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https://www.readbyqxmd.com/read/28437237/proteomics-in-hypothermia-as-adjunctive-therapy-in-patients-with-st-segment-elevation-myocardial-infarction-a-chill-mi-substudy
#1
Moman A Mohammad, Marco Noc, Irene Lang, Michael Holzer, Peter Clemmensen, Ulf Jensen, Bernhard Metzler, David Erlinge
Cardiovascular and inflammatory biomarkers in therapeutic hypothermia have been studied in cardiac arrest, but data on patients with ST-segment elevation myocardial infarction (STEMI) treated with therapeutic hypothermia are currently unavailable. A multiplex proximity extension assay allowed us to measure 157 cardiovascular disease (CVD) and inflammatory disease-related biomarkers in patients from the international, multicenter, and randomized trial; CHILL-myocardial infarction (MI) and to explore the associations of cardiovascular and inflammatory biomarkers...
March 2, 2017: Therapeutic Hypothermia and Temperature Management
https://www.readbyqxmd.com/read/28429779/metabolism-adipose-and-nonadipose-effects-of-fgf21-delineated
#2
David Holmes
No abstract text is available yet for this article.
April 21, 2017: Nature Reviews. Endocrinology
https://www.readbyqxmd.com/read/28424617/targeting-bile-acid-receptors-discovery-of-a-potent-and-selective-farnesoid-x-receptor-agonist-as-a-new-lead-in-the-pharmacological-approach-to-liver-diseases
#3
Carmen Festa, Simona De Marino, Adriana Carino, Valentina Sepe, Silvia Marchianò, Sabrina Cipriani, Francesco S Di Leva, Vittorio Limongelli, Maria C Monti, Angela Capolupo, Eleonora Distrutti, Stefano Fiorucci, Angela Zampella
Bile acid (BA) receptors represent well-defined targets for the development of novel therapeutic approaches to metabolic and inflammatory diseases. In the present study, we report the generation of novel C-3 modified 6-ethylcholane derivatives. The pharmacological characterization and molecular docking studies for the structure-activity rationalization, allowed the identification of 3β-azido-6α-ethyl-7α-hydroxy-5β-cholan-24-oic acid (compound 2), a potent and selective FXR agonist with a nanomolar potency in transactivation assay and high efficacy in the recruitment of SRC-1 co-activator peptide in Alfa Screen assay...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28422956/chronic-activation-of-ppar%C3%AE-with-fenofibrate-reduces-autophagic-proteins-in-the-liver-of-mice-independent-of-fgf21
#4
Eunjung Jo, Songpei Li, Qingning Liang, Xinmei Zhang, Hao Wang, Terence P Herbert, Trisha A Jenkins, Aimin Xu, Ji-Ming Ye
Autophagy is a catabolic mechanism to degrade cellular components to maintain cellular energy levels during starvation, a condition where PPARα may be activated. Here we report a reduced autophagic capacity in the liver following chronic activation of PPARα with fenofibrate (FB) in mice. Chronic administration of the PPARα agonist FB substantially reduced the levels of multiple autophagy proteins in the liver (Atg3, Agt4B, Atg5, Atg7 and beclin 1) which were associated with a decrease in the light chain LC3II/LC3I ratio and the accumulation of p62...
2017: PloS One
https://www.readbyqxmd.com/read/28422755/%C3%AE-klotho-deficiency-protects-against-obesity-through-a-crosstalk-between-liver-microbiota-and-brown-adipose-tissue
#5
Emmanuel Somm, Hugues Henry, Stephen J Bruce, Sébastien Aeby, Marta Rosikiewicz, Gerasimos P Sykiotis, Mohammed Asrih, François R Jornayvaz, Pierre Damien Denechaud, Urs Albrecht, Moosa Mohammadi, Andrew Dwyer, James S Acierno, Kristina Schoonjans, Lluis Fajas, Gilbert Greub, Nelly Pitteloud
β-Klotho (encoded by Klb) is the obligate coreceptor mediating FGF21 and FGF15/19 signaling. Klb-/- mice are refractory to beneficial action of pharmacological FGF21 treatment including stimulation of glucose utilization and thermogenesis. Here, we investigated the energy homeostasis in Klb-/- mice on high-fat diet in order to better understand the consequences of abrogating both endogenous FGF15/19 and FGF21 signaling during caloric overload. Surprisingly, Klb-/- mice are resistant to diet-induced obesity (DIO) owing to enhanced energy expenditure and BAT activity...
