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Fgf lipid metabolism

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https://www.readbyqxmd.com/read/28537053/fibroblast-growth-factor-21-mimetics-for-treating-atherosclerosis
#1
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/28451950/the-role-and-potential-therapeutic-implications-of-the-fibroblast-growth-factors-in-energy-balance-and-type-2-diabetes
#2
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/28337713/the-potential-role-of-fibroblast-growth-factor-21-in-lipid-metabolism-and-hypertension
#3
REVIEW
Zhe Huang, Aimin Xu, Bernard M Y Cheung
Fibroblast growth factor (FGF) 21 belongs to the FGF superfamily that is involved in cell proliferation and differentiation, neural development, angiogenesis, and metabolism. FGF21 requires β-Klotho as a co-receptor. Tissues involved in metabolism such as the liver, adipose tissues, skeletal muscle, and pancreas express FGF21. Starvation increases hepatic expression of FGF21, which then acts centrally to increase hepatic gluconeogenesis. FGF21 also increases fatty acid oxidation. This may be relevant in cold exposure, when expression of FGF21 is induced...
April 2017: Current Hypertension Reports
https://www.readbyqxmd.com/read/28324011/a-novel-fc-fgf21-with-improved-resistance-to-proteolysis-increased-affinity-towards-%C3%AE-klotho-and-enhanced-efficacy-in-mice-and-cynomolgus-monkeys
#4
Shanaka Stanislaus, Randy Hecht, Junming Yie, Todd Hager, Michael Hall, Chris Spahr, Wei Wang, Jennifer Weiszmann, Yang Li, Liying Deng, Dwight Winters, Stephen Smith, Lei Zhou, Yuesheng Li, Murielle M Véniant, Jing Xu
FGF21 is a natural hormone that modulates glucose, lipid, and energy metabolism. Previously, we engineered an Fc fusion FGF21 variant with two mutations, Fc-FGF21(RG), to extend the half-life and reduce aggregation and in vivo degradation of FGF21. We now describe a new variant developed to reduce the extreme C-terminal degradation and improve the binding affinity to β-Klotho. We demonstrate, by introducing one additional mutation located at the C-terminus of FGF21 (A180E) that the new molecule, Fc-FGF21(RGE), has gained many improved attributes...
January 26, 2017: Endocrinology
https://www.readbyqxmd.com/read/28315901/the-effect-of-sitagliptin-on-lipid-metabolism-of-fatty-liver-mice-and-related-mechanisms
#5
Bilin Xu, Tian Shen, Lin Chen, Juan Xia, Cuiping Zhang, Hongping Wang, Ming Yu, Tao Lei
BACKGROUND In clinics, patients with type 2 diabetes complicated with non-alcoholic fatty liver disease (NAFLD) have been shown to receive significant improvements in blood glucose levels, lipid levels, and liver function after sitagliptin treatment, although the mechanism of drug action remains poorly understood. This study investigated the possible mechanism of sitagliptin on lipid metabolism of NAFLD mice. MATERIAL AND METHODS Male C57/BL6 mice were induced for NAFLD via 16 weeks of a high-fat diet, and were treated with 15 mg/kg/day sitagliptin for 16 consecutive weeks...
March 19, 2017: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
https://www.readbyqxmd.com/read/28249286/impact-of-fibroblast-growth-factors-19-and-21-in-bariatric-metabolism
#6
REVIEW
Ashley Patton, Farooq H Khan, Rohit Kohli
BACKGROUND: Bariatric surgery is a popular and effective therapeutic intervention for obesity, which is an abnormal health condition that is prevalent worldwide. Metabolic improvements that precede weight loss after bariatric surgery may be mediated, in part, through the fibroblast growth factor (FGF) 15/19 and FGF21 signaling pathways. Both FGF15/19 and FGF21 are hormone-like members of the FGF family and exert their metabolic effects in an endocrine manner. Enhanced bile acid recycling after bariatric surgery leads to increased circulating levels of FGF15/19 in the distal small intestine...
2017: Digestive Diseases
https://www.readbyqxmd.com/read/28225059/decreased-levels-of-fibroblast-growth-factor-21-are-correlated-with-improved-hypoglycemia-in-patients-with-insulinoma
#7
Xu Li, Haoyong Yu, Jun Yin, Lianxi Li, Jian Zhou, Ming Li, Qing Li, Haibing Chen, Fang Liu, Yuqian Bao, Junfeng Han, Weiping Jia
Fibroblast growth factor-21 (FGF-21) improves insulin sensitivity and lipid metabolism in obese or diabetic animal models and has been proposed as a potential therapeutic agent for treating T2DM, obesity, and their related complications. However, little is known about the changes of FGF21 levels in response to endogenous hyperinsulinemic hypoglycemia. To explore its relationship with parameters of glucose metabolism in patients with insulinoma, eleven subjects with pathological insulinoma and twenty-two healthy subjects were recruited for this study...
February 22, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28106545/the-alterations-of-serum-fgf-21-levels-metabolic-and-body-composition-in-early-breast-cancer-patients-receiving-adjuvant-endocrine-therapy
#8
Murat Akyol, Ahmet Alacacioglu, Leyla Demir, Yuksel Kucukzeybek, Yasar Yildiz, Zehra Gumus, Mete Kara, Tarik Salman, Umut Varol, Halil Taskaynatan, Utku Oflazoglu, Vedat Bayoglu, Mustafa Oktay Tarhan
BACKGROUND: In early breast cancer patients, the effects of hormonal therapy (tamoxifen and aromatase inhibitors) on plasma fibroblast growth factor 21 (FGF-21), lipid levels and body composition have not yet been investigated. Therefore, we aimed to analyze the relationship between FGF-21 and body composition as well as the effects of tamoxifen and aromatase inhibitors on plasma lipid levels, FGF-21, and body composition. METHODS: A total of 72 patients were treated with either tamoxifen or aromatase inhibitors due to their menopausal status after adjuvant radiotherapy...
2017: Cancer Biomarkers: Section A of Disease Markers
https://www.readbyqxmd.com/read/28088388/activation-of-gr-but-not-pxr-by-dexamethasone-attenuated-acetaminophen-hepatotoxicities-via-fgf21-induction
#9
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...
March 1, 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
#10
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
#11
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...
April 2017: Redox Biology
https://www.readbyqxmd.com/read/28017785/hepatic-lipid-metabolism-and-non-alcoholic-fatty-liver-disease-in-aging
#12
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 23, 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
#13
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 16 (FGF16) as a potent inducer of several physical and transcriptional characteristics analogous to those of both "classical" BAT and iBAT. Overexpression of Fgf16 in vivo recapitulated several of our in vitro findings, specifically the significant induction of the Ucp1 gene and UCP1 protein expression in inguinal white adipose tissue (iWAT), a common site for emergent active iBAT...
February 3, 2017: 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
#14
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
#15
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
#16
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
#17
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
#18
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
#19
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...
April 2017: Muscle & Nerve
https://www.readbyqxmd.com/read/27411840/association-of-inflammatory-lipid-and-mineral-markers-with-cardiac-calcification-in-older-adults
#20
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
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