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Image Search Results
Figures S3 and . " width="100%" height="100%">
Journal: Cell Metabolism
Article Title: GDF15 Provides an Endocrine Signal of Nutritional Stress in Mice and Humans
doi: 10.1016/j.cmet.2018.12.016
Figure Lengend Snippet: GDF15 Expression Is Regulated by the Cellular ISR Pathway (A and C) GDF15 mRNA expression (A) and immunoblot analysis (C) of ISR components in wild-type (WT) mouse embryonic fibroblasts (MEFs) treated with vehicle control (Con), cobalt chloride (CoCl2, 625 μM), thapsigargin (Tg, 1 μM), tunicamycin (Tn 5 μg/mL), or L-Histidinol (His, 1 mM) for 6 h. (B) GDF15 mRNA expression in human cell lines (HeLA, HuH7, and A549) treated with Tn (5 μg/mL) for 6 h. (D) GDF15 mRNA expression in WT MEFs pre-treated for 1 h either with the PERK inhibitor GSK2606414 (GSK, 200 nM) or eIF2α inhibitor ISRIB (ISR, 100 nM), then co-treated with Tn (5 μg/mL) for a further 6 h. (E–G) GDF15 mRNA expression (E) in EIF2α Ser51 (SS) or phospho mutant (AA) MEFs or (F) in ATF4 wild-type (WT) or ATF4 knockout (KO) MEFs and (G) in control siRNA and CHOP siRNA transfected WT MEFs treated with Tn (5 μg/mL) for 6 h. (H) Diagram outlining pathway by which GDF15 and FGF21 expression is regulated by TN. mRNA expression is presented as fold expression relative to its respective control treatment for each cell type (set at 1) or TN-treated samples (set as 100) with normalization to HPRT gene expression in MEFs and GAPDH in human cells. Data are expressed as mean ± SD from at least three independent experiments. ∗∗∗ p < 0.001 versus control (con) for (A) and (B), and versus TN stimulated for (D)–(G) by two-tailed Student’s t test. Blots shown are representative of three independent experiments with Calnexin used as a loading control. See also
Article Snippet:
Techniques: Expressing, Western Blot, Control, Mutagenesis, Knock-Out, Transfection, Gene Expression, Two Tailed Test
Journal: Cell Metabolism
Article Title: GDF15 Provides an Endocrine Signal of Nutritional Stress in Mice and Humans
doi: 10.1016/j.cmet.2018.12.016
Figure Lengend Snippet:
Article Snippet:
Techniques: Recombinant, SYBR Green Assay, Protease Inhibitor, Reverse Transcription, Western Blot, Injection, Enzyme-linked Immunosorbent Assay, Control, TaqMan Assay, Software, Sterility, Electrophoresis, Real-time Polymerase Chain Reaction
Journal: Molecular metabolism
Article Title: Fibroblast activation protein (FAP) as a novel metabolic target.
doi: 10.1016/j.molmet.2016.07.003
Figure Lengend Snippet: Figure 2: Chronic FAP inhibition by TB induces metabolic and glycemic benefits and enhances plasma half-life of FGF21 in DIO mice. (AeK) Effects on (A) body weight change, (B) food intake, (C) body composition change, (DeE) intraperitoneal glucose tolerance, (F) plasma insulin, (G) insulin tolerance, (H) plasma cholesterol, (I) total and intact plasma FGF21, (J) body weight-corrected energy expenditure and (K) real-time respiratory quotient of male DIO mice treated daily with vehicle or TB (0.03, 0.1, 0.3 and 1 mg/kg) for 16 days. In D, E, G, J and K, only mice treated with vehicle, 0.3 and 1 mg/kg/day were analyzed. The glucose (D) and insulin (G) tolerance tests were performed in different cohorts of animals at day 7 of treatment. In K, shaded regions represent time during the dark cycle of light. Data are presented as mean SEM; n ¼ 8; *P < 0.05, **P < 0.01, and ***P < 0.001, determined by ANOVA comparing effects following compound administration to vehicle treatment. #P < 0.05, ##P < 0.01, and ###P < 0.001, determined by ANOVA comparing effect following compound administration to vehicle (intact FGF21 value) treatment. In both comparisons, ANOVA was followed by Tukey post hoc multiple comparison analysis to determine statistical significance. Energy expenditure data were analyzed using ANCOVA, with body weight, fat mass and lean mass as covariates. P ¼ 0.002 when compared the highest TB dose (1 mg/kg) to vehicle group. P ¼ 0.003 when comparing vehicle and both TB doses.
