JOURNAL OF NUTRITIONAL BIOCHEMISTRY
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2024
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IF 4.8
An-Qi Zhu,Ning Luo,Xiao-Ting Zhou,Min Yuan,Chu-Mei Zhang,Tian-Ling Pan,Kun-Ping Li
Along with the increasing prevalence of obesity worldwide, the deleterious effects of high-calorie diet are gradually recognized through more and more epidemiological studies. However, the concealed and chronic causality whitewashes its unhealthy character. Given an ingenious mechanism orchestrates the metabolic adaptation to high-fat high-fructose (HFF) diet and connive its lipotoxicity, in this study, an experimental rat/mouse model of obesity was induced and a comparative transcriptomic analysis was performed to probe the mystery. Our results demonstrated that HFF diet consumption altered the transcriptomic pattern as well as different high-calorie diet fed rat/mouse manifested distinct hepatic transcriptome. Validation with RT-qPCR and Western blotting confirmed that SREBP1-FASN involved in de novo lipogenesis partly mediated metabolic self-adaption. Moreover, hepatic ACSL1-CPT1A-CPT2 pathway involved in fatty acids β-oxidation, played a key role in the metabolic adaption to HFF. Collectively, our findings enrich the knowledge of the chronic adaptation mechanisms and also shed light on future investigations. Meanwhile, our results also suggest that efforts to restore the fatty acids metabolic fate could be a promising avenue to fight against obesity and associated steatosis and insulin resistance challenged by HFF diet.
研究领域:
营养学
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分子生物学
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代谢学
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肥胖研究
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产品关联
DOI
PubMed
高影响因子
ENVIRONMENT INTERNATIONAL
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2025
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IF 9.7
Jianrong Han,Changqian Liu,Zhiyuan Chen,Fengkai Ruan,Fanzheng Xue,Lingxiao Ye,Yi Yu,Zhenghong Zuo,Chengyong He
Metabolic-associated fatty liver disease (MAFLD), linked to lipid dysregulation, poses global health risks. 2,2′,3,4,4′,5′-hexachlorobiphenyl (PCB138) is a persistent organic pollutant that poses potential threats to liver health due to its environmental persistence and bioaccumulation. Theabrown (TB), a natural compound extracted from black tea, exhibits lipid-lowering and antioxidant properties, but its protective effects on PCB138-induced liver injury have not been thoroughly investigated. Following a biphasic experimental design, juvenile male C57BL/6J mice were subjected to chronic PCB138 exposure (100 μg/kg, oral gavage every other day) for 48 weeks, with subsequent administration of TB (225 mg/kg/day) for an 8-week recovery duration. Long-term PCB138 exposure resulted in elevated liver/body weight ratio, hepatic triglyceride/cholesterol accumulation, and histopathological lipidosis, confirming MAFLD progression. Mechanistically, chronic oral exposure to PCB138 induced multi-organ dysregulation, characterized by: (i) intestinal barrier disruption, (ii) gut microbiota dysbiosis, (iii) disruption of the gut-liver bile acid axis accompanied by hepatic accumulation of lithocholic acid (LCA), taurolithocholic acid (TLCA), taurodeoxycholic acid (TDCA), and glycodeoxycholic acid (GDCA), and (iv) upregulated hepatic fatty acid synthase (FASN) expression, thereby accelerating de novo lipogenesis. TB administration for another 8 weeks attenuated these MAFLD manifestations, evidenced by mitigated hepatic lipidosis, repaired intestinal defenses, microbiota normalization, and bile acids rebalance. Using alpha mouse liver 12 (AML12) cells, we demonstrated that GDCA activated sterol regulatory element-binding protein 1 (SREBP1) expression, promoting lipogenesis. This study establishes long-term environmental PCB138 exposure as a driver of MAFLD via gut-liver axis activating lipogenic pathways and microbial-metabolic crosstalk. TB emerges as a potential protective agent by targeting bile acids-mediated SREBP1/FASN signaling, offering insights into environmental pollutant toxicity mitigation and MAFLD management.
