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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
#1
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/28288167/erythropoietin-epo-ameliorates-obesity-and-glucose-homeostasis-by-promoting-thermogenesis-and-endocrine-function-of-classical-brown-adipose-tissue-bat-in-diet-induced-obese-mice
#2
Kazuki Kodo, Satoru Sugimoto, Hisakazu Nakajima, Jun Mori, Ikuyo Itoh, Shota Fukuhara, Keiichi Shigehara, Taichiro Nishikawa, Kitaro Kosaka, Hajime Hosoi
Erythropoietin (EPO), clinically used as a hematopoietic drug, has received much attention due to its nonhematopoietic effects. EPO reportedly has beneficial effects on obesity and diabetes mellitus. We investigated whether interscapular brown adipose tissue (iBAT: main part of classical BAT) could play a role in EPO's anti-obesity and anti-diabetic effects in diet-induced obese mice. Four-week-old male C57BL/6J mice were fed a high-fat diet (HFD-Con), and half were additionally given an intraperitoneal injection of recombinant human EPO (200 IU/kg) (HFD-EPO) thrice a week for four weeks...
2017: PloS One
https://www.readbyqxmd.com/read/28287425/the-relationship-between-mitochondrial-respiratory-chain-activities-in-muscle-and-metabolites-in-plasma-and-urine-a-retrospective-study
#3
Corinne Alban, Elena Fatale, Abed Joulani, Polina Ilin, Ann Saada
The relationship between 114 cases with decreased enzymatic activities of mitochondrial respiratory chain (MRC) complexes I-V (C I-V) in muscle and metabolites in urine and plasma was retrospectively examined. Less than 35% disclosed abnormal plasma amino acids and acylcarnitines, with elevated alanine and low free carnitine or elevated C4-OH-carnitine as the most common findings, respectively. Abnormal urine organic acids (OA) were detected in 82% of all cases. In CI and CII defects, lactic acid (LA) in combination with other metabolites was the most common finding...
March 10, 2017: Journal of Clinical Medicine
https://www.readbyqxmd.com/read/28273637/fgf21-exerts-comparable-pharmacological-efficacy-with-adalimumab-in-ameliorating-collagen-induced-rheumatoid-arthritis-by-regulating-systematic-inflammatory-response
#4
Dan Yu, Xianlong Ye, Ruixiang Che, Qiang Wu, Jianying Qi, Liying Song, Xiaochen Guo, Shengqi Zhang, Hongsong Wu, Guiping Ren, Deshan Li
Previous studies have reported that Fibroblast growth factor 21 (FGF21) can regulate inflammation and may play an important role in inflammatory and immune-mediated diseases, such as autoimmune diseases. Adalimumab is one of the clinically effective anti-rheumatoid arthritis (RA) drugs. The aim of this study was to compare the therapeutic efficacy of FGF21 and Adalimumab on collagen-induced arthritis (CIA) model mice. Mice with CIA were subcutaneously treated with FGF21 or Adalimumab at dose of 1mgkg(-1)d(-1), respectively...
March 5, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28259034/negative-correlation-between-cerebrospinal-fluid-fgf21-levels-and-bdi-scores-in-male-chinese-subjects
#5
Yanlong Liu, Meiling Wang, Xiaohua Tan, Xiaofang Wang, Xiaoyu Yang, Jian Xiao, Xiaokun Li, Fan Wang
Fibroblast growth factor 21 (FGF21) is an important metabolic regulator of glucose homeostasis and lipid metabolism. Recently, FGF21 has been shown to play a robust neuroprotective role and act as a mediator of the effects of mood stabilizers. In the present study, we measured the concentration of FGF21 in human cerebrospinal fluid (CSF) and investigated the relationship of FGF21 levels with depression and anxiety emotions. Sixty-seven Chinese volunteers were recruited from Beijing Jishuitan Hospital. A significant negative association was found between CSF FGF21 levels and Beck Depression Inventory (BDI) scores in male subjects...