Article Snippet: Liquid chromatographyemass spectrometry (LCeMS) In order to check whether mouse FGF21 is susceptible to FAP cleavage, 25 mM
Techniques: Inhibition, Clinical Proteomics, Comparison
Journal: Molecular metabolism
Article Title: Fibroblast activation protein (FAP) as a novel metabolic target.
doi: 10.1016/j.molmet.2016.07.003
Figure Lengend Snippet: Figure 3: The metabolic and glycemic benefits of FAP inhibition are blunted in FGF21del mice. (AeE) Effects on (A) body weight change, (B) body composition, (C) fasting blood glucose and (DeE) oral glucose tolerance of male FGF21del mice treated daily with vehicle or TB (0.3 mg/kg) for 7 days. Data are presented as mean SEM; n ¼ 8; *P < 0.05, **P < 0.01, and ***P < 0.001, determined by ANOVA comparing effects following compound administration to vehicle treatment. #P < 0.05, ##P < 0.01, and ###P < 0.001, determined by ANOVA comparing effect of FGF21 ablation to wild type mice. In both comparisons, ANOVA was followed by Tukey post hoc multiple comparison analysis to determine statistical significance.
Article Snippet: Liquid chromatographyemass spectrometry (LCeMS) In order to check whether mouse FGF21 is susceptible to FAP cleavage, 25 mM
Techniques: Inhibition, Comparison
Journal: Molecular metabolism
Article Title: Fibroblast activation protein (FAP) as a novel metabolic target.
doi: 10.1016/j.molmet.2016.07.003
Figure Lengend Snippet: Figure 4: Chronic FAP inhibition by TB does not have any metabolic influence and does not alter plasma half-life of FGF21 in lean mice. (AeD) Effects on (A) body weight, (B) food intake, (C) body composition change and (D) total and intact plasma FGF21 of male lean mice treated daily with vehicle or TB (0.3, 1 and 3 mg/kg) for 12 days. (E) Effect of recombinant FAP on FGF21 cleavage in vitro. hFGF21 was incubated with recombinant human FAP in the presence or absence of TB for the indicated times in PBS buffer. The products of the enzymatic reaction were resolved on SDS-PAGE and detected with total, N- and C-terminal specific FGF21 antibodies in Western blots. Data are presented as mean SEM; n ¼ 8; *P < 0.05, **P < 0.01, and ***P < 0.001, determined by ANOVA comparing effects following compound administration to vehicle treatment. ANOVA was followed by Tukey post hoc multiple comparison analysis to determine statistical significance.
Article Snippet: Liquid chromatographyemass spectrometry (LCeMS) In order to check whether mouse FGF21 is susceptible to FAP cleavage, 25 mM
Techniques: Inhibition, Clinical Proteomics, Recombinant, In Vitro, Incubation, SDS Page, Western Blot, Comparison
Journal: Endocrinology
Article Title: Dietary Intake Regulates White Adipose Tissues Angiogenesis via Liver Fibroblast Growth Factor 21 in Male Mice.
doi: 10.1210/endocr/bqaa244
Figure Lengend Snippet: Figure 1. Fasting induced adipose-specific VEGF expression and liver Fgf21 expression. Twelve-week-old male C57BL/6J mice were either fed with chow diets ad libitum or fasting for various time periods (6 h, 12 h, and 24 h) as indicated. (A) Serum VEGF levels and (B) the mRNA expression of Vegfa in epididymal WAT (eWAT) (B), subcutaneous iWAT (C), interscapular BAT (D), liver (E), and muscle (F) as determined by real-time PCR ana- lysis. The protein levels of VEGF in eWAT (G) and iWAT (H) as determined by western blot; (I) serum FGF21 levels as determined by enzyme-linked immunosorbent assay; and real-time transcription PCR analysis for Fgf21 mRNA expression levels of liver (J), eWAT (K), iWAT (L), BAT (M), and muscle (N). Serum FFA (O) and ketone bodies (P) levels. Data are mean ± SEM; n = 6/group. Statistical significance was evaluated by 1-way ANOVA with Tukey’s test for multiple comparisons to determine differences between each group. Labeled means without a common letter differ, P < 0.05. Abbreviations: BAT, brown adipose tissue; eWAT, epididymal white adipose tissue; FFA, free fatty acid; FGF21, fibroblast growth factor 21; iWAT, in- guinal white adipose tissue; VEGF, vascular endothelial growth factor.