研究领域:
环境毒理学
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肝病学
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营养科学
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微生物学
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药理学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
MOLECULAR BIOLOGY REPORTS
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2022
·Vol. 49
·期 4
·2805-2819
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IF 2.742
Lv Yanni,Hong Daojun,Fu Longsheng,Qian Yisong
Background and purpose Nonmuscle myosin heavy chain IIA, played an essential role in the promotion of tight junction injury in vascular endothelial cells under oxygen glucose deprivation condition. Rat microvascular endothelial cells had been confirmed to have the susceptibility to ox-LDL stimulation under OGD condition. We proposed the hypothesis that lipid metabolic reprogramming might be the root cause for damage to RBMCs tight junction. Methods Untargeted shotgun and targeted lipid metabolomics mass spectrometry approaches combined with principal component analysis was applied to better define the lipids contributing to the variance observed between control and different OGD time. The protein expression of tight junction of RBMCs: occludin, claudin-5, and ZO-1 were detected with immunofluorescence staining and western blot. The proof of the interaction between NMMHC IIA and SREBP1 was investigated via GST-pull down, while their specific binding fragments were also confirmed. The regulation mechanism of NMMHC IIA on SREBP1 was investigated to explore downstream regulatory signaling pathways. Results Untargeted and targeted shotgun lipidomics data revealed that OGD might be the conditional factor in reshaping lipid components. Mechanistic studies showed that with the increase of OGD time, PCA analysis of lipidomics obtained from RBMCs indicated their specificity in reshaping lipid components, while ≥80% major lipid components phospholipids and sphingolipids transferred from phospholipids, sphingolipids, and neutral lipids, of which neutral lipids taken the largest proportion with OGD time course. Perturbing reprogramming of lipid composition was less susceptible to OGD condition via knockdown of NMMHC IIA of vascular endothelial cells. Knockdown of NMMHC IIA could promote tight junction defense to OGD condition. NMMHC IIA could directly bind with SREBP1, then could affect sterol regulatory element binding protein-1 to adjust lipid metabolize reprogramming of RBMCs. Conclusions Mechanistic studies showed that perturbing reprogramming of lipid composition could enhance tight junction damage, which was mediated by the opposing effects of NMMHC IIA.
研究领域:
细胞生物学
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分子生物学
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心血管科学
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代谢组学
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产品关联
DOI
PubMed
高影响因子
Food Bioscience
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2024
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IF 4.8
Qiuyan Jiang,Tiehua Zhang,Yuan Liang,Jie Zhang
The role of the pregnane X receptor (PXR) extended beyond regulating drug metabolism and transport, it also played a crucial part in lipid metabolism. Baicalein, a flavonoid derived from Scutellaria baicalensis , was demonstrated anti-inflammatory, anti-cancer, and anti-oxidative stress properties. Recent investigations reported its capacity to enhance lipid metabolism disorders. This study aimed to clarify the mechanism via which baicalein exerted its positive effects on lipid metabolism disorders by targeting PXR. The findings indicated that baicalein facilitated the nuclear translocation of PXR and controlled the expression of its target genes. In HepG2 cells with oleic acid and palmitic acid-induced lipid accumulation, baicalein treatment reduced the production of triglycerides, total cholesterol, and lipid droplets. In addition, it decreased the expression of sterol regulatory element-binding protein 1 (SREBP1), as well as lipogenic enzymes fatty acid synthase (FAS) and stearoyl-CoA desaturase-1 (SCD1). The results of computer simulation indicated that baicalein was a natural ligand of PXR. In conclusion, baicalein might potentially alleviate lipid metabolism disorders by targeting the PXR pathway.
研究领域:
药理学
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细胞生物学
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分子生物学
✓ 已验证
产品关联
DOI
高影响因子
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