April 20, 2017: JCI Insight
https://www.readbyqxmd.com/read/28415887/amelioration-of-late-onset-hepatic-steatosis-in-idh2-deficient-mice
#6
Su Jeong Lee, Hanvit Cha, Hyunjin Kim, Jin Hyup Lee, Jeen-Woo Park
Nonalcoholic fatty liver disease (NAFLD) has a high prevalence in the general population and can evolve into nonalcoholic steatohepatosis (NASH), cirrosis, and complications such as liver failure and hepatocellular carcinoma. Recently, we reported that mitochondrial NADP(+)-dependent isocitrate dehydrogenase, encoded by the IDH2, plays an important role in the regulation of redox balance and oxidative stress levels which are tightly associated with intermediary metabolism and energy production. In the present study, we showed that in mice targeted disruption of IDH2 attenuates age-associated hepatic steatosis by the activation of p38/cJun NH2-terminal kinase (JNK) and p53, presumably induced by the elevation of mitochondrial reactive oxygen species (ROS), which in turn resulted in the suppression of hepatic lipogenesis and inflammation via the upregulation of fibroblast growth factor 21 (FGF21) and the inhibition of NFκB signaling pathways...
April 18, 2017: Free Radical Research
https://www.readbyqxmd.com/read/28414763/enhanced-offspring-predisposition-to-steatohepatitis-with-maternal-high-fat-diet-is-associated-with-epigenetic-and-microbiome-alterations
#7
Umesh D Wankhade, Ying Zhong, Ping Kang, Maria Alfaro, Sree V Chintapalli, Keshari M Thakali, Kartik Shankar
OBJECTIVE: Non-alcoholic fatty liver disease (NAFLD) is an important co-morbidity associated with obesity and a precursor to steatohepatitis. However, the contributions of gestational and early life influences on development of NAFLD and NASH remain poorly appreciated. METHODS: Two independent studies were performed to examine whether maternal over-nutrition via exposure to high fat diet (HFD) leads to exacerbated hepatic responses to post-natal HFD and methionine choline deficient (MCD) diets in the offspring...
2017: PloS One
https://www.readbyqxmd.com/read/28413172/the-effects-of-metformin-on-fibroblast-growth-factor-19-21-and-fibroblast-growth-factor-receptor-1-in-high-fat-diet-and-streptozotocin-induced-diabetic-rats
#8
Yan Wang, Ningning Dang, Pei Sun, Jin Xia, Chunxue Zhang, Shuguang Pang
To understand metformin’s effects on fibroblast growth factors (FGFs) and fibroblast growth factor receptor 1 (FGFR1), we investigated circulating fibroblast growth factor-19 (FGF19), FGF21 levels, and FGFR1 in type 2 diabetes mellitus (T2DM). In addition, protein kinase B (Akt) signaling pathway was detected to explain the possible mechanisms. T2DM was induced by feeding rats with high-fat diet for 11 weeks, followed by a low dose of streptozotocin (STZ, 30-35 mg/kg, intraperitoneally). Control rats (Con) were fed on a normal chow; diabetic rats (DM) were fed on high-fat diet supplemented with or without metformin (METF) for 12 weeks (500 mg・kg(-1)・d(-1))...
April 11, 2017: Endocrine Journal
https://www.readbyqxmd.com/read/28404815/the-hepatokine-fgf21-is-crucial-for-peroxisome-proliferator-activated-receptor-%C3%AE-agonist-induced-amelioration-of-metabolic-disorders-in-obese-mice
#9
Tsuyoshi Goto, Mariko Hirata, Yumeko Aoki, Mari Iwase, Haruya Takahashi, Minji Kim, Yongjia Li, Huei-Fen Jheng, Wataru Nomura, Nobuyuki Takahashi, Chu-Sook Kim, Rina Yu, Shigeto Seno, Hideo Matsuda, Megumi Aizawa-Abe, Ken Ebihara, Nobuyuki Itoh, Teruo Kawada
Obesity causes excess fat accumulation in white adipose tissues (WAT) and also in other insulin-responsive organs such as the skeletal muscle, increasing the risk for insulin resistance, which can lead to obesity-related metabolic disorders. Peroxisome proliferator-activated receptor-α (PPARα) is a master regulator of fatty acid oxidation, whose activator is known to improve hyperlipidemia. However, the molecular mechanisms underlying PPARα activator-mediated reduction in adiposity and improvement of metabolic disorders are largely unknown...
April 12, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28391633/comparisons-of-cardioprotective-efficacy-between-fibroblast-growth-factor-21-and-dipeptidyl-peptidase-4-inhibitor-in-pre-diabetic-rats
#10
Pongpan Tanajak, Piangkwan Sa-Nguanmoo, Nattayaporn Apaijai, Xiaojie Wang, Guang Liang, Xiaokun Li, Chao Jiang, Siriporn C Chattipakorn, Nipon Chattipakorn
AIMS: Comparative efficacy between fibroblast growth factor 21 (FGF21) and vildagliptin on metabolic regulation, cardiac mitochondrial function, heart rate variability (HRV) and left ventricular (LV) function is not known. We hypothesized that FGF21 and vildagliptin share a similar efficacy in improving these parameters in high-fat diet (HFD) induced obese-insulin resistant rats. METHODS: Twenty-four male Wistar rats were fed with either a normal diet (ND) or a HFD for 12 weeks...
