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https://www.readbyqxmd.com/read/29669306/paternal-exercise-protects-mouse-offspring-from-high-fat-diet-induced-type-2-diabetes-risk-by-increasing-skeletal-muscle-insulin-signaling
#1
Danielle Krout, James N Roemmich, Amy Bundy, Rolando A Garcia, Lin Yan, Kate J Claycombe-Larson
Paternal obesity increases, while paternal exercise decreases, offspring obesity and type 2 diabetes (T2D) risk; however, no studies have determined whether a paternal high-fat (HF) diet and exercise interact to alter offspring body weight (BW), adiposity and T2D risk. Three-week-old male C57BL/6 mice were fed a normal-fat (NF) diet (16% fat) or an HF diet (45% fat) and assigned to either voluntary wheel running exercise or cage activity for 3 months prior to mating with NF-diet-fed dams. After weaning, male offspring were fed an NF or HF diet for an additional 3 months...
March 21, 2018: Journal of Nutritional Biochemistry
https://www.readbyqxmd.com/read/29665127/proteomic-analysis-of-serum-and-sputum-analytes-distinguishes-controlled-and-poorly-controlled-asthmatics
#2
Marion T Kasaian, Julie Lee, Agnes Brennan, Spencer I Danto, Kendall E Black, Lori Fitz, Anne E Dixon
BACKGROUND: A major goal of asthma therapy is to achieve disease control, with maintenance of lung function, reduced need for rescue medication, and prevention of exacerbation. Despite current standard of care, up to 70% of patients with asthma remain poorly controlled. Analysis of serum and sputum biomarkers could offer insights into parameters associated with poor asthma control. OBJECTIVE: To identify signatures as determinants of asthma disease control, we performed proteomics using Olink proximity extension analysis...
April 17, 2018: Clinical and Experimental Allergy: Journal of the British Society for Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/29663541/eccentric-exercise-increases-circulating-fibroblast-activation-protein-but-not-bioactive-fibroblast-growth-factor-21-in-healthy-humans
#3
Biraj Parmar, Jo E Lewis, Ricardo J Samms, Francis J P Ebling, Christine C Cheng, Andrew C Adams, Joanne Mallinson, Scott Cooper, Tariq Taylor, Reza Ghasemi, Francis B Stephens, Kostas Tsintzas
NEW FINDINGS: What is the central question of this study? The role of FGF21 as an exercise-induced myokine remains controversial. The aim of this study was to determine whether eccentric exercise would augment the release of FGF21 and/or its regulatory enzyme Fibroblast Activation Protein (FAP) from skeletal muscle tissue into the systemic circulation of healthy human volunteers. What is the main finding and its importance? Eccentric exercise does not release total or bioactive FGF21 from human skeletal muscle...
April 16, 2018: Experimental Physiology
https://www.readbyqxmd.com/read/29661866/reciprocal-effects-of-antiretroviral-drugs-used-to-treat-hiv-infection-on-the-fibroblast-growth-factor-21-%C3%AE-klotho-system
#4
Ricardo Moure, Pere Domingo, Joan Villarroya, Laura Gasa, José M Gallego-Escuredo, Tania Quesada-López, Samantha Morón-Ros, Alberto F Maroto, Gracia M Mateo, Joan C Domingo, Francesc Villarroya, Marta Giralt
Following antiretroviral therapy, HIV-infected patients show increased circulating levels of the antidiabetic hormone fibroblast growth factor-21 (FGF21). In contrast, expression of the FGF21-obligatory co-receptor β-Klotho (KLB) is reduced in target tissues. This situation is comparable to the FGF21 resistance status observed in obesity and type-2 diabetes. Here, we performed the first systematic study of the effects of distinct members of different antiretroviral drug classes on the FGF21/KLB system in human hepatic, adipose, and skeletal muscle cells...
