BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR AND CELL BIOLOGY OF LIPIDS
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2025
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IF 3.3
Xinjing Shi,Qingjing Gao,Wenjing Lu,Yuning Xie,Haolin Zhang,Dong Zhang,Yuning Liu,Qiang Weng
SREBP1 (sterol regulatory element binding protein 1) plays an important role in maintaining lipid balance in mammals. Previous research showed that androgen significantly regulated the secretion of lipid-rich musky odor substances from the scented glands of muskrats. Our investigation provides insights into the pathways through which androgen induces SREBP1 expression and affects seasonal changes in triglyceride synthesis in muskrat scented glands. During the breeding season, pronounced Oil Red O staining was confirmed in the scented glandular tissues, and transmission electron microscopy displayed a marked increase in lipid droplets. The scented glands exhibited a higher triglyceride content, which coincided with augmented circulating testosterone, dihydrotestosterone, as well as increased scented glandular testosterone and dihydrotestosterone concentrations. Transcriptomic, proteomic and metabolomic analyses of the scented glands revealed associations with fatty acid biosynthesis, while plasma metabolomic data indicated an increase in metabolites serving as precursors during the breeding season for de novo fatty acid synthesis. Expression levels of genes and proteins related to lipid synthesis and lipid droplets, as well as FASN activity, were significantly elevated in the breeding season. Immunolocalization studies demonstrated the presence of these proteins in glandular and epithelial cells in both seasons. Moreover, in vitro treatment of the scented glandular cells with testosterone resulted in elevated expressions of triglyceride synthesis-related genes. These findings suggested that androgen modulates triglyceride synthesis to enhance lipid droplet formation via the AR-SREBP1-FASN Axis in the scented glands of muskrats, thereby shedding light on the hormonal regulation of lipid metabolism in seasonal breeders.
研究领域:
分子生物学
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内分泌学
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生物化学
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生殖生物学
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比较生理学
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脂质代谢
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动物生理学
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产品关联
DOI
PubMed
高影响因子
KOREAN JOURNAL OF PHYSIOLOGY & PHARMACOLOGY
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2024
·Vol. 28
·期 3
·219-227
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IF 1.6
Peiyu Lin,Xiyue Yang,Linghui Wang,Xin Zou,Lingli Mu,Cangcang Xu,Xiaoping Yang
Bladder cancer remains the 10th most common cancer worldwide. In recent years, metformin has been found to have potential anti-bladder cancer activity while high concentration of IC 50 at millimolar level is needed, which could not be reached by regular oral administration route. Thus, higher efficient agent is urgently demanded for clinically treating bladder cancer. Here, by conjugating artesunate to metformin, a novel artesunate-metformin dimer triazine derivative AM2 was designed and synthesized. The inhibitory effect of AM2 on bladder cancer cell line T24 and the mechanism underlying was determined. Anti-tumor activity of AM2 was assessed by MTT, cloning formation and wound healing assays. Decreasing effect of AM2 on lipogenesis was determined by oil red O staining. The protein expressions of Clusterin, SREBP1 and FASN in T24 cells were evaluated by Western blotting. The results show that AM2 significantly inhibited cell proliferation and migration at micromolar level, much higher than parental metformin. AM2 reduced lipogenesis and down-regulated the expressions of Clusterin, SREBP1 and FASN. These results suggest that AM2 inhibits the growth of bladder cancer cells T24 by inhibiting cellular lipogenesis associated with the Clusterin/SREBP1/FASN signaling pathway.
研究领域:
肿瘤学
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药理学
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细胞生物学
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DOI
PubMed
高影响因子
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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DOI
PubMed
高影响因子
ENVIRONMENT INTERNATIONAL
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2025
·
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
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