JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
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2025
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IF 6.2
Zixing Chen,Chi Ho Jacky Chau,Andrew Erickson,Huafang Ding,Shouhe Huang,Wen-Sen He,Hanyue Zhu,Zhen-Yu Chen
Phytosterols have long been used to prevent hypercholesterolemia-related diseases, although their effects on intestinal cholesterol metabolism remain elusive. This study applied comparative proteomics to investigate the effects of various sterols on proteomic changes in differentiated Caco-2 cells. A total of 206, 231, 180, and 197 differentially expressed proteins were identified following treatment with cholesterol, β-sitosterol, stigmasterol, and campesterol, respectively. Functional enrichment analysis revealed that phytosterols significantly altered the proteome of Caco-2 cells, though their effect on cholesterol transport protein expression was negligible. Notably, while phytosterols did not regulate the expression of acyl-CoA:cholesterol acyltransferase 2 (ACAT2), β-sitosterol and stigmasterol significantly lowered the level of cholesterol oleate in Caco-2 cells by 57.1 ± 0.8% and 51.4 ± 3.9%, respectively, demonstrating that they inhibited ACAT2-catalyzed cholesteryl esterification activity. In view of the fact that cholesterol needs to be converted to cholesteryl esters before incorporation into chylomicrons, it was concluded that phytosterols primarily reduce intestinal cholesterol absorption by inhibiting ACAT2 enzyme activity rather than its gene expression. This study provides new insights into the regulation of cholesterol homeostasis by phytosterols in the small intestine.
研究领域:
营养生物化学
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分子生物学
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细胞生物学
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脂质代谢
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药理学
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蛋白质组学
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DOI
PubMed
高影响因子
Food & Function
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2025
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IF 5.4
Dapeng Chen,Jiayi Li,Xinyu Li,Kexin Zhang,Shujie Zeng,Shenjun Zhang,Longyun Li,Yongjian Xiong
Hispidulin, a dietary flavonoid occurring naturally in brown algae, has attracted considerable interest owing to its functions in modulating inflammatory responses and neutralizing reactive oxygen species. This study examined the consequences of hispidulin in a model of chemically induced acute colitis. RNA sequencing (RNA-seq), 16s rRNA-seq, and non-targeted metabolome were conducted to determine the mechanisms underlying hispidulin-induced effects on colitis. The findings revealed that hispidulin exhibited significant therapeutic benefits against colitis. In addition, treatment with hispidulin led to a decrease in pro-inflammatory cytokine levels as well as serum FITC-dextran concentrations. RNA-seq analysis demonstrated a notable increase in colonic ACAT2 expression in mice with colitis following hispidulin treatment. Furthermore, hispidulin administration resulted in the upregulation of GPX4, a reduction in ROS levels, and inhibition of epithelial ferroptosis in mice with colitis. Both genetic inhibition of ACAT2 in vitro and AAV-mediated knockdown of ACAT2 in vivo substantially negated the effects of hispidulin on GPX4/GSH levels, ROS levels, and lipid hydroperoxide accumulation in both NCM460 cells and epithelial cells derived from DSS exposed murine models. 16s rRNA-seq results showed that hispidulin increased abundance of Lactobacillus, NK4A136_group, Oscillibacter, Peptococcus, Adlercreutzia and decreased abundance of Turicimonas in colitic mice. Non-targeted metabolome results showed that hispidulin facilitated the metabolism of galactose and promoted unsaturated fatty acid biosynthesis in colitic mice. In summary, hispidulin reduced the advancement of acute colitis in mice by lessening ACAT2-mediated ferroptosis in epithelial cells, as well as altering composition of gut microbiota.