January 27, 2017: Psychiatry Research
https://www.readbyqxmd.com/read/28256636/elevated-fibroblast-growth-factor-21-fgf21-in-obese-insulin-resistant-states-is-normalised-by-the-synthetic-retinoid-fenretinide-in-mice
#6
Nicola Morrice, George D Mcilroy, Seshu R Tammireddy, Jennifer Reekie, Kirsty D Shearer, Mary K Doherty, Mirela Delibegović, Phillip D Whitfield, Nimesh Mody
Fibroblast growth factor 21 (FGF21) has emerged as an important beneficial regulator of glucose and lipid homeostasis but its levels are also abnormally increased in insulin-resistant states in rodents and humans. The synthetic retinoid Fenretinide inhibits obesity and improves glucose homeostasis in mice and has pleotropic effects on cellular pathways. To identify Fenretinide target genes, we performed unbiased RNA-seq analysis in liver from mice fed high-fat diet ± Fenretinide. Strikingly, Fgf21 was the most downregulated hepatic gene...
March 3, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28249286/impact-of-fibroblast-growth-factors-19-and-21-in-bariatric-metabolism
#7
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
#8
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/28223503/mitochondrial-energy-deficiency-leads-to-hyperproliferation-of-skeletal-muscle-mitochondria-and-enhanced-insulin-sensitivity
#9
Ryan M Morrow, Martin Picard, Olga Derbeneva, Jeremy Leipzig, Meagan J McManus, Gilles Gouspillou, Sébastien Barbat-Artigas, Carlos Dos Santos, Russell T Hepple, Deborah G Murdock, Douglas C Wallace
Diabetes is associated with impaired glucose metabolism in the presence of excess insulin. Glucose and fatty acids provide reducing equivalents to mitochondria to generate energy, and studies have reported mitochondrial dysfunction in type II diabetes patients. If mitochondrial dysfunction can cause diabetes, then we hypothesized that increased mitochondrial metabolism should render animals resistant to diabetes. This was confirmed in mice in which the heart-muscle-brain adenine nucleotide translocator isoform 1 (ANT1) was inactivated...
March 7, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28217097/feedback-activation-of-basic-fibroblast-growth-factor-signaling-via-the-wnt-%C3%AE-catenin-pathway-in-skin-fibroblasts
#10
Xu Wang, Yuting Zhu, Congcong Sun, Tao Wang, Yingjie Shen, Wanhui Cai, Jia Sun, Lisha Chi, Haijun Wang, Na Song, Chao Niu, Jiayi Shen, Weitao Cong, Zhongxin Zhu, Yuanhu Xuan, Xiaokun Li, Litai Jin
Skin wound healing is a complex process requiring the coordinated behavior of many cell types, especially in the proliferation and migration of fibroblasts. Basic fibroblast growth factor (bFGF) is a member of the FGF family that promotes fibroblast migration, but the underlying molecular mechanism remains elusive. The present RNA sequencing study showed that the expression levels of several canonical Wnt pathway genes, including Wnt2b, Wnt3, Wnt11, T-cell factor 7 (TCF7), and Frizzled 8 (FZD8) were modified by bFGF stimulation in fibroblasts...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28199833/fgf21-administration-suppresses-retinal-and-choroidal-neovascularization-in-mice
#11
Zhongjie Fu, Yan Gong, Raffael Liegl, Zhongxiao Wang, Chi-Hsiu Liu, Steven S Meng, Samuel B Burnim, Nicholas J Saba, Thomas W Fredrick, Peyton C Morss, Ann Hellstrom, Saswata Talukdar, Lois E H Smith
Pathological neovascularization, a leading cause of blindness, is seen in retinopathy of prematurity, diabetic retinopathy, and age-related macular degeneration. Using a mouse model of hypoxia-driven retinal neovascularization, we find that fibroblast growth factor 21 (FGF21) administration suppresses, and FGF21 deficiency worsens, retinal neovessel growth. The protective effect of FGF21 against neovessel growth was abolished in adiponectin (APN)-deficient mice. FGF21 administration also decreased neovascular lesions in two models of neovascular age-related macular degeneration: very-low-density lipoprotein-receptor-deficient mice with retinal angiomatous proliferation and laser-induced choroidal neovascularization...