April 16, 2018: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/29660397/a-pharmacology-guided-approach-for-setting-limits-on-product-related-impurities-for-bispecific-antibody-manufacturing
#5
Sharmila Rajan, Junichiro Sonoda, Timothy Tully, Ambrose J Williams, Feng Yang, Frank Macchi, Terry Hudson, Mark Z Chen, Shannon Liu, Nicole Valle, Kyra Cowan, Thomas Gelzleichter
INTRODUCTION: bFKB1 is a humanized bispecific IgG1 antibody, created by conjoining an anti-Fibroblast Growth Factor Receptor 1 (FGFR1) half-antibody to an anti-Klothoβ (KLB) half-antibody, using the knobs-into-holes strategy. bFKB1 acts as a highly selective agonist for the FGFR1/KLB receptor complex and is intended to ameliorate obesity-associated metabolic defects by mimicking the activity of the hormone FGF21. An important aspect of the biologics product manufacturing process is to establish meaningful product specifications regarding the tolerable levels of impurities that copurify with the drug product...
April 13, 2018: Journal of Pharmacological and Toxicological Methods
https://www.readbyqxmd.com/read/29659970/cholic-acid-supplementation-of-a-high-fat-obesogenic-diet-suppresses-hepatic-triacylglycerol-accumulation-in-mice-via-a-fibroblast-growth-factor-21-dependent-mechanism
#6
Siri M Ippagunta, Alexei Kharitonenkov, Andrew C Adams, F Bradley Hillgartner
Background: Supplementation of a high-fat obesogenic diet (HFD) with cholic acid (CA) suppresses the development of obesity, insulin resistance, and hepatic steatosis in mice. Objective: We investigated the role of fibroblast growth factor 21 (FGF21) in mediating the beneficial actions of CA on metabolic syndrome. Methods: Male 7-wk-old wild-type (WT) mice and FGF21 knockout (FGF21KO) mice were fed an HFD for 12 wk followed by a 4-wk period in which the mice were fed the HFD alone or supplemented with 0...
April 1, 2018: Journal of Nutrition
https://www.readbyqxmd.com/read/29657029/the-hormone-fgf21-stimulates-water-drinking-in-response-to-ketogenic-diet-and-alcohol
#7
Parkyong Song, Christoph Zechner, Genaro Hernandez, José Cánovas, Yang Xie, Varun Sondhi, Martin Wagner, Vanessa Stadlbauer, Angela Horvath, Bettina Leber, Ming Chang Hu, Orson W Moe, David J Mangelsdorf, Steven A Kliewer
Alcohol and ketogenic diets increase water consumption. Here, we show that the hormone FGF21 is required for this drinking response in mice. Circulating levels of FGF21 are increased by alcohol consumption in humans and by both alcohol and ketogenic diets in mice. Pharmacologic administration of FGF21 stimulates water drinking behavior in mice within 2 hr. Concordantly, mice lacking FGF21 fail to increase water intake in response to either alcohol or a ketogenic diet. The effect of FGF21 on drinking is mediated in part by SIM1-positive neurons of the hypothalamus and is inhibited by β-adrenergic receptor antagonists...
April 12, 2018: Cell Metabolism
https://www.readbyqxmd.com/read/29653185/sex-differences-in-the-development-of-hepatic-steatosis-in-cafeteria-diet-induced-obesity-in-young-mice
#8
Fabiana Rodrigues Silva Gasparin, Fernando Olinto Carreño, Juliana Moraes Mewes, Eduardo Hideo Gilglioni, Clairce Luzia Salgueiro Pagadigorria, Maria Raquel Marçal Natali, Karina Sayuri Utsunomiya, Rodrigo Polimeni Constantin, Amanda Tomie Ouchida, Carlos Curti, Ingrid C Gaemers, Ronald Petrus Johannes Oude Elferink, Jorgete Constantin, Emy Luiza Ishii-Iwamoto
The present study was planned to improve our understanding about sex differences in the development of hepatic steatosis in cafeteria diet-induced obesity in young mice. Female (FCaf) and male (MCaf) mice fed a cafeteria diet had similar body weight gain and adiposity index, but FCaf had a more extensive steatosis than MCaf. FCaf livers exhibited a higher non-alcoholic fatty liver disease activity score, elevated lipid percentage area (+34%) in Sudan III staining and increased TG content (+25%) compared to MCaf...