Article Snippet:
Techniques: Expressing, Real-time Polymerase Chain Reaction, Lysis, Western Blot, Enzyme-linked Immunosorbent Assay, Labeling
Journal: Endocrinology
Article Title: Dietary Intake Regulates White Adipose Tissues Angiogenesis via Liver Fibroblast Growth Factor 21 in Male Mice.
doi: 10.1210/endocr/bqaa244
Figure Lengend Snippet: Figure 2. FGF21 promoted expression and accumulation of VEGF in WAT. The relative mRNA abundance of Vegfa in tissue, adipocytes and stromal vascular fraction isolated from eWAT (A) and iWAT (B) at fed or 24 h of fasting. Twelve-week-old male WT (FGF21fl/fl) and FGF21 LKO mice were fasted for 24 h; the Vegfa mRNA expression in eWAT and iWAT (C). Quantitative reverse transcription PCR analysis for Vegfa mRNA expression in eWAT (D), iWAT (E), and BAT (F) at the indicated time points after tail vein injection of rmFGF21 (1 mg/kg). The protein levels of VEGF at various time points after mice receiving a delivery of rmFGF21 with tail vein injection in eWAT (G) and iWAT (H). n = 6/group. Statistical significance was evaluated by unpaired Student’s t test. *P < 0.05, **P < 0.01, versus control; labeled means without a common letter differ, P < 0.05. Abbreviation: SCV, stromal vascular fraction.
Article Snippet:
Techniques: Expressing, Isolation, Reverse Transcription, Injection, Control, Labeling
Journal: Endocrinology
Article Title: Dietary Intake Regulates White Adipose Tissues Angiogenesis via Liver Fibroblast Growth Factor 21 in Male Mice.
doi: 10.1210/endocr/bqaa244
Figure Lengend Snippet: Figure 3. Intermittent fasting induced adipose-VEGF expression and angiogenesis depend on liver FGF21 signaling. Mice were fed with HFD ad lib- itum or time-restricted access to food for 16 weeks. HA means WT mice eating a high-fat diet with ad libitum, HT means WT mice eating a high-fat diet with time-restricted access to food, KOHA means FGF21 LKO mice eating a high-fat diet with ad libitum, KOHT means FGF21 LKO mice eating a HFD with time-restricted access to food. (A) Schematic illustration of the experimental design. (B) Body weight. (C) Representative HT mice were remarkably leaner than the HA mice. (D) Body composition was evaluated by EchoMRI. (E) Serum FGF21 levels as determined by enzyme-linked im- munosorbent assay. (F) A representative macroscopic image illustrating increased vascularization in iWAT of HT mice, compared to HA mice but not in FGF21 LKO mice. (G) Real-time quantitative PCR analysis for mRNA expression levels of Vegfa in eWAT and iWAT. Representative protein levels for VEGF in eWAT (G) and iWAT (I). (J) Immunofluorescence staining of CD31 (scale bar, 100 mm) in eWAT and iWAT, illustrating IF increased vascular- ization in WT mice but not in FGF21 LKO mice. Data are mean ± SEM; n = 6–8/group. Statistical significance was evaluated by the 2-way ANOVA test and the Tukey’s test for multiple comparisons to determine differences between each group. HA vs HT, *P < 0.05, **P < 0.01; labeled means without a common letter differ, P < 0.05.
