murine fgf21 protein  (MedChemExpress)

Journal: Nature Communications

Article Title: Hepatocyte SLCO4C1 is a cAMP uptake transporter for inhibiting lipogenesis and a therapeutic target for MASLD

doi: 10.1038/s41467-026-70729-0

Figure Lengend Snippet: A Cytokines stimulated Slco4c1 mRNA transcription in primary mouse hepatocytes ( B ) FGF21 expression levels in different hepatic cell types. C Hepatic Fgf21 mRNA levels in GAN diet fed mice. D Correlation analysis between hepatic Fgf21 and Slco4c1 mRNA levels ( n = 6). E , F Treatment with FGF21 stimulated Slco4c1 mRNA and protein expression in primary mouse hepatocytes ( G ) Schematic illustration of the predicted transcription factors. H The predicted transcription factor mRNA transcripts in the FGF21-treated primary mouse hepatocytes. I , J Hepatic Egr1/2/3 mRNA transcripts and protein expression in the indicated groups of mice. (* p < 0.05, vs. Chow diet-WT) ( K ) Correlation between hepatic Slco4c1 and Egrs mRNA levels in the GAN diet-fed WT mice ( n = 6). L A diagram illustrating the potential EGRs binding sites in human SLCO4C1 proximal promoter and the reporter constructs. M Luciferase activities in 293 T cells co-transfected with truncated SLCO4C1 promoters with, or without, plasmids for EGRs overexpression. N A schematic diagram displayed the EGR1-binding site in the SLCO4C1 promoter and its mutant. O Luciferase activity in 293 T cells co-transfected with the mutant Slco4c1 promoter and the plasmid for EGR1 overexpression. Relative levels of Egr1 mRNA ( P ) and protein ( Q ) expression in primary mouse hepatocytes treated with, or without, an ERK/MAPK inhibitor, and after stimulated by FGF21 were examined. R ChIP assay revealed that FGF21 increased Egr1 binding to the Slco4c1 -59 promoters in primary mouse hepatocytes. Relative levels Slco4c1 mRNA (S) and protein (T) expression in primary mouse hepatocytes treated with, or without, an ERK/MAPK inhibitor, and after stimulated by FGF21 were examined. A n = 5 and M , O n = 3, Biological replicates; C , I , J Each dot represents one mouse sample; Statistics: unpaired two-tailed Student’s t test. R: n = 3 and E , F , H , P , Q , S , T n = 5, Biological replicates; Statistics: one-way ANOVA test, Multiple comparisons. *p < 0.05, * *p < 0.01, *** p < 0.001, **** p < 0.0001. F: * p < 0.05 vs. FGF21 0 μg/ml; # p < 0.05 vs. FGF21 0.1 μg/ml. Q, T: * p < 0.05 vs. FGF21 0 μg/ml; # p < 0.05 vs. FGF21 1 μg/ml. All data statistics are presented as mean ± SD and 95% confidence interval.

Article Snippet: After fasting for 12 h, HepG2 cells were treated with 375 μM PA (MCE, New Jersey, USA, Cat: HY-N0830) in a complete medium for 12 h or 24 h. The isolated primary mouse hepatocytes were cultured in 5% fetal bovine serum-Williams’ Medium E for 6-8 h, and subsequently treated with 250 μM PA for 12 h or 24 h. In addition, the cells were treated with different concentrations of FGF21 (SinoBiological, Beijing, China, Cat:10911-HNAE) for varying time periods and their viability was examined by CCK-8 assays using the specific kit (Bgbiotech, Chongqing, China, Cat: L2544823X).

Techniques: Expressing, Binding Assay, Construct, Luciferase, Transfection, Over Expression, Mutagenesis, Activity Assay, Plasmid Preparation, Two Tailed Test

Journal: Nature Communications

Article Title: Hepatocyte SLCO4C1 is a cAMP uptake transporter for inhibiting lipogenesis and a therapeutic target for MASLD

doi: 10.1038/s41467-026-70729-0

Figure Lengend Snippet: During the pathogenic process, metabolic disorder stimulates FGF21 expression, which through its receptors, activates the ERK/MAPK signaling to induce EGR1 expression. The transcription factor of EGR1 binds to the SLCO4C1 promoter and up-regulates its expression in hepatocytes. The SLCO4C1 functions as a cAMP uptake transporter through the interaction of its Gln463 with cAMP, increasing intracellular cAMP levels that activate the PKA-CREB signaling to feedback down-regulate SREBP1 and downstream ACC1, FASN and SCD1 expression, inhibiting fatty acid synthesis. Accordingly, induction of SLCO4C1 overexpression by AAV8-mediated hepatic SLCO4C1 expression and/or increasing intracellular cAMP levels by the Forskolin treatment effectively prevent and mitigate the progression of MASLD. Therefore, SLCO4C1 is a therapeutic target for MASLD. Conceivably, our findings may aid in the design of therapeutic strategies for treating MASLD.

Article Snippet: After fasting for 12 h, HepG2 cells were treated with 375 μM PA (MCE, New Jersey, USA, Cat: HY-N0830) in a complete medium for 12 h or 24 h. The isolated primary mouse hepatocytes were cultured in 5% fetal bovine serum-Williams’ Medium E for 6-8 h, and subsequently treated with 250 μM PA for 12 h or 24 h. In addition, the cells were treated with different concentrations of FGF21 (SinoBiological, Beijing, China, Cat:10911-HNAE) for varying time periods and their viability was examined by CCK-8 assays using the specific kit (Bgbiotech, Chongqing, China, Cat: L2544823X).

Techniques: Expressing, Over Expression

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: Mouse FGF21 protein levels in each plasma sample were determined using a Mouse/Rat FGF‐21 Quantikine ELISA Kit (R&D Systems) according to the manufacturer's instructions.

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: Mouse FGF21 protein levels in each plasma sample were determined using a Mouse/Rat FGF‐21 Quantikine ELISA Kit (R&D Systems) according to the manufacturer's instructions.

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: Mouse FGF21 protein levels in each plasma sample were determined using a Mouse/Rat FGF‐21 Quantikine ELISA Kit (R&D Systems) according to the manufacturer's instructions.

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: Mouse FGF21 protein levels in each plasma sample were determined using a Mouse/Rat FGF‐21 Quantikine ELISA Kit (R&D Systems) according to the manufacturer's instructions.

Techniques: Concentration Assay