www.readbyqxmd.com/read/27504985/olanzapine-depot-administration-induces-time-dependent-changes-in-adipose-tissue-endocrine-function-in-rats
#10
Katerina Horska, Jana Ruda-Kucerova, Zuzana Babinska, Michal Karpisek, Regina Demlova, Radka Opatrilova, Pavel Suchy, Hana Kotolova
OBJECTIVE: Metabolic adverse effects of atypical antipsychotics (AAP) contribute significantly to increased risk of cardiovascular morbidity and mortality in patients suffering from schizophrenia. Extensive preclinical research has addressed this issue over the past years, though mechanisms underlying these adverse effects of AAP are still not understood completely. Recently, attention is drawn towards the role of adipose tissue metabolism and neurohormonal regulations. METHODS: The aim of this study was to evaluate the time-dependent effects of olanzapine depot administration at clinically relevant dosing on the regulation of energy homeostasis, glucose and lipid metabolism, gastrointestinal and adipose tissue-derived hormones involved in energy balance regulations in female Sprague-Dawley rats...
November 2016: Psychoneuroendocrinology
https://www.readbyqxmd.com/read/27489983/elevated-fgf-21-in-myotonic-dystrophy-type-1-and-mitochondrial-diseases
#11
Emese Lovadi, Márta Csereklyei, Hajnalka Merkli, Krisztina FüLöp, Ágnes Sebők, Veronika Karcagi, Sámuel Komoly, Endre Pál
INTRODUCTION: Human fibroblast growth factor 21 (FGF21) is a regulator of lipid and glucose metabolism. It is expressed in skeletal muscle and may be a sensitive and specific marker for mitochondrial diseases and other neuromuscular disorders. METHODS: Serum FGF21 levels were determined in 71 human samples. Thirty patients with mitochondrial disease, 16 patients with myotonic dystrophy type 1 (DM1), 5 patients with facioscapulohumeral dystrophy, and 20 healthy controls were enrolled...
August 4, 2016: Muscle & Nerve
https://www.readbyqxmd.com/read/27411840/association-of-inflammatory-lipid-and-mineral-markers-with-cardiac-calcification-in-older-adults
#12
Anna E Bortnick, Traci M Bartz, Joachim H Ix, Michel Chonchol, Alexander Reiner, Mary Cushman, David Owens, Eddy Barasch, David S Siscovick, John S Gottdiener, Jorge R Kizer
OBJECTIVE: Calcification of the aortic valve and adjacent structures involves inflammatory, lipid and mineral metabolism pathways. We hypothesised that circulating biomarkers reflecting these pathways are associated with cardiac calcification in older adults. METHODS: We investigated the associations of various biomarkers with valvular and annular calcification in the Cardiovascular Health Study. Of the 5888 participants, up to 3585 were eligible after exclusions for missing biomarker, covariate or echocardiographic data...
July 13, 2016: Heart: Official Journal of the British Cardiac Society
https://www.readbyqxmd.com/read/27270475/postprandial-plasma-concentrations-of-individual-bile-acids-and-fgf-19-in-patients-with-type-2-diabetes
#13
David P Sonne, F Samuel van Nierop, Willem Kulik, Maarten R Soeters, Tina Vilsbøll, Filip K Knop
CONTEXT: Bile acids regulate lipid and carbohydrate metabolism by interaction with membrane or intracellular proteins including the nuclear farnesoid X receptor (FXR). Postprandial activation of ileal FXR leads to secretion of fibroblast growth factor 19 (FGF-19), a gut hormone that may be implicated in postprandial glucose metabolism. OBJECTIVE: To describe postprandial plasma concentrations of 12 individual bile acids and FGF-19 in patients with type 2 diabetes (T2D) and healthy controls...
August 2016: Journal of Clinical Endocrinology and Metabolism
https://www.readbyqxmd.com/read/27262842/hepatokines-and-non-alcoholic-fatty-liver-disease
#14
Dariusz M Lebensztejn, Marta Flisiak-Jackiewicz, Irena Białokoz-Kalinowska, Anna Bobrus-Chociej, Irina Kowalska
Nowadays non-alcoholic fatty liver disease (NAFLD) is becoming the most common chronic liver pathology both in adults and children. NAFLD manifestation ranges from a simple liver steatosis to steatohepatitis (nonalcoholic steatohepatitis - NASH), which may progress to advanced fibrosis, cirrhosis and end-stage liver disease. Due to the coexistence of visceral obesity, insulin resistance and dyslipidemia, NAFLD is considered to be the hepatic manifestation of metabolic syndrome. In recent years, in the pathogenesis of metabolic syndrome, type 2 diabetes mellitus, cardiovascular disease and also NAFLD, more and more attention has been paid to the so-called organokines, proteins with both paracrine or/and endocrine activities...
