SEARCHOTHERpreclinical research, biomedical research

other·preclinical research, biomedical research, animal science, agriculture, nutrition·PMC10299640

Hif1α/Dhrs3a Pathway Participates in Lipid Droplet Accumulation via Retinol and Ppar-γ in Fish Hepatocytes

International Journal of Molecular Sciences · 13 authors, 3 centres

AI SUMMARY

FIDELITY 100%

This summary was generated by AI from a single paper. It has not been reviewed by a clinician and is not clinical advice. Verify against the source before acting on it.

AGENT 01 · STRUCTURED SUMMARY

TRACE TO SOURCE

“

TL;DR

This in vitro study using a zebrafish liver cell line found that the Hif1α/Dhrs3a pathway promotes lipid droplet accumulation by increasing retinol, which activates the Ppar-γ signaling pathway.

Full summary

1,003 CHARS

Using the zebrafish liver cell line (ZFL), this preclinical study investigated mechanisms of hepatic lipid droplet (LD) accumulation relevant to fatty liver in cultured fish. Incubation with fatty acids induced LD accumulation and differential expression of LD-related genes, including *dhrs3a*. RNAi knockdown of *dhrs3a* delayed LD accumulation and decreased *pparg* expression. Dhrs3 catalyzed the conversion of retinal to retinol, which increased in LD-enriched cells. Exogenous retinyl acetate maintained LD accumulation only in a lipid-rich medium, increased *pparg* expression, and altered lipid composition (increasing phosphatidylcholine and triacylglycerol; decreasing cardiolipin, phosphatidylinositol, and phosphatidylserine). Inhibition of HIF1α with LW6 reduced LD size/number and attenuated mRNA levels of *hif1αa*, *hif1αb*, *dhrs3a*, and *pparg*. The study proposes a pathway where Hif1α regulates *dhrs3a*, leading to retinol formation and Ppar-γ activation, promoting LD accumulation.

STUDY TYPE

other

SPECIALTY

preclinical research

SUMMARISED BY

AI pipeline

FIDELITY CHECK

100% · A

ORIGINAL PAPER

PMC10299640

Hif1α/Dhrs3a Pathway Participates in Lipid Droplet Accumulation via Retinol and Ppar-γ in Fish Hepatocytes

International Journal of Molecular Sciences

READ THE FULL PAPER

ABSTRACT

Excessive hepatic lipid accumulation is a common phenomenon in cultured fish; however, its underlying mechanisms are poorly understood. Lipid droplet (LD)-related proteins play vital roles in LD accumulation. Herein, using a zebrafish liver cell line (ZFL), we show that LD accumulation is accompanied by differential expression of seven LD-annotated genes, among which the expression of dehydrogenase / reductase ( SDR family ) member 3 a / b ( dhrs3a / b ) increased synchronously. RNAi-mediated knockdown of dhrs3a delayed LD accumulation and downregulated the mRNA expression of peroxisome proliferator-activated receptor gamma ( pparg ) in cells incubated with fatty acids. Notably, Dhrs3 catalyzed retinene to retinol, the content of which increased in LD-enriched cells. The addition of exogenous retinyl acetate maintained LD accumulation only in cells incubated in a lipid-rich medium. Correspondingly, exogenous retinyl acetate significantly increased pparg mRNA expression levels and altered the lipidome of the cells by increasing the phosphatidylcholine and triacylglycerol contents and decreasing the cardiolipin, phosphatidylinositol, and phosphatidylserine contents. Administration of LW6, an hypoxia-inducible factor 1α (HIF1α) inhibitor, reduced the size and number of LDs in ZFL cells and attenuated hif1αa , hif1αb , dhrs3a , and pparg mRNA expression levels. We propose that the Hif-1α/Dhrs3a pathway participates in LD accumulation in hepatocytes, which induces retinol formation and the Ppar-γ pathway.

CITATION EXPORT

Jingjing Tian, Yihui Du, Binbin Wang et al.. Hif1α/Dhrs3a Pathway Participates in Lipid Droplet Accumulation via Retinol and Ppar-γ in Fish Hepatocytes. International Journal of Molecular Sciences. (2023). https://doi.org/10.3390/ijms241210236

AUTHORS

13 · 3 CENTRES

Jingjing Tian, Yihui Du, Binbin Wang, Mengmeng Ji, Hongyan Li, Yun Xia, Kai Zhang, Zhifei Li, Wenping Xie, Wangbao Gong, Ermeng Yu, Guangjun Wang, Jun Xie

1Key Laboratory of Aquatic Animal Immune Technology of Guangdong Province, Pearl River Fisheries Research Institute, Chinese Academy of Fishery Sciences, Guangzhou 510380, China; [email protected] (Y.D.); [email protected] (B.W.); [email protected] (M.J.); [email protected] (H.L.); [email protected] (Y.X.); [email protected] (K.Z.); [email protected] (Z.L.); [email protected] (W.X.); [email protected] (W.G.); [email protected] (E.Y.); [email protected] (G.W.)
2Key Laboratory of Tropical and Subtropical Fishery Resource Application and Cultivation, Pearl River Fisheries Research Institute, Chinese Academy of Fishery Sciences, Guangzhou 510380, China
3Hainan Fisheries Innovation Research Institute, Chinese Academy of Fishery Sciences, Sanya 572024, China

EDITOR / REVIEWER

Walter Wahli