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Fgf lipid metabolism

Masakazu Kikai, Hiroyuki Yamada, Noriyuki Wakana, Kensuke Terada, Keita Yamamoto, Naotoshi Wada, Shinichiro Motoyama, Makoto Saburi, Takeshi Sugimoto, Daisuke Irie, Taku Kato, Hiroyuki Kawahito, Takehiro Ogata, Satoaki Matoba
Brown adipose tissue (BAT) has been found as an endocrine organ that maintains metabolic homeostasis; however, the effects on atherosclerosis remain undefined. Here, we investigated the effect of experimental BAT transplantation on atherosclerosis. Interscapular BAT was dissected from wild-type mice and transplanted into the visceral cavity of 12-week-old apoE-/- mice. Oil-red O staining of whole aortas after 3 months of a high-cholesterol diet showed a significant decrease in atherosclerotic lesion area in BAT-transplanted mice by 32% compared with the sham control mice...
February 26, 2018: Biochemical and Biophysical Research Communications
Qiang Li, Qiang Zhao, Chuanzhao Zhang, Peng Zhang, Anbin Hu, Longjuan Zhang, Paul M Schroder, Yi Ma, Zhiyong Guo, Xiaofeng Zhu, Xiaoshun He
Fibroblast growth factor (FGF) has been considered to modulate liver regeneration (LR) after partial hepatectomy (PH) at the tissue level. Previous studies have demonstrated that FGF15 and FGF19 induce the activation of its receptor, FGF receptor 4 (FGFR4), which can promote hepatocellular carcinoma progression and regulate liver lipid metabolism. In this study, we aimed to explore the role of the ileal FGF15/19- hepatic FGFR4 axis in the LR after PH. Male C57BL/6 mice aged 8-12 weeks were partially hepatectomized and assessed for expression of ileal FGF15/19 to hepatic FGFR4 signaling...
February 22, 2018: Journal of Physiology and Biochemistry
Nan Wang, Tong-Yu Xu, Xu Zhang, Jun-Yan Li, Yun-Xin Wang, Xiao-Chen Guo, Si-Ming Li, Wen-Fei Wang, De-Shan Li
Type 2 diabetes mellitus (T2DM) is accompanied by abnormal glucose metabolism and low-grade chronic inflammation. Fibroblast growth factor 21 (FGF-21) is a novel metabolic regulator and can function as an endocrine hormone to regulate glucose and lipid metabolism. Recently, FGF-21 was found to have anti-inflammatory effect, to our knowledge, the effect of FGF-21 on inflammatory state in diabetes has not been elucidated. Here, we use db/db mice as a Type 2 diabetes model to determine whether FGF-21 alleviates inflammatory state while improves hyperglycemia...
February 2, 2018: International Immunopharmacology
Yufei He, Yazhuo Li, Zihong Wei, Xingyan Zhang, Jing Gao, Xiaojie Wang, Xiaokun Li, Weidang Wu, Wei Li, Xiulin Yi, Yong Zeng, Changxiao Liu
As one of the fibroblast growth factor (FGF) superfamily, FGF-21 has been extensivelyinvestigated for its functions and roles since its discovery. It has been demonstrated to be one of key regulators for glucose, and lipid metabolism, and exhibit beneficial effects on cardiovascular disease. However, studies focusing on its pharmacokinetic behavior in vivo as a novel therapeutic agent has not been reported. In the present study, rapid and sensitive analytical approaches including radioactivity assay and assay after precipitation/separation by HPLC were established to determine the content of FGF-21 tagged with 125 I in plasma, tissue and excrement...
