Journal: Cell Stem Cell

Article Title: Generation of human appetite-regulating neurons and tanycytes from pluripotent stem cells

doi: 10.1016/j.stem.2026.05.005

Figure Lengend Snippet: In vitro -derived tanycytes map to the b2 subtype and respond to FGF1 (A–C) (A) Integration of day 16 data with “tanycytes” cluster from days 25 and 50 + 70 datasets, (B) annotated clusters, and (C) pseudotime trajectory (monocle 3), (1) indicates trajectory root. (D) Gene expression dynamics of selected markers of dotted outline from (C) along pseudotime. (E) Feature plots of key tanycyte markers. (F) Mapping spatial location of the days 50 + 70 tanycyte cluster onto spatial transcriptomic reference of human hypothalamus. (G) ICC on 2D ARC, scale bar: 25 μm. (H) ICC/ISH on xenografts, scale bars: 50 μm. (I) Volcano plot of DEG in tanycytes after 30min stimulation of 50 ng/mL FGF1 in days 50 + 70 cultures ( n = 3 each, RC17). Benjamini-Hochberg corrected p values. (J) DE of EGR1 and FOS across annotated cell types. Significant upregulation in tanycytes shown in red.

Article Snippet: FGF1 (recombinant human) , Miltenyi Biotec , Cat#130-095-789.

Techniques: In Vitro, Derivative Assay, Gene Expression

Journal: JHEP Reports

Article Title: FGF1 ameliorates hepatic steatosis through acute activation of the unfolded protein response and VLDL production

doi: 10.1016/j.jhepr.2025.101660

Figure Lengend Snippet: FGF1 reduces hepatic steatosis and acutely induces ApoB. (A) Hepatic TG in high-fat diet-fed adipose-specific Fgfr1 -/- mice treated with FGF1 every 3 days for 5 weeks (Mann-Whitney U test; ∗∗ p < 0.01). (B) Plasma free fatty acid levels, (C) plasma TG, and (D) total cholesterol levels 24 h after an FGF1 injection in chow-fed ob/ob mice (Mann-Whitney U test; ∗ p < 0.05). (E) Volcano plot of significantly (red) and non-significantly (green) affected plasma proteins in chow-fed ob/ob mice after 24 h FGF1 treatment as determined by untargeted proteomics. Arrow highlights ApoB. (F) Profiling of apolipoproteins in plasma of chow-fed ob/ob mice after 24 h of FGF1 treatment using a targeted proteomics strategy (Mann-Whitney U test; ∗∗ p < 0.01). All panels n = 6-8. TG, triglyceride.

Article Snippet: Mice were treated with vehicle (PBS), recombinant FGF1 (0.5 mg/kg, R&D Systems) or the FGF1 K133E variant (kind gift by Birgitte Andersen, Novo Nordisk, Bagsværd Denmark) by intraperitoneal (i.p.) injection.

Techniques: MANN-WHITNEY, Clinical Proteomics, Injection, Targeted Proteomics

Journal: JHEP Reports

Article Title: FGF1 ameliorates hepatic steatosis through acute activation of the unfolded protein response and VLDL production

doi: 10.1016/j.jhepr.2025.101660

Figure Lengend Snippet: FGF1 acutely and transiently stimulates VLDL production in ob/ob mice. (A) Temporal dynamics of plasma TG in ob/ob mice upon FGF1 injection (Mann-Whitney U test; ∗∗ p < 0.01). (B) TG levels in FPLC fractions from plasma of ob/ob mice, 24 h after FGF1 injection. Inset: ApoB in FPLC fractions 7, 9, 11 and 13 corresponding to VLDL. (C) Plasma TG/ApoB ratios 24 h after an FGF1 injection in ob/ob. (D) Left panel: plasma TG levels upon LPL inhibition by poloxamer in 14 h FGF1-stimulated ob/ob and right panel: calculated production rate from the curves. (E) Plasma TG in ob/ob mice 24 h after FGF1 K133E administration (Mann-Whitney U test; ∗∗ p < 0.01). All panels n = 6-8. FPLC, fast protein liquid chromatography; TG, triglyceride.