April 10, 2018: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29653030/sex-modulates-the-association-of-fibroblast-growth-factor-21-with-end-stage-renal-disease-in-asian-people-with-type-2-diabetes-a-6-3-year-prospective-cohort-study
#9
Jian-Jun Liu, Sylvia Liu, Robin Wm Choo, Shiou Liang Wee, Aimin Xu, Su Chi Lim
AIM: To study whether plasma fibroblast growth factor 21 independently predicts the risk of end-stage renal disease in Asian people with Type 2 diabetes. METHODS: In this prospective cohort study, 1700 Asian people with Type 2 diabetes were followed for a mean of 6.3 years in a regional hospital in Singapore. Incident end-stage renal disease was identified by linkage with a national renal registry. The association of baseline fibroblast growth factor 21 levels with risk of progression to end-stage renal disease was studied using survival analyses...
April 13, 2018: Diabetic Medicine: a Journal of the British Diabetic Association
https://www.readbyqxmd.com/read/29648978/fgf21-protects-the-blood-brain-barrier-by-upregulating-ppar%C3%AE-via-fgfr1-%C3%AE-klotho-following-traumatic-brain-injury
#10
Jun Chen, Jian Hu, Huan Liu, Ye Xiong, Yuchi Zou, Wenting Huang, Mingjie Shao, Jiamin Wu, Li Yu, Xiaojie Wang, Xue Wang, Li Lin
Blood-brain barrier (BBB) disruption and dysfunction result in brain edema, which is responsible for more than half of all deaths after severe traumatic brain injury (TBI). Fibroblast growth factor 21 (FGF21) has a potential neuroprotective function in the brain. However, the effects and underlying possible mechanism of action on BBB integrity following TBI remain unknown. The purpose of the current study was to determine the effects of FGF21 on BBB protection and TBI treatment. The effects of recombinant human FGF21 (rhFGF21) on BBB integrity and on tight junction and adherens junction proteins were investigated both in a TBI mouse model and an in vitro BBB disruption model established with TNF-α-induced human brain microvascular endothelial cells (HBMECs)...
March 6, 2018: Journal of Neurotrauma
https://www.readbyqxmd.com/read/29627377/fgf21-a-liver-hormone-that-inhibits-alcohol-intake-in-mice-increases-in-human-circulation-after-acute-alcohol-ingestion-and-sustained-binge-drinking-at-oktoberfest
#11
Susanna Søberg, Emilie S Andersen, Niels B Dalgaard, Ida Jarlhelt, Nina L Hansen, Nina Hoffmann, Tina Vilsbøll, Anne Chenchar, Michal Jensen, Trisha J Grevengoed, Sam A J Trammell, Filip K Knop, Matthew P Gillum
OBJECTIVE: Excessive alcohol consumption is a leading cause of global morbidity and mortality. However, knowledge of the biological factors that influence ad libitum alcohol intake may be incomplete. Two large studies recently linked variants in the KLB locus with levels of alcohol intake in humans. KLB encodes β-klotho, co-receptor for the liver-derived hormone fibroblast growth factor 21 (FGF21). In mice, FGF21 reduces alcohol intake, and human Fgf21 variants are enriched among heavy drinkers...
