Dietary long chain fatty acids shape innate immune cell tone and modulate inflammatory responses in the lung
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ABSTRACT:
PROVIDER: PRJNA1265253 | ENA |
REPOSITORIES: ENA
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Project description:Excessive intake of saturated fatty acids (SFAs), which are prevalent in diets high in fried foods and red meat, poses a significant threat for hepatocellular carcinoma (HCC). Herein, we found via Mendelian randomization (MR) analysis that SFAs could be one of the factors leading to HCC. However, the role and associated mechanism of SFAs in HCC progression remain poorly understood. Palmitic acid (PA) is the most common type of SFA. We therefore chose PA as an example of SFAs for our study. We identified zinc finger DHHC-type palmitoyltransferase 12 (ZDHHC12) as a key protein involved in the promotion of HCC progression by PA, which was accomplished by maintaining the stability of the recognized HCC-promoting gene histone deacetylase 8 (HDAC8). Mechanistically, supplementation with PA led to the upregulation of ZDHHC12 expression via activation of the transcription factor SWI/SNF-related BAF chromatin remodeling complex subunit ATPase 4 (SMARCA4). ZDHHC12 mediated the palmitoylation of HDAC8 at cysteine 244, thereby preventing the lysosomal degradation of HDAC8, which promoted the progression of HCC. In conclusion, this study revealed that ZDHHC12 was a key protein in palmitic acid-mediated HCC progression and that targeting HDAC8 could inhibit this process. These findings offer a potential therapeutic strategy for HCC patients with a high intake of saturated fatty acids, especially palmitic acid.
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Project description:In a randomized controlled dietary intervention study, we compared a diet enriched in polyunsaturated fatty acids (PUFA) with a diet enriched in saturated fatty acids (SFA) for influence on abdominal subcutaneous adipose tissue gene expression. We studied young lean adults; 11 women and 25 men. There was no significant difference in age, BMI, or gene expression between the PUFA and SFA groups before the intervention. The intervention lasted for seven weeks. We calculated for each gene the absolute difference in gene expression after vs. before intervention (deltas), and compared the deltas between the PUFA and SFA group using SAM. 12 genes were significantly differentially regulated by the two diets with a FDR of 25%. These include metabolic and adipokine genes. In conclusion, dietary fatty acids have a modest influence on white adipose tissue gene expression.
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