Article Snippet:
Techniques: Expressing, Real-time Polymerase Chain Reaction, Immunofluorescence, Staining, Labeling
Journal: Endocrinology
Article Title: Dietary Intake Regulates White Adipose Tissues Angiogenesis via Liver Fibroblast Growth Factor 21 in Male Mice.
doi: 10.1210/endocr/bqaa244
Figure Lengend Snippet: Figure 4. Liver-FGF21 is required for intermittent fasting-induced metabolic benefits. Mice were fed with HFD ad libitum or time-restricted access to food for 16 weeks. (A) O2 consumption (VO2), (B) CO2 production (VCO2). (C and D) GTT shows normal glucose tolerance in HT mice but not for FGF21 LKO mice. (E) Serum insulin levels. real-time quantitative PCR analysis for mRNA expression levels of browning related genes (F), UCP-1 protein level (G) and immunohistochemical staining (H) of UCP-1 in iWAT. (I) The expression of pro-inflammatory cytokines (Tnfα and IL1-β) in eWAT. (J) A working model of dietary intake regulating iWAT browning via FGF21 signaling. Data are mean ± SEM; n = 6–8/group. Statistical significance was evaluated by the 2-way ANOVA test and the Tukey’s test for multiple comparisons to determine differences between each group. *P < 0.05, **P < 0.01; labeled means without a common letter differ, P < 0.05.
Article Snippet:
Techniques: Real-time Polymerase Chain Reaction, Expressing, Immunohistochemical staining, Staining, Labeling
Journal: Physiological Reports
Article Title: Identification of FGF21 ‐inducing rare sugars that reduces sugar appetite in male BL /6 mice
doi: 10.14814/phy2.70618
Figure Lengend Snippet: Identification of FGF21‐inducing rare sugars and their effects on blood glucose. (a–d) FGF21 level of mouse primary hepatocytes treated for 24 h with vehicle (distilled water‐negative control) or 25 mM D‐glucose, D‐fructose (positive control), or rare sugars (46 samples). n = 3 mice. (e) Plasma FGF21 levels over 24 h after gastric gavage of vehicle (distilled water), D‐glucose, D‐tagatose, D‐allulose, or D‐sorbitol at 5 g/kg in nine‐week‐old male WT mice with ad libitum access to normal chow (NC) diet. n = 4 mice per group. (f) Area under the curve (AUC) over 24 h of data in (e). n = 4 mice per group. (g) Blood glucose levels of the mice receiving the same dose in (e) of either vehicle (distilled water), D‐glucose, D‐tagatose, D‐allulose, or D‐sorbitol after 16 h fasting. n = 4 mice per group. Statistical analyses were done by one‐way ANOVA for (a–d, f) and repeated measures ANOVA for (e, g), followed by Tukey's HSD test. ** p < 0.01; **** p < 0.0001.
Article Snippet:
Techniques: Negative Control, Positive Control, Clinical Proteomics
Journal: Physiological Reports
Article Title: Identification of FGF21 ‐inducing rare sugars that reduces sugar appetite in male BL /6 mice
doi: 10.14814/phy2.70618
Figure Lengend Snippet: FGF21‐inducing rare sugars activated oxytocin neurons of paraventricular nucleus of hypothalamus in BL/6 mice. (a–e) Immunostaining of mice brain after gastric gavage with either (a) vehicle (distilled water) or 5 g/kg body weight of D‐glucose (b), D‐tagatose (c), D‐allulose (d), or D‐sorbitol (e). Blue arrow ( ) indicates c‐Fos‐positive oxytocin neurons, shown by dark brown spot on the light brown neurons ( ). Magenta arrow ( ) indicates c‐Fos‐negative oxytocin neurons, shown by light brown anti‐oxytocin staining ( ). n = 4 mice per group. Scale bar represents 100 μ m. (f) Percentage of activated oxytocin neurons (c‐Fos positive oxytocin neurons) from the total of PVH oxytocin neurons in the mice receiving either vehicle (distilled water), D‐glucose, or FGF21‐inducing rare sugars in (a–e). Data are presented as box‐whiskers in (f), where the middle line represents median, bottom/ top edges represent 25th/75th percentile of the data, and whiskers represent maximum and minimum value of the data. Statistical analyses were done by one‐way ANOVA, followed by Dunnett's test.
