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November 8, 2022Frontiers in ImmunologyOpen Access

ApoA4 deficiency in mice fed a high-fat diet led to significant increases in inflammatory macrophages and activated granulocytes, promoting the development of nonalcoholic fatty liver.

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Why the study?

Does ApoA4 deficiency alter the liver immune microenvironment and exacerbate nonalcoholic fatty liver in a mouse model?

Population

Five-week-old male C57BL/6 wild type mice and ApoA4 knockout mice fed a high-fat diet for 16 weeks to…

Comparison

ApoA4 gene knockout and in vivo ApoA4… vs Wild-type (WT) mice and AAV-GFP injected KO mice.

Design

Preclinical

Follow-up

16 weeks

Key result

ApoA4 deficiency in mice fed a high-fat diet led to significant increases in inflammatory macrophages and activated granulocytes, promoting the development of nonalcoholic fatty liver.

Authors

XLXiaohuan LiuJZJinting ZhouCYChunxia Yan

Discussion

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Overview

ApoA4 effects on hepatic immune cells in NAFL models warrant human validation; leaves open therapeutic targeting in patients.

Structured PICO

Does ApoA4 deficiency alter the liver immune microenvironment and exacerbate nonalcoholic fatty liver in a mouse model?

P
Population
6 male C57BL/6 wild type and ApoA4 knockout mice fed a high-fat diet for 16 weeks to establish a NAFL model.
E
Exposure
ApoA4 gene knockout (deficiency) and in vivo ApoA4 overexpression via AAV-ApoA4-GFP injection.
C
Comparator
Wild-type (WT) mice and AAV-GFP injected KO mice.
O
Outcome
Reprogramming of liver immune cells, specifically the abundance of immune subsets and gene expression profiles assessed by scRNA-seq.surrogate

ApoA4 deficiency exacerbates nonalcoholic fatty liver by reprogramming the liver immune microenvironment, specifically increasing inflammatory macrophages and activated granulocytes.

Limitations

  • Insufficient investigation limits interpretation of how adaptive immune cells are regulated by ApoA4 in NAFL.
  • Cellular crosstalk between immune cells needs to be further explored.
  • It remains to be determined whether the near disappearance of some kind of granulocytes after ApoA4 deficiency are pathogenic factors linked to NAFL progression.
  • Technical limitations and heterogeneity of algorithms for scRNA-seq data analyses.

Cite This Study

Liu et al. (2022) studied Nonalcoholic fatty liver (NAFL) (n=6). ApoA4 deficiency vs. Wild type was evaluated on Hepatic immune cell populations and gene expression profiles. ApoA4 deficiency in mice fed a high-fat diet led to significant increases in inflammatory macrophages and activated granulocytes, promoting the development of nonalcoholic fatty liver.

synapsesocial.com/papers/6aab8d1bbbaa9ba62dcc689chttps://doi.org/10.3389/fimmu.2022.1038401
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