研究领域:
营养科学
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胃肠病学
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分子生物学
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微生物学
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药理学
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生物信息学
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PubMed
高影响因子
JOURNAL OF DAIRY SCIENCE
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2023
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IF 3.5
Shendong Zhou,Mengru Chen,Meijuan Meng,Nana Ma,Wan Xie,Xiangzhen Shen,Zhixin Li,Guangjun Chang
ABSTRACT Ketosis is a metabolic disease that often occurs in dairy cows postpartum and results from disordered lipid metabolism. Acetyl-coenzyme A (CoA) acetyltransferase 2 ( ACAT2 ) is important for balancing cholesterol and triglyceride ( TG ) metabolism; however, its role in subclinical ketotic dairy cows is unclear. This study aimed to explore the potential correlation between ACAT2 and lipid metabolism disorders in subclinical ketotic cows through in vitro and in vivo experiments. In the in vivo experiment, liver tissue and blood samples were collected from healthy cows ( CON , n = 6, β-hydroxybutyric acid [ BHBA ] concentration < 1.0 mM) and subclinical ketotic cows (subclinical ketosis [ SCK] , n = 6, BHBA concentration = 1.2–3.0 mM) to explore the effect of ACAT2 on lipid metabolism disorders in SCK cows. For the in vitro experiment, bovine hepatocytes ( BHEC ) were used as the model. The effects of BHBA on ACAT2 and lipid metabolism were investigated via BHBA concentration gradient experiments. Subsequently, the relation between ACAT2 and lipid metabolism disorder was explored by transfection with siRNA of ACAT2. Transcriptomics showed an upregulation of differentially expression genes ( DEGs ) during lipid metabolism and significantly lower ACAT2 mRNA levels in the SCK group. Compared with the CON group in vivo, the SCK group showed significantly higher expression levels of peroxisome proliferator–activated receptor γ ( PPARγ ) and sterol regulator element binding protein 1c ( SREBP1c ) and significantly lower expression levels of peroxisome proliferator-activated receptor α ( PPARα ), carnitine palmitoyl-transferase 1A ( CPT1A ), sterol regulatory element binding transcription factor 2 ( SREBP2 ), and 3-hydroxy-3-methylglutaryl-CoA reductase ( HMGCR ). Moreover, the SCK group had a significantly higher liver TG content and significantly lower plasma total cholesterol ( TC ) and free cholesterol ( FC ) content. These results were indicative of TG and cholesterol metabolism disorders in the liver of dairy cows with SCK. Additionally, the SCK group showed an increased expression of Perilipin-2 ( PLIN2 ), decreased expression of apolipoprotein B ( APOB ), and decreased plasma concentration of very low-density lipoproteins ( VLDL ) and low-density lipoproteins-cholesterol ( LDL-C ) by downregulating ACAT2, which indicated an accumulation of TG in liver. I n vitro experiments showed that BHBA induced an increase in the TG content of BHEC, decreased content TC, increased expression of PPARγ and SREBP1c, and decreased expression of PPARα, CPT1A, SREBP2, and HMGCR. Additionally, BHBA increased the expression of PLIN2 in BHEC, decreased the expression and fluorescence intensity of ACAT2, and decreased the VLDL and LDL-C contents. Furthermore, silencing ACAT2 expression increased the TG content; decreased the TC, VLDL, and LDL-C contents; decreased the expression of HMGCR and SREBP2; and increased the expression of SREBP1c; but had no effect on the expression of PLIN2. These results suggest that ACAT2 downregulation in BHEC promotes TG accumulation and inhibits cholesterol synthesis, leading to TG and cholesterol metabolic disorders. In conclusion, ACAT2 downregulation in the SCK group inhibited cholesterol synthesis, increased TG synthesis, and reduced the contents of VLDL and LDL-C, eventually leading to disordered TG and cholesterol metabolism.
研究领域:
兽医学
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分子生物学
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生物化学
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动物生理学
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PubMed
高影响因子
Journal of Animal Science and Biotechnology
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2022
·Vol. 13
·期 1
·1-13
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IF 6.175
Zhou Xiaoge,Mo Zhaoyi,Li Yankun,Huang Liang,Yu Sihai,Ge Lan,Hu Yamei,Shi Shengjie,Zhang Lutong,Wang Liguang,Gao Lei,Yang Gongshe,Chu Guiyan
Background Oleic acid is an abundant free fatty acid present in livestock that are in a negative energy-balance state, and it may have detrimental effects on female reproduction and fertility. Oleic acid induces lipid accumulation in bovine granulosa cells, which leads to a foam cell-like morphology and reduced steroidogenesis. However, why oleic acid increases lipid accumulation but decreases steroidogenesis remains unclear. This study focused on oleic acid’s effects on lipid type and steroidogenesis. Results Oleic acid increased the lipid accumulation in a concentration-dependent manner and mainly increased the triglyceride level and decreased the cholesterol ester level. Oleic acid also led to a decline in estradiol and progesterone production in porcine granulosa cells in vitro. In addition, oleic acid up-regulated the expression of CD36 and diacylglycerol acyltransferase 2, but down-regulated the expression of 3-hydroxy-3-methylglutaryl-coenzyme A reductase, scavenger receptor class B member 1 and acetyl-Coenzyme A acetyltransferase 2, as well as steroidogenesis-related genes, including cytochrome P450 family 11 subfamily A member 1, cytochrome P450 family 19 subfamily A member 1 and 3 as well as steroidogenic acute regulatory protein at the mRNA and protein levels. An oleic acid-rich diet also enhanced the triglyceride levels and reduced the cholesterol levels in ovarian tissues of female mice, which resulted in lower estradiol levels than in control-fed mice. Compared with the control, decreases in estrus days and the numbers of antral follicles and corpora lutea, as well as an increase in the numbers of the atretic follicles, were found in the oleic acid-fed female mice. Conclusions Oleic acid changed the lipid type stored in lipid droplets of ovarian granulosa cells, and led to a decrease in steroidogenesis. These results improve our understanding of fertility decline in livestock that are in a negative energy-balance state.
研究领域:
生殖生物学
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内分泌学
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动物科学
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DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）