March 27, 2018: Molecular Metabolism
https://www.readbyqxmd.com/read/29618013/fgf21-is-associated-with-metabolic-effects-and-treatment-response-in-depressed-bipolar-ii-disorder-patients-treated-with-valproate
#12
Hui Hua Chang, Po See Chen, Yung Wen Cheng, Tzu-Yun Wang, Yen Kuang Yang, Ru-Band Lu
Background: Patients with bipolar disorder are at high risk of metabolic disturbance after mood stabilizer treatment. However, the mediators linking the two conditions remain unknown. In this study, we investigated whether fibroblast growth factor-21 (FGF21) was associated with metabolic effects and treatment response in depressed bipolar disorder patients. Methods: We recruited 78 community-dwelling controls and 137 bipolar disorder patients; the latter were interviewed using the Chinese Version of the Modified Schedule of Affective Disorder and Schizophrenia-Life Time...
April 1, 2018: International Journal of Neuropsychopharmacology
https://www.readbyqxmd.com/read/29615519/fgf21-acts-as-a-negative-regulator-of-bile-acid-synthesis
#13
Michelle M Chen, Clarence Hale, Shanaka Stanislaus, Jing Xu, Murielle M Véniant
Fibroblast growth factor 21 (FGF21) is a potent regulator of glucose and lipid homeostasis in vivo ; its most closely related subfamily member, FGF19, is known to be a critical negative regulator of bile acid synthesis. To delineate whether FGF21 also plays a functional role in bile acid metabolism, we evaluated the effects of short- and long-term exposure to native FGF21 and long-acting FGF21 analogs on hepatic signal transduction, gene expression and enterohepatic bile acid levels in primary hepatocytes and in rodent and monkey models...
May 2018: Journal of Endocrinology
https://www.readbyqxmd.com/read/29608670/parsing-the-potential-neuroendocrine-actions-of-fgf21-in-primates
#14
Matthew P Gillum
Fibroblast growth factor 21 (FGF21), a unique, largely liver-derived, endocrine member of the FGF-superfamily, is often thought of as a fasting factor owing to its induction in rodents during starvation. However, FGF21 is not increased by fasting for periods of <7 days in humans, but instead rises sharply after acute alcohol and sugar intake, and also after several days overfeeding, suggesting another role in states of positive energy balance. In the postingestive state, recent studies suggest that FGF21 may regulate energy intake and discourage consumption of alcohol and sugars, likely through effector circuits in the central nervous system...
March 28, 2018: Endocrinology
https://www.readbyqxmd.com/read/29603684/effects-of-a-novel-selective-peroxisome-proliferator-activated-receptor-%C3%AE-modulator-pemafibrate-k-877-on-hepatic-and-peripheral-glucose-uptake-in-patients-with-hypertriglyceridemia-and-insulin-resistance
#15
Ikuro Matsuba, Ren Matsuba, Shun Ishibashi, Shizuya Yamashita, Hidenori Arai, Koutaro Yokote, Hideki Suganami, Eiichi Araki
AIMS/INTRODUCTION: Pemafibrate (K-877) is a novel selective peroxisome proliferator-activated receptor α modulator (SPPARMα) with potent triglyceride (TG)-lowering and high-density lipoprotein cholesterol-raising effects. We showed that pemafibrate decreased the homeostasis model assessment for insulin resistance (HOMA-IR) in patients with dyslipidemia. To investigate how pemafibrate improves insulin sensitivity, we used a hyperinsulinemic-euglycemic clamp technique to determine the splanchnic and peripheral glucose uptake in patients with hypertriglyceridemia and insulin resistance...
March 30, 2018: Journal of Diabetes Investigation
https://www.readbyqxmd.com/read/29596961/protein-restriction-and-cancer
#16
REVIEW
Jie Yin, Wenkai Ren, Xingguo Huang, Tiejun Li, Yulong Yin
Protein restriction without malnutrition is currently an effective nutritional intervention known to prevent diseases and promote health span from yeast to human. Recently, low protein diets are reported to be associated with lowered cancer incidence and mortality risk of cancers in human. In murine models, protein restriction inhibits tumor growth via mTOR signaling pathway. IGF-1, amino acid metabolic programing, FGF21, and autophagy may also serve as potential mechanisms of protein restriction mediated cancer prevention...
