LPIN1 promotes triglycerides synthesis and is transcriptionally regulated by PPARG in buffalo mammary epithelial cells

Zhou, Fangting; Fan, Xinyang; Miao, Yongwang

doi:10.1038/s41598-022-06114-w

Cited by 16 publications

(15 citation statements)

References 34 publications

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“…lpin1 deficiency in fatty liver dystrophy ( fld ) mutant mice causes male infertility and impairment of adipose tissue development [ 25 ]. The overexpression of lpin1 leads to the accumulation of triacylglycerol (TAG), which is the final product of PA [ 26 , 27 , 28 ]. To investigate lipid accumulation in dKO mice, frozen sections were obtained from the testes of WT and dKO mice and stained with Oil Red O to visualize lipid droplets (LDs) containing TAG in the cytoplasm.…”

Section: Resultsmentioning

confidence: 99%

Proteasome-Associated Proteins, PA200 and ECPAS, Are Essential for Murine Spermatogenesis

et al. 2023

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Proteasomes are highly sophisticated protease complexes that degrade non-lysosomal proteins, and their proper regulation ensures various biological functions such as spermatogenesis. The proteasome-associated proteins, PA200 and ECPAS, are predicted to function during spermatogenesis; however, male mice lacking each of these genes sustain fertility, raising the possibility that these proteins complement each other. To address this issue, we explored these possible roles during spermatogenesis by producing mice lacking these genes (double-knockout mice; dKO mice). Expression patterns and quantities were similar throughout spermatogenesis in the testes. In epididymal sperm, PA200 and ECPAS were expressed but were differentially localized to the midpiece and acrosome, respectively. Proteasome activity was considerably reduced in both the testes and epididymides of dKO male mice, resulting in infertility. Mass spectrometric analysis revealed LPIN1 as a target protein for PA200 and ECPAS, which was confirmed via immunoblotting and immunostaining. Furthermore, ultrastructural and microscopic analyses demonstrated that the dKO sperm displayed disorganization of the mitochondrial sheath. Our results indicate that PA200 and ECPAS work cooperatively during spermatogenesis and are essential for male fertility.

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Section: Resultsmentioning

confidence: 99%

Proteasome-Associated Proteins, PA200 and ECPAS, Are Essential for Murine Spermatogenesis

et al. 2023

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“…GPAT4 and LPIN1 have been identified as important regulatory factors of lipid deposition through the glycerophospholipid metabolic pathway [ 17 ]. Interference with LPIN1 inhibited adipose tissue development and significantly reduced adipose tissue quality, whereas overexpression of LPIN1 in skeletal muscle or adipose tissue promoted obesity in mice [ 18 ].…”

Section: Discussionmentioning

confidence: 99%

Overexpression of DGAT2 Regulates the Differentiation of Bovine Preadipocytes

Guo

Jin

Zhang

et al. 2023

Animals

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Triacylglycerols (TAGs) are a major component of intramuscular fat. Diacylglycerol O-acyltransferase 2(DGAT2) expression determines the rate of TAG synthesis. The purpose of this study was to investigate the role of DGAT2 in the differentiation of Yanbian cattle preadipocytes and lipid metabolism-related signalling pathways. Bovine preadipocytes were infected with overexpression and interfering adenovirus vectors of DGAT2. The effects on the differentiation of Yanbian cattle preadipocytes were examined using molecular and transcriptomic techniques, including differentially expressed genes (DEGs) and Kyoto Encyclopaedia of Genes and Genomes (KEGG) pathway analysis. DGAT2 overexpression significantly increased (p < 0.05) intracellular TAG, adiponectin, and lipid droplet (LD) contents. Moreover, it upregulated (p < 0.05) peroxisome proliferator-activated receptor γ (PPARγ), CCAAT/enhancer binding protein α, and fatty acid binding protein 4 mRNA expression. In contrast, DGAT2 knockdown reduced intracellular TAG and LD content and downregulated (p < 0.05) C/EBPβ, mannosyl (alpha-1,3-)-glycoproteinbeta-1,2-N-acetylglucosaminyltransferase, lipin 1,1-acylglycerol-3-phosphate O-acyltransferase 4, and acetyl-CoA carboxylase alpha mRNA expression. Between DGAT2-overexpressing preadipocytes and normal cells, 208 DEGs were identified, including 106 upregulated and 102 downregulated genes. KEGG pathway analysis revealed DEGs mainly enriched in PPAR signalling and AMP-activated protein kinase pathways, cholesterol metabolism, and fatty acid biosynthesis. These results demonstrated that DGAT2 regulated preadipocyte differentiation and LD and TAG accumulation by mediating the expression of adipose differentiation-, lipid metabolism-, and fatty acid synthesis-related genes.