Article Snippet: Mice were treated with vehicle (PBS), recombinant FGF1 (0.5 mg/kg, R&D Systems) or the FGF1 K133E variant (kind gift by Birgitte Andersen, Novo Nordisk, Bagsværd Denmark) by intraperitoneal (i.p.) injection.

Techniques: Clinical Proteomics, Injection, MANN-WHITNEY, Inhibition, Fast Protein Liquid Chromatography

Journal: JHEP Reports

Article Title: FGF1 ameliorates hepatic steatosis through acute activation of the unfolded protein response and VLDL production

doi: 10.1016/j.jhepr.2025.101660

Figure Lengend Snippet: Anti-steatotic FGF1 effects are not associated with adipose lipolysis, hepatic lipogenesis or β-oxidation. (A) Fatty acid synthesis and elongation rates of most common fatty acids using 13 C-acetate in ob/ob mouse livers during 24 h of FGF1 treatment. (B) Hepatic levels of lipogenesis proteins ACC and FAS, as well as phosphorylation of ACC in ob/ob mice 14 h after FGF1 injection. (C) Hepatic long-chain (C14–C18) acylcarnitines and (D) plasma acylcarnitines of 14 h FGF1-treated ob/ob mice. (E) Respiratory exchange ratios of FGF1-treated (at arrow) ob/ob mice. Mann-Whitney U test; ∗ p < 0.05, ∗∗ p < 0.01; n = 6-8.

Article Snippet: Mice were treated with vehicle (PBS), recombinant FGF1 (0.5 mg/kg, R&D Systems) or the FGF1 K133E variant (kind gift by Birgitte Andersen, Novo Nordisk, Bagsværd Denmark) by intraperitoneal (i.p.) injection.

Techniques: Phospho-proteomics, Injection, Clinical Proteomics, MANN-WHITNEY

Journal: JHEP Reports

Article Title: FGF1 ameliorates hepatic steatosis through acute activation of the unfolded protein response and VLDL production

doi: 10.1016/j.jhepr.2025.101660

Figure Lengend Snippet: FGF1 hyperactivates the UPR in the liver and hepatocytes. (A) Hepatic protein levels of the three UPR branch markers XBP1s, ATF6 (ATF6-U: unspliced & ATF6-N nuclear) and Perk phosphorylation 14 h after FGF1 injection of ob/ob showing UPR activation. In addition, XBP1s and ATF6 in nuclear extracts from these livers. (B) Hepatic expression levels of UPR chaperones ( Grp78 , Erp72 , Erdj3 , Grp94 , and Pdi ), ER-associated protein degradation genes ( Edem and Herp ), and PERK–ATF4–CHOP pathway genes ( Chop and Gadd34 ) in ob/ob mouse liver (Mann-Whitney U test; ∗ p < 0.05, ∗∗ p < 0.01). (C) Hepatic protein levels of Grp78, Grp94, Erp72, Erp57, Pdi and Chop 14 h after FGF1 injection of ob/ob mice. (D) Effect of 3 or 6 h FGF1 on UPR sensors in glucosamine-stressed HepG2 cells, showing Xbp1 mRNA (uXBP1: unspliced & sXBP: spliced), Ire1 and Perk phosphorylation, XBP1s and Atf6 protein levels (unspliced & nuclear) (E) Hyperactivation of UPR chaperone expression levels but not ERAD genes by 6 h FGF1 treatment in glucosamine-stressed (2 h) primary rat hepatocytes. ∗ p < 0.05 glucosamine vs. control, # p < 0.05 glucosamine vs. glucosamine + FGF1 (Kruskal-Wallis test). (F) UPR chaperone protein induction after FGF1 treatment in HepG2 cells with and without glucosamine pre-treatment. UPR, unfolded protein response.

Article Snippet: Mice were treated with vehicle (PBS), recombinant FGF1 (0.5 mg/kg, R&D Systems) or the FGF1 K133E variant (kind gift by Birgitte Andersen, Novo Nordisk, Bagsværd Denmark) by intraperitoneal (i.p.) injection.