Article Snippet:
Techniques: Immunostaining, Staining
Journal: Physiological Reports
Article Title: Identification of FGF21 ‐inducing rare sugars that reduces sugar appetite in male BL /6 mice
doi: 10.14814/phy2.70618
Figure Lengend Snippet: Intragastric administration of FGF21‐inducing rare sugars reduced sucrose preference in BL/6 mice. (a–c) 50 mM sucrose intake in mice receiving 5 g/kg body weight of D‐allulose (a), D‐tagatose (b), or D‐sorbitol (c). (d–f) sucrose preference of the same mice in (a–c). n = 10 mice per group for (a, d) and n = 5 mice per group for (b, c, e, f). Data are presented as box‐whiskers, where the middle line represents the median, bottom/top edges represent the 25th/75th percentile of the data, and whiskers represent the maximum and minimum value of the data. Statistical analyses were done by Student's paired t ‐test between “pre” and “post” of each treatment.
Article Snippet:
Techniques:
Journal: Physiological Reports
Article Title: Identification of FGF21 ‐inducing rare sugars that reduces sugar appetite in male BL /6 mice
doi: 10.14814/phy2.70618
Figure Lengend Snippet: Mixing FGF21‐inducing rare sugars into sucrose solution reduced solution intake and preference in BL/6 mice. (a–c) Intake of 100 mM (final concentration) sucrose solution that was mixed with either vehicle (distilled water), 600 mM (final concentration) of D‐glucose, or 600 mM (final concentration) of D‐allulose (a), D‐tagatose (b), or D‐sorbitol (c). (d–f) Sucrose preference of the same mice in (a–c). n = 6 mice per group. Data are presented as box‐whiskers, where the middle line represents the median, bottom/top edges represent the 25th/75th percentile of the data, and whiskers represent the maximum and minimum value of the data. Statistical analyses were done by repeated measures ANOVA, followed by Tukey's HSD test.
Article Snippet:
Techniques: Concentration Assay
Journal: Toxicology
Article Title: Alcoholic fatty liver is enhanced in CYP2A5 knockout mice: the role of the PPARα-FGF21 axis
doi: 10.1016/j.tox.2017.01.016
Figure Lengend Snippet: Chronic ethanol induces FGF21 in Cyp2a5+/+ mice but does not in Cyp2a5−/− mice. (A) Serum FGF21 (N=5). (B) Liver expression of FGF21 and PPARα by Western blotting analysis. (C) Quantitation of Western blots (N=4). *P<0.05, compared to Cyp2a5+/+ Control Group. Cont, Control; EtOH, Ethanol.
Article Snippet: Some mice were daily injected
Techniques: Expressing, Western Blot, Quantitation Assay, Control
Journal: Toxicology
Article Title: Alcoholic fatty liver is enhanced in CYP2A5 knockout mice: the role of the PPARα-FGF21 axis
doi: 10.1016/j.tox.2017.01.016
Figure Lengend Snippet: Chronic ethanol induces FGF21 in Nrf2+/+ mice more than in Nrf2−/− mice. (A) Western blots. (B) Quantitation of Western blots (N=3). *P<0.05, compared to Nrf2+/+ Control Group; # P<0.05, compared to Nrf2−/− Control Group; & P<0.05, compared with Nrf2+/+ Ethanol group. Cont, Control; EtOH, Ethanol.
Article Snippet: Some mice were daily injected
Techniques: Western Blot, Quantitation Assay, Control
Journal: Toxicology
Article Title: Alcoholic fatty liver is enhanced in CYP2A5 knockout mice: the role of the PPARα-FGF21 axis
doi: 10.1016/j.tox.2017.01.016
Figure Lengend Snippet: Recombinant FGF21 blunts ethanol-induced hypertriglyceridemia (HTG) in Pparα−/− mice. (A) Ethanol induction of FGF21 was blunted in Pparα−/− mice (N=5). (B) rFGF21 blunted ethanol-induced elevation of liver TG in WT mice but not in Pparα−/− mice (N=5). (C) rFGF21 blunted ethanol-induced HTG in Pparα−/− mice (N=5). (D) Ethanol induction of CYP2E1 and CYP2A5 was not affected in both Pparα+/+ and Pparα−/− mice (N=5). *P<0.05, compared to Control Group. # P<0.05, compared to WT Ethanol Group. $ P<0.05, compared to WT Control Group. ^ P<0.05, compared with PPARα KO Ethanol group. E+F, ethanol plus rFGF21; WT, wild-type; PPARα KO, Pparα−/−.