February 14, 2017: Cell Reports
https://www.readbyqxmd.com/read/28199304/adipose-derived-circulating-mirnas-regulate-gene-expression-in-other-tissues
#12
Thomas Thomou, Marcelo A Mori, Jonathan M Dreyfuss, Masahiro Konishi, Masaji Sakaguchi, Christian Wolfrum, Tata Nageswara Rao, Jonathon N Winnay, Ruben Garcia-Martin, Steven K Grinspoon, Phillip Gorden, C Ronald Kahn
Adipose tissue is a major site of energy storage and has a role in the regulation of metabolism through the release of adipokines. Here we show that mice with an adipose-tissue-specific knockout of the microRNA (miRNA)-processing enzyme Dicer (ADicerKO), as well as humans with lipodystrophy, exhibit a substantial decrease in levels of circulating exosomal miRNAs. Transplantation of both white and brown adipose tissue-brown especially-into ADicerKO mice restores the level of numerous circulating miRNAs that are associated with an improvement in glucose tolerance and a reduction in hepatic Fgf21 mRNA and circulating FGF21...
February 23, 2017: Nature
https://www.readbyqxmd.com/read/28191538/lipodystrophy-hiv-related-and-fgf21-a-new-marker-to-follow-the-progression-of-lipodystrophy
#13
Stefano Benedini, Livio Luzi
Recently new evidence about fibroblast growth factor 21 (FGF21) highlights the opportunities to use this molecule in new pharmaceutical formulations to combat type 2 diabetes and metabolic syndrome. It is well known that HIV is per se a condition of insulin resistance and in particular the patient with HIV-related lipodystrophy has a condition strictly related to metabolic syndrome. Lipodystrophy is associated with severe metabolic side effects, including dyslipidemia, hepatic insulin resistance, and lipid oxidation impairment...
December 1, 2016: Journal of Translational Internal Medicine
https://www.readbyqxmd.com/read/28191311/supplemental-smartamine-m-in-higher-energy-diets-during-the-prepartal-period-improves-hepatic-biomarkers-of-health-and-oxidative-status-in-holstein-cows
#14
Mario Vailati-Riboni, Johan S Osorio, Erminio Trevisi, Daniel Luchini, Juan J Loor
BACKGROUND: Feeding higher-energy prepartum is a common practice in the dairy industry. However, recent data underscore how it could reduce performance, deepen negative energy balance, and augment inflammation and oxidative stress in fresh cows. We tested the effectiveness of rumen-protected methionine in preventing the negative effect of feeding a higher-energy prepartum. Multiparous Holstein cows were fed a control lower-energy diet (CON, 1.24 Mcal/kg DM; high-straw) during the whole dry period (~50 d), or were switched to a higher-energy (OVE, 1...
2017: Journal of Animal Science and Biotechnology
https://www.readbyqxmd.com/read/28188284/glucagon-and-insulin-cooperatively-stimulate-fibroblast-growth-factor-21-gene-transcription-by-increasing-the-expression-of-activating-transcription-factor-4
#15
Kimberly M Alonge, Gordon P Meares, F Bradley Hillgartner
Previous studies have shown that glucagon cooperatively interacts with insulin to stimulate hepatic fibroblast growth factor 21 (FGF21) gene expression. Here, we investigated the mechanism by which glucagon and insulin increased FGF21 gene transcription in primary hepatocyte cultures. Transfection analyses demonstrated that glucagon plus insulin induction of FGF21 transcription was conferred by two activating transcription factor 4 (ATF4) binding sites in the FGF21 gene. Glucagon plus insulin stimulated a 5-fold increase in ATF4 protein abundance, and knockdown of ATF4 expression suppressed the ability of glucagon plus insulin to increase FGF21 expression...