2016: Acta Biochimica Polonica
https://www.readbyqxmd.com/read/27182456/role-of-serum-biomarkers-in-early-detection-of-non-alcoholic-steatohepatitis-and-fibrosis-in-west-virginian-children
#15
Komal Sodhi, Lucas Bracero, Andrew Feyh, Alexandra Nichols, Krithika Srikanthan, Tariq Latif, Deborah Preston, Joseph I Shapiro, Yoram Elitsur
BACKGROUND: Obesity, an epidemic among West Virginia children, as well as insulin resistance (IR), is well-established contributors to nonalcoholic steatohepatitis (NASH). Progression of NASH can lead to hepatic fibrosis and cirrhosis, making early detection imperative. The standard for diagnosing NASH is histologically via liver biopsy, which is highly invasive and generally contraindicated in children. By studying serum biomarkers associated with NASH, we aim to identify high risk children who can benefit from a less invasive, alternative approach to the early detection of NASH...
February 2016: Journal of Clinical & Cellular Immunology
https://www.readbyqxmd.com/read/27174168/chenodeoxycholic-acid-significantly-impacts-the-expression-of-mirnas-and-genes-involved-in-lipid-bile-acid-and-drug-metabolism-in-human-hepatocytes
#16
Regina Krattinger, Adrian Boström, Serene M L Lee, Wolfgang E Thasler, Helgi B Schiöth, Gerd A Kullak-Ublick, Jessica Mwinyi
AIMS: Bile acids (BAs) are important gut signaling hormones, influencing lipid, glucose, and energy homeostasis. The exact mechanisms behind these effects are not yet fully understood. Lately, they have come to the fore as putative therapeutics in metabolic diseases, such as e.g. nonalcoholic fatty liver disease (NAFLD). We elucidate to what extent BAs impacts on the mRNAome and microRNAome in hepatocytes to gather novel insights into the mechanisms behind metabolic and toxicologic effects of bile acids...
July 1, 2016: Life Sciences
https://www.readbyqxmd.com/read/27148532/roles-of-fgfs-as-paracrine-or-endocrine-signals-in-liver-development-health-and-disease
#17
REVIEW
Nobuyuki Itoh, Yoshiaki Nakayama, Morichika Konishi
The liver plays important roles in multiple processes including metabolism, the immune system, and detoxification and also has a unique capacity for regeneration. FGFs are growth factors that have diverse functions in development, health, and disease. The FGF family now comprises 22 members. Several FGFs have been shown to play roles as paracrine signals in liver development, health, and disease. FGF8 and FGF10 are involved in embryonic liver development, FGF7 and FGF9 in repair in response to liver injury, and FGF5, FGF8, FGF9, FGF17, and FGF18 in the development and progression of hepatocellular carcinoma...
2016: Frontiers in Cell and Developmental Biology
https://www.readbyqxmd.com/read/27061435/mir-149-controls-non-alcoholic-fatty-liver-by-targeting-fgf-21
#18
Junjie Xiao, Dongchao Lv, Yingying Zhao, Xiaoyu Chen, Meiyi Song, Jingqi Liu, Yihua Bei, Fei Wang, Wenzhuo Yang, Changqing Yang
Non-alcoholic fatty liver disease (NAFLD), a lipid metabolism disorder characterized by the accumulation of intrahepatic fat, has emerged as a global public health problem. However, its underlying molecular mechanism remains unclear. We previously have found that miR-149 was elevated in NAFLD induced by high-fat diet mice model, whereas decreased by a 16-week running programme. Here, we reported that miR-149 was increased in HepG2 cells treated with long-chain fatty acid (FFA). In addition, miR-149 was able to promote lipogenesis in HepG2 cells in the absence of FFA treatment...
August 2016: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/27057099/metformin-prevents-fatty-liver-and-improves-balance-of-white-brown-adipose-in-an-obesity-mouse-model-by-inducing-fgf21
#19
Eun Kyung Kim, Seung Hoon Lee, Joo Yeon Jhun, Jae Kyeong Byun, Jeong Hee Jeong, Seon-Young Lee, Jae Kyung Kim, Jong Young Choi, Mi-La Cho
Obesity and its associated metabolic disorders are related to the onset of fatty liver and the balance of white adipose tissue (WAT) and brown adipose tissue (BAT). We hypothesized that metformin, an effective pharmacological treatment for type 2 diabetes, would inhibit white adipogenesis, fatty liver, and metabolic dysfunction. Metformin was treated daily for 14 weeks in a high-fat dieting C57BL/6J mice. Serum biomarkers were analyzed and protein level was assessed using confocal staining or flow cytometry...
2016: Mediators of Inflammation
https://www.readbyqxmd.com/read/27031294/fibroblast-growth-factor-21-as-an-emerging-therapeutic-target-for-type-2-diabetes-mellitus
#20
REVIEW
Wing Yan So, Po Sing Leung
Fibroblast growth factor (FGF) 21 is a distinctive member of the FGF family that functions as an endocrine factor. It is expressed predominantly in the liver, but is also found in adipose tissue and the pancreas. Pharmacological studies have shown that FGF21 normalizes glucose and lipid homeostasis, thereby preventing the development of metabolic disorders, such as obesity and diabetes. Despite growing evidence for the therapeutic potential of FGF21, paradoxical increases of FGF21 in different disease conditions point to the existence of FGF21 resistance...
July 2016: Medicinal Research Reviews
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