April 9, 2017: Cardiovascular Therapeutics
https://www.readbyqxmd.com/read/28385800/an-exome-chip-association-analysis-in-chinese-reveals-a-functional-missense-variant-of-gckr-that-regulates-fgf21-levels
#11
Chloe Yy Cheung, Clara S Tang, Aimin Xu, Chi-Ho Lee, Ka-Wing Au, Lin Xu, Carol Hy Fong, Kelvin Hm Kwok, Wing-Sun Chow, Yu-Cho Woo, Michele Yuen, Stacey S Cherny, JoJo Hai, Bernard My Cheung, Kathryn Tan, Tai-Hing Lam, Hung-Fat Tse, Pak-Chung Sham, Karen Sl Lam
Fibroblast growth factor 21 (FGF21) is increasingly recognized as an important metabolic regulator of glucose homeostasis. Here, we conducted an exome-chip association analysis by genotyping 5169 Chinese individuals from a community-based cohort and two clinic-based cohorts. A custom Asian Exome-chip was used to detect genetic determinants influencing circulating FGF21 levels. Single-variant association analysis interrogating 70,444 single nucleotide polymorphisms identified a novel locus, GCKR, significantly associated with circulating FGF21 levels at genome-wide significance...
April 6, 2017: Diabetes
https://www.readbyqxmd.com/read/28384648/regulation-of-the-jmjd3-kdm6b-histone-demethylase-in-glioblastoma-stem-cells-by-stat3
#12
Maureen M Sherry-Lynes, Sejuti Sengupta, Shreya Kulkarni, Brent H Cochran
The growth factor and cytokine regulated transcription factor STAT3 is required for the self-renewal of several stem cell types including tumor stem cells from glioblastoma. Here we show that STAT3 inhibition leads to the upregulation of the histone H3K27me2/3 demethylase Jmjd3 (KDM6B), which can reverse polycomb complex-mediated repression of tissue specific genes. STAT3 binds to the Jmjd3 promoter, suggesting that Jmjd3 is a direct target of STAT3. Overexpression of Jmjd3 slows glioblastoma stem cell growth and neurosphere formation, whereas knockdown of Jmjd3 rescues the STAT3 inhibitor-induced neurosphere formation defect...
2017: PloS One
https://www.readbyqxmd.com/read/28380381/fgf21-regulates-metabolism-through-adipose-dependent-and-independent-mechanisms
#13
Lucas D BonDurant, Magdalene Ameka, Meghan C Naber, Kathleen R Markan, Sharon O Idiga, Michael R Acevedo, Susan A Walsh, David M Ornitz, Matthew J Potthoff
FGF21 is an endocrine hormone that regulates energy homeostasis and insulin sensitivity. The mechanism of FGF21 action and the tissues responsible for these effects have been controversial, with both adipose tissues and the central nervous system having been identified as the target site mediating FGF21-dependent increases in insulin sensitivity, energy expenditure, and weight loss. Here we show that, while FGF21 signaling to adipose tissue is required for the acute insulin-sensitizing effects of FGF21, FGF21 signaling to adipose tissue is not required for its chronic effects to increase energy expenditure and lower body weight...
April 4, 2017: Cell Metabolism
https://www.readbyqxmd.com/read/28374855/fibroblast-growth-factor-21-assisted-by-elevated-glucose-activates-paraventricular-nucleus-nucb2-nesfatin-1-neurons-to-produce-satiety-under-fed-states
#14
Putra Santoso, Masanori Nakata, Kazuhiro Shiizaki, Zhang Boyang, Kumari Parmila, Zesemdorj Otgon-Uul, Koshi Hashimoto, Tetsurou Satoh, Masatomo Mori, Makoto Kuro-O, Toshihiko Yada
Fibroblast growth factor 21 (FGF21), liver-derived hormone, exerts diverse metabolic effects, being considered for clinical application to treat obesity and diabetes. However, its anorexigenic effect is debatable and whether it involves the central mechanism remains unclarified. Moreover, the neuron mediating FGF21's anorexigenic effect and the systemic energy state supporting it are unclear. We explored the target neuron and fed/fasted state dependence of FGF21's anorexigenic action. Intracerebroventricular (ICV) injection of FGF21 markedly suppressed food intake in fed mice with elevated blood glucose...
