Key Factors Governing Initial Stages of Lipid Droplet Formation

Background/Aims: An increase in intracellular lipid droplet formation and hepatic triglyceride (TG) content usually results in nonalcoholic fatty liver disease. However, the mechanisms underlying the regulation of hepatic TG homeostasis remain unclear. Methods: Oil red O staining and TG measurement were performed to determine the lipid content. miRNA expression was evaluated by quantitative PCR. A luciferase assay was performed to validate the regulation of Yin Yang 1 (YY1) by microRNA (miR)-122. The effects of miR-122 expression on YY1 and its mechanisms involving the farnesoid X receptor and small heterodimer partner (FXR-SHP) pathway were evaluated by quantitative PCR and Western blot analyses. Results: miR-122 was downregulated in free fatty acid (FFA)-induced steatotic hepatocytes, and streptozotocin and high-fat diet (STZ-HFD) induced nonalcoholic steatohepatitis (NASH) in mice. Transfection of hepatocytes with miR-122 mimics before FFA induction inhibited lipid droplet formation and TG accumulation in vitro. These results were verified by overexpressing miR-122 in the livers of STZ-HFD-induced NASH mice. The 3’-untranslated region (3’UTR) of YY1 mRNA is predicted to contain an evolutionarily conserved miR-122 binding site. In silico searches, a luciferase reporter assay and quantitative PCR analysis confirmed that miR-122 directly bound to the YY1 3’UTR to negatively regulate YY1 mRNA in HepG2 and Huh7 cells. The (FXR-SHP) signaling axis, which is downstream of YY1, may play a key role in the mechanism of miR-122-regulated lipid homeostasis. YY1-FXR-SHP signaling, which is negatively regulated by FFA, was enhanced by miR-122 overexpression. This finding was also confirmed by overexpression of miR-122 in the livers of NASH mice. Conclusions: The present results indicate that miR-122 plays an important role in lipid (particularly TG) accumulation in the liver by reducing YY1 mRNA stability to upregulate FXR-SHP signaling.

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Four-and-a-half LIM-domain protein affects diet induced (hepatic) steatosis and lipid droplet formation

Journal of Hepatology ◽

10.1016/s0168-8278(18)30918-8 ◽

2018 ◽

Vol 68 ◽

pp. S348

Author(s):

J. Sommer ◽

C. Hellerbrand

Keyword(s):

Hepatic Steatosis ◽

Lipid Droplet ◽

Droplet Formation ◽

Lim Domain ◽

Lipid Droplet Formation ◽

Lim Domain Protein ◽

Domain Protein

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Classical Activation of Macrophages Leads to Lipid Droplet Formation Without de novo Fatty Acid Synthesis

Frontiers in Immunology ◽

10.3389/fimmu.2020.00131 ◽

2020 ◽

Vol 11 ◽

Cited By ~ 9

Author(s):

Mauricio Rosas-Ballina ◽

Xue Li Guan ◽

Alexander Schmidt ◽

Dirk Bumann

Keyword(s):

Fatty Acid ◽

Lipid Droplet ◽

Fatty Acid Synthesis ◽

De Novo ◽

Acid Synthesis ◽

Droplet Formation ◽

Classical Activation ◽

Lipid Droplet Formation

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Perilipin1 promotes unilocular lipid droplet formation through the activation of Fsp27 in adipocytes

Nature Communications ◽

10.1038/ncomms2581 ◽

2013 ◽

Vol 4 (1) ◽

Cited By ~ 127

Author(s):

Zhiqi Sun ◽

Jingyi Gong ◽

Han Wu ◽

Wenyi Xu ◽

Lizhen Wu ◽

...

Keyword(s):

Lipid Droplet ◽

Droplet Formation ◽

Lipid Droplet Formation

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Characterisation of gene expression related to milk fat synthesis in the mammary tissue of lactating yaks

Journal of Dairy Research ◽

10.1017/s0022029917000413 ◽

2017 ◽

Vol 84 (3) ◽

pp. 283-288 ◽

Cited By ~ 9

Author(s):

Jung Nam Lee ◽

Yong Wang ◽

Ya Ou Xu ◽

Yu Can Li ◽

Fang Tian ◽

...

Keyword(s):

Gene Expression ◽

Dairy Cows ◽

Lipid Droplet ◽

Milk Fat ◽

De Novo ◽

Droplet Formation ◽

Synthesis Process ◽

Lipid Droplet Formation ◽

Fat Synthesis ◽

Milk Fat Synthesis

This research communication describes the profile of gene expression related to the synthesis of yak milk as determined via quantitative reverse transcription polymerase chain reaction (RT-qPCR). Significant up-regulation during lactation were observed in genes related to fatty acid (FA) uptake from blood (LPL, CD36), intracellular FA transport (FABP3), intracellular FA activation of long- and short-chain FAs (ACSS1, ACSS2, ACSL1), de novo synthesis (ACACA), desaturation (SCD), triacyglycerol (TAG) synthesis (AGPAT6, GPAM, LPIN1), lipid droplet formation (PLIN2, BTN1A1, XDH), ketone body utilisation (BDH1, OXCT1), and transcription regulation (THRSP, PPARGC1A). In particular, intracellular de novo FA synthesis (ACSS2, ACACA, and FABP3) and TAG synthesis (GPAM, AGPAT6, and LPIN1), whose regulation might be orchestrated as part of the gene network under the control of SERBF1 in the milk fat synthesis process, were more activated compared to levels in dairy cows. However, the genes involved in lipid droplet formation (PLIN2, XDH, and BTN1A1) were expressed at lower levels compared to those in dairy cows, where these genes are mainly controlled by the PPARG regulator.

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