Article Snippet: Some mice were daily injected
Techniques: Recombinant, Control
Journal: Toxicology
Article Title: Alcoholic fatty liver is enhanced in CYP2A5 knockout mice: the role of the PPARα-FGF21 axis
doi: 10.1016/j.tox.2017.01.016
Figure Lengend Snippet: Alcoholic fatty liver is enhanced in Fgf21alb-cre mice but is not in Fr1alb-cre mice. (A) Ethanol induction of FGF21 was blunted in Fgf21alb-cre mice but was not in Fr1alb-cre mice (N=5). (B) H&E staining in liver sections shows that alcoholic fatty liver was enhanced in Fgf21alb-cre mice but not in Fr1alb-cre mice. (C) Steatosis scores (N=5). (D) Liver TG contents (N=5). *P<0.05, compared to Fr1fl/fl Control Group. # P<0.05, compared to Fgf21fl/fl Ethanol Group. ^ P<0.05, compared with Fgf21fl/fl control group. $ P<0.05, compared to Fr1alb-cre Control Group. @ P<0.05, compared to Fr1alb-cre Control Group. Cont, Control; EtOH, Ethanol.
Article Snippet: Some mice were daily injected
Techniques: Staining, Control
Journal: Toxicology
Article Title: Alcoholic fatty liver is enhanced in CYP2A5 knockout mice: the role of the PPARα-FGF21 axis
doi: 10.1016/j.tox.2017.01.016
Figure Lengend Snippet: Alcoholic fatty liver is more pronounced in Pparα−/−/Cyp2a5−/− mice than in Pparα+/+/Cyp2a5−/− mice. (A) Ethanol induction of FGF21 was blunted in Pparα−/−/Cyp2a5−/− mice (N=4). (B) H&E staining in liver sections shows that alcoholic fatty liver was more pronounced in Pparα−/−/Cyp2a5−/− mice than in Pparα+/+/Cyp2a5−/− mice. (C) Steatosis scores (N=5). (D) Liver TG contents (N=5). *P<0.05, compared to Pparα+/+/Cyp2a5−/− Control Group. # P<0.05, compared to Pparα−/−/Cyp2a5−/− Control Group. & P<0.05, compared to Pparα+/+/Cyp2a5−/− Ethanol Group. Cont, Control; EtOH, Ethanol.
Article Snippet: Some mice were daily injected
Techniques: Staining, Control
Journal: Lipids in Health and Disease
Article Title: Dietary moderately oxidized oil induces expression of fibroblast growth factor 21 in the liver of pigs
doi: 10.1186/1476-511X-11-34
Figure Lengend Snippet: Characteristics and performance data of the primers used for qPCR analysis and reference gene-stability measure M
Article Snippet: Concentrations of FGF21 in plasma and liver were quantified by an ELISA assay kit highly specific to porcine
Techniques:
Journal: Lipids in Health and Disease
Article Title: Dietary moderately oxidized oil induces expression of fibroblast growth factor 21 in the liver of pigs
doi: 10.1186/1476-511X-11-34
Figure Lengend Snippet: Relative mRNA abundance of FGF21 in the liver (A) and protein concentration of FGF21 in the liver (B) and plasma (C) of pigs fed either a fresh fat or an oxidized fat . Bars represent mean ± SD (n = 12/group), and are expressed as fold of fresh fat group. *Significantly ( P < 0.05) and # in tendency ( P < 0.1) different from pigs fed the fresh fat. FF, fresh fat group; FGF21, fibroblast growth factor 21; OF, oxidized fat group
Article Snippet: Concentrations of FGF21 in plasma and liver were quantified by an ELISA assay kit highly specific to porcine
Techniques: Protein Concentration, Clinical Proteomics