April 4, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28374748/fasting-induced-hormonal-regulation-of-lysosomal-function
#15
Liqun Chen, Ke Wang, Aijun Long, Liangjie Jia, Yuanyuan Zhang, Haiteng Deng, Yu Li, Jinbo Han, Yiguo Wang
Lysosomes are centers for nutrient sensing and recycling that allow mammals to adapt to starvation. Regulation of lysosome dynamics by internal nutrient signaling is well described, but the mechanisms by which external cues modulate lysosomal function are unclear. Here, we describe an essential role of the fasting-induced hormone fibroblast growth factor 21 (FGF21) in lysosome homeostasis in mice. Fgf21 deficiency impairs hepatic lysosomal function by blocking transcription factor EB (TFEB), a master regulator of lysosome biogenesis and autophagy...
April 4, 2017: Cell Research
https://www.readbyqxmd.com/read/28371258/n-3-polyunsaturated-fatty-acids-increase-hepatic-fibroblast-growth-factor-21-sensitivity-via-a-ppar%C3%AE-%C3%AE-klotho-pathway
#16
Wenqi Yang, Xu Chen, Yan Liu, Ming Chen, Xinwei Jiang, Tianran Shen, Qing Li, Yan Yang, Wenhua Ling
SCOPE: Fibroblast growth factor 21 (FGF21) participated in fish oil-mediated hepatic lipid-regulation and anti-inflammatory effects in high-fat diet fed-mice. However, fish oil supplementation did not significantly increase FGF21 protein levels. Whether fish oil-induced benefits in the liver are related to hepatic FGF21 sensitivity remains unclear. METHODS AND RESULTS: Male C57BL/6J mice were fed a low-fat diet (LFD), a high-fat diet (HFD) or a fish oil-supplemented high-fat diet (FOD) for 12 weeks...
March 30, 2017: Molecular Nutrition & Food Research
https://www.readbyqxmd.com/read/28359360/postprandial-changes-in-glucose-oxidation-and-insulin-sensitivity-in-metabolic-syndrome-influence-of-fibroblast-growth-factor-21-and-vitamin-d-status
#17
Kaveri Pathak, Mario J Soares, Yun Zhao, Anthony P James, Jillian L Sherriff, Philip Newsholme
OBJECTIVE: Metabolic inflexibility due to insulin resistance has been reported in metabolic syndrome (MetS). Fibroblast growth factor 21 (FGF21) and vitamin D status may improve insulin sensitivity. The aim of this study was to investigate glucose-induced thermogenesis and oxidation in MetS, and to examine whether changes in FGF21 or prevailing vitamin D status modulated defined metabolic parameters. METHODS: Forty-eight overweight and obese older adults (14 men, 34 women; ages 51 ± 15 y) were studied...
May 2017: Nutrition
https://www.readbyqxmd.com/read/28350786/methylation-of-mylk3-gene-promoter-region-a-biomarker-to-stratify-surgical-care-in-ovarian-cancer-in-a-multicentre-study
#18
David L Phelps, Jane V Borley, Kirsty J Flower, Roberto Dina, Silvia Darb-Esfahani, Ioana Braicu, Jalid Sehouli, Christina Fotopoulou, Charlotte S Wilhelm-Benartzi, Hani Gabra, Joseph Yazbek, Jayanta Chatterjee, Jacey Ip, Harun Khan, Marina-Therese Likos-Corbett, Robert Brown, Sadaf Ghaem-Maghami
BACKGROUND: Survival benefit from surgical debulking of ovarian cancer (OC) is well established, but some women, despite total macroscopic clearance of disease, still have poor prognosis. We aimed to identify biomarkers to predict benefit from conventional surgery. METHODS: Clinical data from women debulked for high-stage OC were analysed (Hammersmith Hospital, London, UK; 2001-2014). Infinium's HumanMethylation27 array interrogated tumour DNA for differentially methylated CpG sites, correlated to survival, in patients with the least residual disease (RD; Hammersmith Array)...
March 28, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/28337713/the-potential-role-of-fibroblast-growth-factor-21-in-lipid-metabolism-and-hypertension
#19
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/28336912/fgf21-regulates-t-cell-development-in-the-neonatal-and-juvenile-thymus
#20
Yoshiaki Nakayama, Yuki Masuda, Hiroya Ohta, Tomohiro Tanaka, Miwa Washida, Yo-Ichi Nabeshima, Ayumi Miyake, Nobuyuki Itoh, Morichika Konishi
We have previously shown that Fibroblast growth factor 21 (Fgf21) is expressed in the thymus as well as in the liver. In line with this expression profile, Fgf21 was recently reported to protect against ageing-related thymic senescence by improving the function of thymic epithelial cells (TECs). However, the function of Fgf21 in the juvenile thymus remained to be elucidated. We investigated the physiological roles of Fgf21 in the juvenile thymus and found that young Fgf21 knockout mice, but not β-Klotho knockout mice nor adult Fgf21 knockout mice, showed a significant reduction in the percentage of single-positive CD4(+) and CD8(+) thymocytes without obvious alteration in TECs...
March 23, 2017: Scientific Reports
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