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Figure 1 Under fed conditions, HFSCs undergo proper activation and hair follicles transition from telogen to anagen. In contrast, fasting triggers dermal adipocyte lipolysis, releasing FFAs into the surrounding niche to be utilized by HFSCs. This metabolic reprogramming induces apoptosis in HFSCs, inhibiting

Journal Article

Correction to: Hierarchical inhibition of mTORC1 by glucose starvation-triggered AXIN lysosomal translocation and by AMPK

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Life Metabolism, Volume 4, Issue 2, April 2025, loaf003, https://doi.org/10.1093/lifemeta/loaf003

Published: 12 February 2025

Journal Article

Calorie restriction plugs lithocholic bile acid into the lysosomal AMPK pathway

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Benoit Viollet

Life Metabolism, Volume 4, Issue 2, April 2025, loaf005, https://doi.org/10.1093/lifemeta/loaf005

Published: 11 February 2025

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CR causes increased production of the secondary bile acid LCA from the bact...

in Calorie restriction plugs lithocholic bile acid into the lysosomal AMPK pathway

Published: 11 February 2025

Figure 1 CR causes increased production of the secondary bile acid LCA from the bacterial dehydroxylation of the primary bile acid CDCA. LCA binds to the TULP3-sirtuin complex, stimulating deacetylation of the V1E1 subunit of the v-ATPase on K52, K99, and K191 residues, which in turn triggers the regulator-a

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DC646 exerts FXR antagonistic effects by interacting with coactivator via Q...

in Development of cyclopeptide inhibitors specifically disrupting FXR–coactivator interaction in the intestine as a novel therapeutic strategy for MASH

Published: 08 February 2025

Figure 3 DC646 exerts FXR antagonistic effects by interacting with coactivator via Q296 and K303. (a) Strategy of the AlphaScreen assay in (b) and (c). (b and c) Various concentrations of Ivermectin are incubated with His-hFXRα-LBD to obtain the EC 50 of Ivermectin in recruiting the peptides of SRC2-3 (b) o

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DC646 antagonizes FXR via a novel molecular mechanism. (a) Strategy of the ...

in Development of cyclopeptide inhibitors specifically disrupting FXR–coactivator interaction in the intestine as a novel therapeutic strategy for MASH

Published: 08 February 2025

Figure 4 DC646 antagonizes FXR via a novel molecular mechanism. (a) Strategy of the AlphaScreen assay in (b). (b) IC 50 of DC646 in recruiting the peptides of SRC2-3 under different adding orders of DC646, adding DC646 after CDCA, DC646 combined with CDCA, or CDCA after DC646, which have been incubated with

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DC646 attenuates the pathologies of MCD-induced MASH mice. (a) Strategy of ...

in Development of cyclopeptide inhibitors specifically disrupting FXR–coactivator interaction in the intestine as a novel therapeutic strategy for MASH

Published: 08 February 2025

Figure 5 DC646 attenuates the pathologies of MCD-induced MASH mice. (a) Strategy of animal experiments. (b and c) Relative mRNA levels of the intestinal (b) or hepatic (c) FXR signaling ( n = 5 in each group). (d) Strategy of animal experiments. Mice have been fed an MCS diet or an MCD diet to induce MASH f

Image

MASH-improving effect of DC646 depends on FXR. (a) Strategy of animal exper...

in Development of cyclopeptide inhibitors specifically disrupting FXR–coactivator interaction in the intestine as a novel therapeutic strategy for MASH

Published: 08 February 2025

Figure 6 MASH-improving effect of DC646 depends on FXR. (a) Strategy of animal experiments. Fxr -null mice have been fed with an MCD to induce MASH for 2 weeks, and been orally administered with DC646. (b) Relative mRNA expression of FXR target genes in the intestine ( n = 4–6 in each group, the Ct value o

Journal Article

EDITOR'S CHOICE

Development of cyclopeptide inhibitors specifically disrupting FXR–coactivator interaction in the intestine as a novel therapeutic strategy for MASH

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Yazhou Li and others

Life Metabolism, Volume 4, Issue 2, April 2025, loaf004, https://doi.org/10.1093/lifemeta/loaf004

Published: 08 February 2025

Supplementary data

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Discovery of cyclopeptide as FXR antagonist. (a) Structures of FXR-LBD comp...

in Development of cyclopeptide inhibitors specifically disrupting FXR–coactivator interaction in the intestine as a novel therapeutic strategy for MASH

Published: 08 February 2025

Figure 1 Discovery of cyclopeptide as FXR antagonist. (a) Structures of FXR-LBD complex with agonists (CDCA and GW4064), an antagonist (Ivermectin), and coactivator. The crystal structures (PDB codes: 3DCT, 4WVD, and 6HL1) were structurally aligned with respect to LBD. Agonists and antagonist are shown as st

Image

Cyclopeptide DC646 as a potent FXR antagonist. (a) The rational design of t...

in Development of cyclopeptide inhibitors specifically disrupting FXR–coactivator interaction in the intestine as a novel therapeutic strategy for MASH

Published: 08 February 2025

Figure 2 Cyclopeptide DC646 as a potent FXR antagonist. (a) The rational design of the target cyclopeptides DC645–DC649. (b) Relative luciferase activity of the transfected HEK293T cells treated with vehicle or tested cyclopeptides at 100 µmol/L in the presence of GW4064 ( n = 3 in each group). (c) Strategy

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Brain-body mitochondrial distribution patterns lack coherence and point to tissue-specific regulatory mechanisms

DHHC5 regulates lacteal function and intestinal lipid absorption by maintaining VEGFR2 localization in lipid rafts

Regulation of DNA translocation of chromatin remodeler enzyme Chd1 by exit DNA unwrapping

Optimized upstream analytical workflow for single-nucleus transcriptomics in main metabolic tissues

Liver ERα mediates sex differences in metabolic pattern changes in response to time-restricted feeding

Correction to: Soy peptide as an antidote to undernutrition

Transporters in vitamin uptake and cellular metabolism: impacts on health and disease

Dietary sulfur amino acid restriction improves metabolic health by reducing fat mass

Intermittent fasting promotes HFSC death to inhibit hair growth

Under fed conditions, HFSCs undergo proper activation and hair follicles tr...

Correction to: Hierarchical inhibition of mTORC1 by glucose starvation-triggered AXIN lysosomal translocation and by AMPK

Calorie restriction plugs lithocholic bile acid into the lysosomal AMPK pathway

CR causes increased production of the secondary bile acid LCA from the bact...

DC646 exerts FXR antagonistic effects by interacting with coactivator via Q...

DC646 antagonizes FXR via a novel molecular mechanism. (a) Strategy of the ...

DC646 attenuates the pathologies of MCD-induced MASH mice. (a) Strategy of ...

MASH-improving effect of DC646 depends on FXR. (a) Strategy of animal exper...

Development of cyclopeptide inhibitors specifically disrupting FXR–coactivator interaction in the intestine as a novel therapeutic strategy for MASH

Discovery of cyclopeptide as FXR antagonist. (a) Structures of FXR-LBD comp...

Cyclopeptide DC646 as a potent FXR antagonist. (a) The rational design of t...

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