Algal Research-Biomass Biofuels and Bioproducts
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2018
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IF 3.745
Xiang Wang,Wei Wei,Nian-Jing Li,Wasiqi Yuan,Yu Ding,Wei-Dong Yang,Jie-Sheng Liu,Srinivasan Balamurugan,Hong-Ye Li
Microalgal metabolic engineering holds great promise for algal biofuels. However, identification of the key lipid metabolic target remains challenging due to its complex regulation. In this study, we advocated an alternative strategy that potentially rewired lipid metabolism by unprecedented mechanisms. PNPLA3 , a human protein associated with non-alcoholic fatty liver disease (NAFLD), was firstly tested in microalgae for enhancing lipid accumulation . HsPNPLA3 was synthesized with a site mutation (I148M) and expressed in a model diatom Phaeodactylum tricornutum . Heterogeneous HsPNPLA3-I148M was successfully integrated, transcribed and expressed. Lipidomic analyses revealed that HsPNPLA3-I148M significantly elevated TAG content by 1.55-fold in algae, while algal growth and photosynthetic rate were not impaired. Fatty acid profile showed that content of C16:0, C18:1 and C20:4 was increased by 1.43-, 4.18- and 4.3-fold, respectively, which implied that HsPNPLA3-I148M might regulate the fatty acid substrate preference. Overall, the findings demonstrated that human PNPLA3 played a potential role in elevating TAG accumulation by regulating lipogenic enzymes and provide unprecedented insights into its functional significance.
研究领域:
生物化学
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生物技术
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代谢工程
✓ 已验证
DOI
高影响因子
ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS
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2022
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IF 4.114
Pan Li,Yuwei Chen,Xiumei Ke,Ruoyu Zhang,Ling Zuo,Meng Wang,Zhiwei Chen,Xianqin Luo,Jianwei Wang
Baicalin is a flavonoid compound abundant in multiple edible and medicinal plants such as Scutellaria baicalensis Georgi . In this study, we provide evidence to support the fact that baicalin ameliorates alcohol-induced hepatic steatosis via regulating SREBP1c elicited PNPLA3 competitive binding to ATGL . Results showed that baicalin significantly attenuated the development of metabolic disorders and hepatic steatosis in alcohol-induced rats after four weeks of treatment. It was evident that baicalin treatment significantly normalized the serous contents of hepatic triglyceride (TG), alanine aminotransferase (ALT), and aspartate aminotransferase (AST), and attenuated the increase of hepatic vacuolization and Oil Red O staining area caused by alcohol. Meanwhile, baicalin relieves alcohol-induced hepatic fibrosis by masson staining and RT-qPCR analysis. Mechanistically, alcohol aggravated the nuclear expression of SREBP1c, which contributed to the high expression of PNPLA3 and FASN , thereby enhancing the binding of PNPLA3 to ABHD5 , and indirectly impairing the binding ability between ATGL and ABHD5, ultimately causing a decline in the hydrolysis capacity in liver lipid droplets . As expected, these alcohol-induced pathobolism were reversed by baicalin treatment both in vivo and in vitro . In conclusion, this study has demonstrated that baicalin can protect against alcohol-induced hepatic lipid accumulation by activating hepatic lipolysis via suppressing SREBP1c elicited PNPLA3 competitive binding to ATGL. Baicalin is a promising natural product for preventing alcohol-induced hepatic steatosis.