February 4, 2018: Drug Testing and Analysis
Magdalene K Montgomery, Ruzaidi Mokhtar, Jacqueline Bayliss, Helena C Parkington, Victor M Suturin, Clinton R Bruce, Matthew J Watt
Lipid droplets are critical for the regulation of lipid metabolism, and dysregulated lipid metabolism contributes to the pathogenesis of several diseases including type 2 diabetes. We generated mice with muscle-specific deletion of the lipid droplet-associated protein, perilipin 5 (PLIN5, Plin5MKO ), and investigated PLIN5's role in regulating skeletal muscle lipid metabolism, intracellular signalling and whole-body metabolic homeostasis. High-fat feeding induced changes in muscle lipid metabolism of Plin5MKO mice, which included increased fatty acid oxidation and oxidative stress, but surprisingly, a reduction in inflammation and endoplasmic reticulum (ER) stress...
January 29, 2018: Diabetes
Yoshichika Miyazaki, Emi Saita, Yoshimi Kishimoto, Susumu Ibe, Toshiki Seki, Kotaro Miura, Norie Suzuki-Sugihara, Yukinori Ikegami, Reiko Ohmori, Kazuo Kondo, Yukihiko Momiyama
AIM: Fibroblast growth factor-21 (FGF-21) is a metabolic regulator with beneficial effects on glucolipid metabolism. Since FGF-21 has lipid-lowering, anti-inflammatory and anti-oxidant properties, it may play a protective role against atherosclerosis. However, blood FGF-21 levels in coronary artery disease (CAD) or peripheral artery disease (PAD) have not been elucidated. METHODS: We measured plasma FGF-21 levels in 417 patients undergoing coronary angiography, who also had ankle-brachial index test for PAD screening...
January 24, 2018: Journal of Atherosclerosis and Thrombosis
Phillipp Hartmann, Katrin Hochrath, Angela Horvath, Peng Chen, Caroline T Seebauer, Cristina Llorente, Lirui Wang, Yazen Alnouti, Derrick E Fouts, Peter Stärkel, Rohit Loomba, Sally Coulter, Christopher Liddle, Ruth T Yu, Lei Ling, Stephen J Rossi, Alex M DePaoli, Michael Downes, Ronald M Evans, David A Brenner, Bernd Schnabl
Alcoholic liver disease is associated with changes in the intestinal microbiota. Functional consequences of alcohol-associated dysbiosis are largely unknown. The aim of this study was to identify a mechanism of how changes in the intestinal microbiota contribute to alcoholic liver disease. Metagenomic sequencing of intestinal contents demonstrated that chronic ethanol feeding in mice is associated with an overrepresentation of bacterial genomic DNA encoding choloylglycine hydrolase, which deconjugates bile acids in the intestine...
November 21, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
Masakazu Kikai, Hiroyuki Yamada, Noriyuki Wakana, Kensuke Terada, Keita Yamamoto, Naotoshi Wada, Shinichiro Motoyama, Makoto Saburi, Takeshi Sugimoto, Daisuke Irie, Taku Kato, Hiroyuki Kawahito, Takehiro Ogata, Satoaki Matoba
Aims: Brown adipose tissue (BAT) has been identified as an endocrine organ that maintains metabolic homeostasis; however, the effects on atherosclerosis remain undefined. Here, we investigated the effect of experimental BAT transplantation on atherosclerosis. Methods and Results: Interscapular BAT was dissected from 12-week-old wild-type mice and transplanted into the visceral cavity of 12-week-old apoE-/- mice. Oil-red O staining of whole aortas after 3 months of a high-cholesterol diet showed a significant decrease in atherosclerotic lesion area in BAT-transplanted mice by 20% compared with the sham control mice...
November 2, 2017: Cardiovascular Research
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 humans that have to be considered before translation from bench to bedside can be successful...
October 1, 2017: Endocrine Reviews
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)...
November 2017: Experimental and Clinical Endocrinology & Diabetes
Li Jiao, Hongying Gan-Schreier, Xingya Zhu, Wang Wei, Sabine Tuma-Kellner, Gerhard Liebisch, Wolfgang Stremmel, Walee Chamulitrat
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...
December 2017: Biochimica et Biophysica Acta
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...
January 9, 2018: Cell Metabolism
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 2017: Neuro Endocrinology Letters
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...
October 15, 2017: Biochemical Pharmacology
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 2017: Archives of Endocrinology and Metabolism
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
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
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
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
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
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