Techniques: Phospho-proteomics, Injection, Activation Assay, Expressing, MANN-WHITNEY, Control

Journal: JHEP Reports

Article Title: FGF1 ameliorates hepatic steatosis through acute activation of the unfolded protein response and VLDL production

doi: 10.1016/j.jhepr.2025.101660

Figure Lengend Snippet: FGF1 stimulates major regulators of protein synthesis that link to the UPR. (A) Temporal phosphorylation dynamics of signaling pathways in FGF1-stimulated HepG2 cells and primary rat hepatocytes: RSK, mTOR and downstream targets, 4E-BP1, P70S6K, eF2K and S6. (B) Phosphorylation of FRS2α, 4E-BP1, P70S6K, RSK, and S6 in livers of DIO mice 15 min after FGF1 stimulation. (C) Suppression of FGF1-induced UPR hyperactivation by inhibition of PI3K, mTOR, protein translation, ER protein import and a chemical protein folding chaperone in HepG2 cells (Kruskal-Wallis-test). ∗ p < 0.05 ER stress vs. ER stress + FGF1, # p < 0.05 ER stress + FGF1 vs. ER stress + FGF1 + inhibitor. DIO, diet-induced obese; ER, endoplasmic reticulum; UPR, unfolded protein response.

Article Snippet: Mice were treated with vehicle (PBS), recombinant FGF1 (0.5 mg/kg, R&D Systems) or the FGF1 K133E variant (kind gift by Birgitte Andersen, Novo Nordisk, Bagsværd Denmark) by intraperitoneal (i.p.) injection.

Techniques: Phospho-proteomics, Protein-Protein interactions, Inhibition

Journal: JHEP Reports

Article Title: FGF1 ameliorates hepatic steatosis through acute activation of the unfolded protein response and VLDL production

doi: 10.1016/j.jhepr.2025.101660

Figure Lengend Snippet: FGF1-induced hepatic TG clearance requires pre-existing ER stress. Temporal dynamics of plasma TG upon an FGF1 injection in (A) wild-type mice, (B) wild-type mice pre-treated with tunicamycin (Mann-Whitney U test; ∗ p < 0.05, ∗∗ p < 0.01). (C) Plasma ALT levels after tunicamycin pre-treatment showing no liver damage and (D) after 3-days of phenylbutyrate pre-treatment in DIO mice showing ER liver damage reduction (Mann-Whitney U test; ∗∗∗ p < 0.001). (E) Temporal dynamics of plasma TG upon an FGF1 injection in DIO mice with or without pre-treatment for 3 days with the ER chaperone phenylbutyrate (Kruskal-Wallis-test; ∗∗∗ p < 0.001 FGF1 vs. PBS, ### p < 0.001 FGF1 vs. PHB, $ p < 0.05 FGF1 vs. PHB+FGF1). (F) Albumin levels in ob/ob and wild-type mice 24 h after FGF1 injection (Mann-Whitney U test; ∗∗∗ p < 0.01). (G) Temporal dynamics of plasma ALT in ob/ob mice after a single FGF1 injection showing a transient reduction in liver damage (Mann-Whitney U test; ∗ p < 0.05, ∗∗ p < 0.01). (H) Model summarizing the underlying mechanism of FGF1-induced clearance of hepatic steatosis; in blue, the elements of the signaling pathways and UPR that are affected downstream of FGF1 binding and the subsequent secretory output. n = 5-6, n = 11 for panel E. ∗ p < 0.05, ∗∗ p < 0.01. ALT, alanine aminotransferase; DIO, diet-induced obese; ER, endoplasmic reticulum; TG, triglyceride; UPR, unfolded protein response.

Article Snippet: Mice were treated with vehicle (PBS), recombinant FGF1 (0.5 mg/kg, R&D Systems) or the FGF1 K133E variant (kind gift by Birgitte Andersen, Novo Nordisk, Bagsværd Denmark) by intraperitoneal (i.p.) injection.

Techniques: Clinical Proteomics, Injection, MANN-WHITNEY, Protein-Protein interactions, Binding Assay