研究领域:
药理学
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肝病学
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代谢学
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分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Clinical and Molecular Hepatology
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2024
·Vol. 30
·期 4
·863
·
IF 14
Baokai Sun,Xiaoqian Ding,Jie Tan,Jie Zhang,Xueru Chu,Shuimi Zhang,Shousheng Liu,Zhenzhen Zhao,Shiying Xuan,Yongning Xin,Likun Zhuang
Backgrounds/Aims Transmembrane 6 superfamily member 2 (TM6SF2) E167K variant is closely associated with the occurrence and development of metabolic dysfunction-associated steatotic liver disease (MASLD). However, the role and mechanism of TM6SF2 E167K variant during MASLD progression are not yet fully understood. Methods The Tm6sf2 167K knock-in (KI) mice were subjected to high-fat diet (HFD). Hepatic lipid levels of Tm6sf2 167K KI mice were detected by lipidomics analysis. Thin-layer chromatography (TLC) was used to measure the newly synthesized triglyceride (TG) and phosphatidylcholine (PC). Results The TM6SF2 E167K variant significantly aggravated hepatic steatosis and injury in HFD-induced mice. Decreased polyunsaturated PC level and increased polyunsaturated TG level were found in liver tissue of HFD-induced Tm6sf2 167K KI mice. Mechanistic studies demonstrated that the TM6SF2 E167K variant increased the interaction between TM6SF2 and PNPLA3, and impaired PNPLA3-mediated transfer of polyunsaturated fatty acids (PUFAs) from TG to PC. The TM6SF2 E167K variant increased the level of fatty acid-induced malondialdehyde and reactive oxygen species, and decreased fatty acid-downregulated cell membrane fluidity. Additionally, the TM6SF2 E167K variant decreased the level of hepatic PC containing C18:3, and dietary supplementation of PC containing C18:3 significantly attenuated the TM6SF2 E167K-induced hepatic steatosis and injury in HFD-fed mice. Conclusions The TM6SF2 E167K variant could promote its interaction with PNPLA3 and inhibit PNPLA3-mediated transfer of PUFAs from TG to PC, resulting in the hepatic steatosis and injury during MASLD progression. PC containing C18:3 could act as a potential therapeutic supplement for MASLD patients carrying the TM6SF2 E167K variant.
研究领域:
肝病学
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分子生物学
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代谢
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脂质代谢
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遗传学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIOMEDICINE & PHARMACOTHERAPY
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2018
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IF 3.457
Qingqing Yu,Yayun Liu,Yufei Wu,Yong Chen
Aims Curcumin is a polyphenol compound with many pharmacological activities including antioxidant, lipid-loweing and liver protective. Dihydrocurcumin (DHC) is one of the major metabolites of curcumin. So far, the pharmacological activity of DHC has not been reported. Here, we evaluate the effects of DHC on oleic acid (OA)-induced lipid accumulation, oxidative stress and insulin resistance and the underlying mechanism in L02 and HepG2 cells. Main methods OA-induced L02 and HepG2 cells were used as the in vitro model of nonalcoholic fatty liver disease (NAFLD). Lipid accumulation, oxidative stress, glucose uptake and cell inflammation were evaluated by cellular biochemical assay, respectively. Signaling pathways involved in lipid metabolism including peroxisome proliferator activated receptor-α (PPARα), the sterol regulatory element binding protein-1C (SREBP-1C) and patatin-like phospholipase domain containing 3 (PNPLA3), glucose uptake including phosphatidylinositol 3-kinase (PI3K) and phosphorylated serine-threonine protein kinase (pAKT), and oxidative stress including nuclear factor E2-related factor 2 (Nrf2), cytochrome P450 4A (CYP4A) and 2E1 (CYP2E1) were investigated by western blotting and RT-qPCR, respectively. Key findings DHC decreased the levels of cellular triglycerides (TG) by regulating the mRNA and protein expression levels of SREBP-1C , PNPLA3 and PPARα . At the same time, DHC improved the hepatocellular glucose uptake by increasing the protein expression levels of pAKT and PI3K. Furthermore, DHC reduced the levels of cellular NO and ROS via Nrf2 signaling pathways. Significance The present study firstly revealed that DHC ameliorated OA-induced steatosis through regulating the lipid metabolism, oxidative stress and insulin resistance in HepG2 and L02 cells.
研究领域:
药理学
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细胞生物学
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代谢
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肝脏疾病
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）