March 26, 2018: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29596655/enhanced-hepatic-ppar%C3%AE-activity-links-glut8-deficiency-to-augmented-peripheral-fasting-responses-in-male-mice
#17
Allyson L Mayer, Yiming Zhang, Emily H Feng, Cassandra B Higgins, Oyin Adenekan, Terri A Pietka, Wandy L Beatty, Brian J DeBosch
The adaptive fasting response is invoked as a promising cardiometabolic and neurodegenerative therapeutic pathway. We and others have defined the carbohydrate transporter, GLUT8, as a critical regulator of hepatic and whole-organism metabolic homeostasis in the overfed and diabetic states. However, the functions of this critical transporter in the physiological fasting response remain poorly understood. Here, we tested the hypothesis that GLUT8 modulates the adaptive hepatic fasting response. We demonstrate that mice with targeted Slc2a8 disruption exhibit enhanced thermogenesis, ketogenesis and peripheral lipid mobilization during fasting...
March 26, 2018: Endocrinology
https://www.readbyqxmd.com/read/29593555/ileal-transposition-surgery-decreases-fat-mass-and-improves-glucose-metabolism-in-diabetic-gk-rats-possible-involvement-of-fgf21
#18
Kemin Yan, Weijie Chen, Huijuan Zhu, Guole Lin, Hui Pan, Naishi Li, Linjie Wang, Hongbo Yang, Meijuan Liu, Fengying Gong
Objective: Ileal transposition (IT) surgery has been reported to improve glucose and lipid metabolism, and fibroblast growth factor 21 (FGF21) is a powerful metabolic regulator. In the present study, we aimed to investigate the effects of IT surgery on metabolism and its possible relationship with the FGF21 signaling pathway in diabetic Goto-Kakizaki (GK) rats. Methods: Ten-week-old male GK rats were subjected to IT surgery with translocation of a 10 cm ileal segment to the proximal jejunum (IT group) or sham surgery without the ileum transposition (Sham-IT group)...
2018: Frontiers in Physiology
https://www.readbyqxmd.com/read/29581470/factors-associated-with-cognitive-impairment-in-elderly-versus-nonelderly-patients-with-metabolic-syndrome-the-different-roles-of-fgf21
#19
Arintaya Phrommintikul, Piangkwan Sa-Nguanmoo, Jirapas Sripetchwandee, Prin Vathesatogkit, Nipon Chattipakorn, Siriporn C Chattipakorn
Increased fibroblast growth factor 21 (FGF21) levels have been found in patients with metabolic syndrome (MetS). MetS is also associated with cognitive decline. However, the correlation between FGF21 and cognitive decline in elderly and nonelderly MetS patients has not been investigated. 116 non-elderly patients (age <65 years old) and 96 elderly patients (≥65 years old) with MetS were enrolled. Blood samples for FGF21 were collected from all participants after 12-hour fasting. Cognitive function was assessed using the Montreal cognitive assessment (MoCA) test...
March 26, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29558502/sustained-effect-of-glucagon-on-body-weight-and-blood-glucose-assessed-by-continuous-glucose-monitoring-in-diabetic-rats
#20
Christina Pedersen, Trine Porsgaard, Maria Thomsen, Mette Marie Rosenkilde, Nikolaj Kulahin Roed
Insulin is a vital part of diabetes treatment, whereas glucagon is primarily used to treat insulin-induced hypoglycemia. However, glucagon is suggested to have a central role in the regulation of body weight, which would be beneficial for diabetic patients. Since the glucagon effect on blood glucose is known to be transient, it is relevant to investigate the pharmacodynamics of glucagon after repeated dosing. In the present study, we used telemetry to continuously measure blood glucose in streptozotocin induced diabetic Sprague-Dawley rats...
2018: PloS One
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