ASGR1 is a promising target for lipid reduction in pigs with PON2 as its inhibitor.

Yunjun Yin, Jun Liu, Jia Yu, Dingcai Dong, Fei Gao, Libao Yu, Xuguang Du, Sen Wu

Abstract read

In one paragraph

Article in iScience, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it

0cells of the map it votes in

0citing papers in PubMed

–field-weighted citation impact

1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

8 authors.

Yunjun YinState Key Laboratory of Animal Biotech Breeding, College of Biological Sciences, China Agricultural University, Beijing 100193, China.

Jun LiuState Key Laboratory of Animal Biotech Breeding, College of Biological Sciences, China Agricultural University, Beijing 100193, China.

Jia YuState Key Laboratory of Animal Biotech Breeding, College of Biological Sciences, China Agricultural University, Beijing 100193, China.

Dingcai DongState Key Laboratory of Animal Biotech Breeding, College of Biological Sciences, China Agricultural University, Beijing 100193, China.

Fei GaoState Key Laboratory of Animal Biotech Breeding, College of Biological Sciences, China Agricultural University, Beijing 100193, China.

Libao YuThe Eighth Medical Center of PLA General Hospital, Beijing 100094, China.

Xuguang DuState Key Laboratory of Animal Biotech Breeding, College of Biological Sciences, China Agricultural University, Beijing 100193, China.

Sen WuState Key Laboratory of Animal Biotech Breeding, College of Biological Sciences, China Agricultural University, Beijing 100193, China.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Although the role of asialoglycoprotein receptor 1 (ASGR1) in lowering lipid levels is well established, recent studies indicate that ASGR1 inhibition can cause unexpected liver damage in pigs, raising a serious issue about whether ASGR1 can be a good target for treating ASCVD. Here, we utilized the CRISPR-Cas9 system to regenerate ASGR1-knockout pigs, who displayed decreased lipid profiles without observable liver damage. This was confirmed by the lower levels of serum ALT and AST, reduced expression of inflammation markers, and normal histological morphology. Also, we implemented immunoprecipitation combined with mass spectrometry (IP-MS) and discovered that paraoxonase-2 (PON2) can interact with and significantly degrade ASGR1 in a dose-dependent manner. This degradation reduced lipid levels in mice, accompanied by little inflammation. Our study highlights the effectiveness and safety of degrading ASGR1 to reduce lipid levels in pigs and provides a potential inhibitor of ASGR1.

Indexed as

GeneticsHuman metabolism

Identifiers

PMID39055948

DOI10.1016/j.isci.2024.110288

PMCPMC11269292

What Socratic holds

Textmetadata

LicenceCC BY

Read underepoch 390

Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.