February 10, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28184000/angptl6-expression-is-coupled-with-mitochondrial-oxphos-function-to-regulate-adipose-fgf21
#16
Seul Gi Kang, Hyon-Seung Yi, Min Jeong Choi, Min Jeong Ryu, Saetbyel Jung, Hyo Kyun Chung, Joon Young Chang, Yong Kyung Kim, Seong Eun Lee, Hyeon-Woo Kim, Hoil Choi, Dong Seok Kim, Ju Hee Lee, Koon Soon Kim, Hyun Jin Kim, Chul-Ho Lee, Yuichi Oike, Minho Shong
Recent studies revealed that the inhibition of mitochondrial oxidative phosphorylation (OXPHOS) is coupled with the mitochondrial unfolded protein response, thereby stimulating the secretion of non-cell-autonomous factors, which may control systemic energy metabolism and longevity. However, the nature and roles of non-cell-autonomous factors induced in adipose tissue in response to reduced OXPHOS function remain to be clarified in mammals. CR6-interacting factor 1 (CRIF1) is an essential mitoribosomal protein for the intramitochondrial production of mtDNA-encoded OXPHOS subunits...
February 9, 2017: Journal of Endocrinology
https://www.readbyqxmd.com/read/28181108/circulating-levels-of-fibroblast-growth-factor-21-in-early-stage-diabetic-kidney-disease
#17
A Esteghamati, A Khandan, A Momeni, A Behdadnia, A Ghajar, M S Nikdad, S Noshad, M Nakhjavani, M Afarideh
AIMS/PURPOSE: Fibroblast growth factor 21 (FGF21), a hepatoadipokine with pleiotropic metabolic regulatory actions, is emerging as a novel biomarker of progressive nephropathy. We sought to evaluate circulating FGF21 and its association with clinical and biochemical characteristics as well as the urinary albumin excretion (UAE) rates in a population of patients with type 2 diabetes (T2D) with or without microalbuminuria and their matched healthy controls. METHODS: Cross-sectionally, 130 consecutive individuals comprising patients with T2D with (n = 44) or without (n = 44) microalbuminuria and their healthy controls (n = 42) were recruited for analysis...
February 8, 2017: Irish Journal of Medical Science
https://www.readbyqxmd.com/read/28143735/pharmacological-efficacy-of-fgf21-analogue-liraglutide-and-insulin-glargine-in-treatment-of-type-2-diabetes
#18
Xianlong Ye, Jianying Qi, Dan Yu, Yunzhou Wu, Shenglong Zhu, Shujie Li, Qiang Wu, Guiping Ren, Deshan Li
Fibroblast growth factor 21 (FGF21) is a promising regulator of glucose and lipid metabolism with multiple beneficial effects including hypoglycemic and lipid-lowering. Previous studies have reported that FGF21 is expected to become a new drug for treatment of diabetes. Liraglutide and insulin glargine are the two representative anti-diabetic biological drugs. In the current study, we aim to compare the long-term pharmacological efficacy of mFGF21 (an FGF21 analogue), liraglutide and insulin glargine in type 2 diabetic db/db mice...
April 2017: Journal of Diabetes and its Complications
https://www.readbyqxmd.com/read/28139438/fgf21-deficiency-is-associated-with-childhood-obesity-insulin-resistance-and-hypoadiponectinaemia-the-bcams-study
#19
G Li, J Yin, J Fu, L Li, S F A Grant, C Li, M Li, J Mi, M Li, S Gao
OBJECTIVE: Fibroblast growth factor 21 (FGF21) exerts beneficial effects on metabolic homoeostasis and has been reported to be regulated by adiponectin, leptin and resistin. However, while an association between increased circulating FGF21 and metabolic disorders has been reported in adults, paediatric-specific data are lacking. DESIGN AND METHODS: This study investigated the relationship between FGF21 levels and obesity, insulin resistance (IR), the metabolic syndrome (MetS) and adipokines (adiponectin, leptin and resistin) in a cohort of 3231 Chinese youngsters aged 6-18...
January 27, 2017: Diabetes & Metabolism
https://www.readbyqxmd.com/read/28133364/pancreas-fgf21-gets-the-juices-flowing
#20
David Holmes
No abstract text is available yet for this article.
January 30, 2017: Nature Reviews. Endocrinology
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