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“…As a known transcription factor, PPARγ can regulate the expression of ACS, FABP3, FABP4, and others [ 31 ]. The upregulated DEGs GPAT4, GPAM, and LPIN1 in the glycerophospholipid metabolic pathway have been identified as important regulators of lipid deposition [ 32 , 33 ]. AMPK signaling plays a crucial role in systemic metabolic pathways by regulating energy homeostasis and cellular lipid metabolism [ 34 , 35 , 36 ].…”

Section: Discussionmentioning

confidence: 99%

Overexpression of DGAT2 Stimulates Lipid Droplet Formation and Triacylglycerol Accumulation in Bovine Satellite Cells

Zhang

et al. 2022

Animals

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Intramuscular fat (IMF) is closely related to the tenderness, juiciness, and flavor of beef, and is an important indicator for beef quality assessment internationally. The main components of skeletal intramuscular fat (IMF) are phospholipids and triacylglycerols (TAG), and the final step of TAG biosynthesis is catalyzed by diacylglycerol acyltransferase 2 (DGAT2). To explore the effect of DGAT2 on the differentiation of bovine muscle satellite cells (BSCs) and its role in the signaling pathway related to lipid metabolism, the adenovirus overexpression and interference vector of the DGAT2 gene was constructed in this study, and the overexpression adenovirus Ad-DGAT2 and interfering adenovirus sh-DGAT2 were used to infect BSCs. Overexpression of DGAT2 resulted in a significant increase in the contents of TAG and ADP, and the mRNA and protein expression levels of PPARγ, C/EBPα, and SREBF1 (p < 0.05). Interfering with the expression of DGAT2 reduced the intracellular TAG content and lipid droplet accumulation. Furthermore, the mRNA and protein expression levels of PPARγ, C/EBPα, and SREBF1 (p < 0.05) were significantly downregulated. Transcriptome sequencing showed that a total of 598 differentially expressed genes (DEGs) were screened in BSCs infected with Ad-DGAT2, and these DEGs included 292 upregulated genes and 306 downregulated genes. A total of 49 DEGs were screened in BSCs infected with sh-DGAT2, and these DEGs included 25 upregulated and 24 downregulated genes. KEGG enrichment analysis showed that the DEGs, after overexpression of DGAT2, were mainly enriched in the PPAR signaling pathway, and the fat digestion and absorption, glycerophospholipid metabolism, fatty acid biosynthesis, and AMPK signaling pathways. The DEGs obtained after interfering with DGAT2 were mainly enriched in the metabolic pathways, such as the PPAR signaling pathway and PI3K/AKT signaling pathway. In summary, our study demonstrated that the lipid droplet formation, TAG accumulation, and adipogenic gene expression in BSCs overexpressing DGAT2 were higher than those in the control cells. These results highlight the important role of DGAT2 in regulating BSCs during adipogenic transdifferentiation and underscore the complexity of intramuscular adipogenesis.

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LPIN1 promotes triglycerides synthesis and is transcriptionally regulated by PPARG in buffalo mammary epithelial cells

Cited by 16 publications

References 34 publications

Proteasome-Associated Proteins, PA200 and ECPAS, Are Essential for Murine Spermatogenesis

Proteasome-Associated Proteins, PA200 and ECPAS, Are Essential for Murine Spermatogenesis

Overexpression of DGAT2 Regulates the Differentiation of Bovine Preadipocytes

Overexpression of DGAT2 Stimulates Lipid Droplet Formation and Triacylglycerol Accumulation in Bovine Satellite Cells

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