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https://www.readbyqxmd.com/read/28938407/fibroblast-growth-factor-21-metabolic-role-in-mice-and-men
#1
Harald Staiger, Michaela Keuper, Lucia Berti, Martin Hrabe de Angelis, Hans-Ulrich Häring
Since its identification in 2000, the interest of scientists in the hepatokine fibroblast growth factor (FGF) 21 has tremendously grown, and still remains high, due to a wealth of very robust data documenting this factor's favorable effects on glucose and lipid metabolism in mice. For more than ten years now, intense in vivo and ex vivo experimentation addressed the physiological functions of FGF21 in humans as well as its pathophysiological role and pharmacological effects in human metabolic disease. This work produced a comprehensive collection of data revealing overlaps in FGF21 expression and function but also significant differences between mice and men that have to be considered before translation from bench to bedside can be successful...
July 28, 2017: Endocrine Reviews
https://www.readbyqxmd.com/read/28931175/fibroblast-growth-factor-21-in-patients-with-acromegaly
#2
Jowita Halupczok-Żyła, Aleksandra Jawiarczyk-Przybyłowska, Marek Skrzypski, Mathias Z Strowski, Marek Bolanowski
Introduction The goal of the study was to investigate fibroblast growth factor-21 (FGF-21) levels in acromegalic patients in relation to the disease activity and to compare them with controls. Further, we aimed to evaluate the associations between FGF-21 and random growth hormone (GH), insulin-like growth factor-1 (IGF-1), metabolic and anthropometric parameters. Materials and methods The study group consisted of 50 acromegalic patients divided into 3 subgroups on the basis of disease activity (AA - active acromegaly, CD - controlled disease, CA - cured acromegaly)...
September 20, 2017: Experimental and Clinical Endocrinology & Diabetes
https://www.readbyqxmd.com/read/28888832/ageing-sensitized-by-ipla2%C3%AE-deficiency-induces-liver-fibrosis-and-intestinal-atrophy-involving-suppression-of-homeostatic-genes-and-alteration-of-intestinal-lipids-and-bile-acids
#3
Li Jiao, Hongying Gan-Schreier, Xingya Zhu, Wang Wei, Sabine Tuma-Kellner, Gerhard Liebisch, Wolfgang Stremmel, WaleeChamulitrat
Ageing is a major risk factor for various forms of liver and gastrointestinal (GI) disease and genetic background may contribute to the pathogenesis of these diseases. Group VIA phospholipase A2 or iPLA2β is a homeostatic PLA2 by playing a role in phospholipid metabolism and remodeling. Global iPLA2β(-/-) mice exhibit aged-dependent phenotypes with body weight loss and abnormalities in the bone and brain. We have previously reported the abnormalities in these mutant mice showing susceptibility for chemical-induced liver injury and colitis...
September 6, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28867301/nonalcoholic-fatty-liver-disease-as-a-nexus-of-metabolic-and-hepatic-diseases
#4
REVIEW
Varman T Samuel, Gerald I Shulman
NAFLD is closely linked with hepatic insulin resistance. Accumulation of hepatic diacylglycerol activates PKC-ε, impairing insulin receptor activation and insulin-stimulated glycogen synthesis. Peripheral insulin resistance indirectly influences hepatic glucose and lipid metabolism by increasing flux of substrates that promote lipogenesis (glucose and fatty acids) and gluconeogenesis (glycerol and fatty acid-derived acetyl-CoA, an allosteric activator of pyruvate carboxylase). Weight loss with diet or bariatric surgery effectively treats NAFLD, but drugs specifically approved for NAFLD are not available...
August 29, 2017: Cell Metabolism
https://www.readbyqxmd.com/read/28759185/serum-fgf21-in-girls-with-anorexia-nervosa-comparison-to-normal-weight-and-obese-female-adolescents
#5
Agata Mikolajczak, Joanna M Oswiecimska, Elzbieta Swietochowska, Wojciech Roczniak, Katarzyna T Ziora
BACKGROUND: Fibroblast growth factor 21 (FGF21) is a hepatokine, myokine and adipokine of a potent influence to energy homeostasis. Data according its serum concentrations in AN are contradictory. OBJECTIVES: Analysis of serum FGF21 in girls with acute anorexia nervosa and comparison the results with normal weight and obese female adolescents considering their nutritional status, carbohydrate and lipid metabolism. METHODS: Serum FGF21 concentrations were evaluated using commercially available ELISA kit in 32 Polish girls with restrictive AN (AN), 29 girls with obesity (O) and 21 healthy controls (C)...
July 2, 2017: Neuro Endocrinology Letters
https://www.readbyqxmd.com/read/28756207/pregnane-x-receptor-pxr-deficiency-improves-high-fat-diet-induced-obesity-via-induction-of-fibroblast-growth-factor-15-fgf15-expression
#6
Li-Yang Zhao, Jia-Yi Xu, Zhe Shi, Neal A Englert, Shu-Yun Zhang
Obesity has become a significant global health problem, and is a high risk factor for a variety of metabolic diseases. Fibroblast growth factor (FGF) 15 plays an important role in the regulation of metabolism. Xenobiotic-sensing nuclear receptors pregnane X receptor (PXR/NR1I2) and constitutive androstane receptor (CAR/NR1I3) play important roles in xenobiotic detoxification and metabolism, and also are involved in the regulation of energy metabolism. However, the effects that PXR and CAR have on the regulation of FGF15 are unknown...
July 27, 2017: Biochemical Pharmacology
https://www.readbyqxmd.com/read/28724055/bone-turnover-after-bariatric-surgery
#7
Thalita Lima Melo, Leila Froeder, Leandro da Cunha Baia, Ita Pfeferman Heilberg
Objective: The aim of the present study was to evaluate parameters of bone and mineral metabolism after bariatric surgery. Subjects and methods: This sectional study included data from medical records from 61 bariatric surgery (BS) patients (minimum period of 6 months after the procedure) and from 30 class II and III obese patients as a control group (Cont), consisting of daily dietary intake of macronutrients, calcium and sodium, serum 25(OH)D and parathyroid hormone (PTH) and other biochemical serum and urinary parameters...
July 13, 2017: Archives of Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28552719/regulation-of-longevity-by-fgf21-interaction-between-energy-metabolism-and-stress-responses
#8
REVIEW
Antero Salminen, Kai Kaarniranta, Anu Kauppinen
Fibroblast growth factor 21 (FGF21) is a hormone-like member of FGF family which controls metabolic multiorgan crosstalk enhancing energy expenditure through glucose and lipid metabolism. In addition, FGF21 acts as a stress hormone induced by endoplasmic reticulum stress and dysfunctions of mitochondria and autophagy in several tissues. FGF21 also controls stress responses and metabolism by modulating the functions of somatotropic axis and hypothalamic-pituitary-adrenal (HPA) pathway. FGF21 is a potent longevity factor coordinating interactions between energy metabolism and stress responses...
August 2017: Ageing Research Reviews
https://www.readbyqxmd.com/read/28537053/fibroblast-growth-factor-21-mimetics-for-treating-atherosclerosis
#9
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...
June 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
#10
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
#11
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-toward-%C3%AE-klotho-and-enhanced-efficacy-in-mice-and-cynomolgus-monkeys
#12
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
Fibroblast growth factor (FGF) 21 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...
May 1, 2017: Endocrinology
https://www.readbyqxmd.com/read/28315901/the-effect-of-sitagliptin-on-lipid-metabolism-of-fatty-liver-mice-and-related-mechanisms
#13
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
#14
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
#15
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
#16
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
#17
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
#18
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
#19
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
#20
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...
November 5, 2017: Molecular and Cellular Endocrinology
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