BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
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2024
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IF 2.5
Yao Jiang,Wei Wang,Hui Wang,Xiaoru Zhang,Yuling Kong,Yong Q. Chen,Shenglong Zhu
Aberrant adipogenic differentiation is strongly associated with obesity and related metabolic diseases. Elucidating the key factors driving adipogenesis is an effective strategy for identifying novel therapeutic targets for treating metabolic diseases represented by obesity. In this study, transcriptomic techniques were employed to investigate the functional genes that regulate adipogenic differentiation in OP9 cells and 3T3-L1 cells. The findings indicated a notable upregulation of Acsl1 expression throughout the adipogenic differentiation process. Knocking down Acsl1 led to a decrease in the expression of genes associated with adipogenesis and a reduction in triglyceride accumulation. Additionally, Acsl1 overexpression promoted adipocyte differentiation and adipose-specific overexpression of Acsl1 markedly aggravated steatosis induced by a high-fat diet. Mechanistically, Cyp2f2, Dusp23 and Gstm2 are the crucial genes implicated in Acsl1-induced adipogenic differentiation. The findings of this study indicate that Acsl1 promotes adipogenesis and could serve as a potential therapeutic target for treating obesity and related metabolic disorders.
研究领域:
分子生物学
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细胞生物学
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代谢
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肥胖研究
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DOI
高影响因子
Cell Reports
·
2025
·
IF 6.9
Zu-Guo Zheng,Yi-Ping Zhang,Xiao-Yu Zhang,Meng-Yao Qin,Yin-Yue Xu,He Wu,Run-Qing Liu,Qiu-Yi Wu,Ming-Su Wang,Chong Zhang,Yue-Qin Zheng,Jian-Ye Dai,Ping Li,Hua Yang
Sterols target sterol-sensing domain (SSD) proteins to lower cholesterol and circulating and hepatic triglyceride levels, but the mechanism remains unclear. In this study, we identify acyl-coenzyme A (CoA) synthetase long-chain family member 1 (ACSL1) as a direct target of ergosterol (ES). The C-terminal domain of ACSL1 undergoes conformational changes from closed to open, and ES may target the drug-binding pocket in the acetyl-CoA synthetase-like domain 1 (ASLD1) of ACSL1 to stabilize the closed conformation and maintain its activity. Moreover, ES is mainly enriched in the mitochondria and promotes fatty acid β-oxidation through ACSL1 allosteric activation. Structure-activity relationship analysis reveals how different structural sterols interact with the sterol-sensing domain-containing protein (SCAP) and ACSL1, explaining their regulatory effects on lipid metabolism. Moreover, our findings reveal that the combination of SCAP inhibitor 25-hydroxycholesterol (25-HC) and ES has a stronger lipid-lowering effect than alone.
研究领域:
分子生物学
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脂质代谢
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药理学
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肝病学
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产品关联
DOI
PubMed
高影响因子
Viruses-Basel
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2021
·Vol. 13
·期 12
·2383
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IF 5.048
Huawei Xia,Zeming Zhang,Fuping You
Murine hepatitis virus strain A59 (MHV-A59) was shown to induce pyroptosis, apoptosis, and necroptosis of infected cells, especially in the murine macrophages. However, whether ferroptosis, a recently identified form of lytic cell death, was involved in the pathogenicity of MHV-A59 is unknown. We utilized murine macrophages and a C57BL/6 mice intranasal infection model to address this. In primary macrophages, the ferroptosis inhibitor inhibited viral propagation, inflammatory cytokines released, and cell syncytia formed after MHV-A59 infection. In the mouse model, we found that in vivo administration of liproxstatin-1 ameliorated lung inflammation and tissue injuries caused by MHV-A59 infection. To find how MHV-A59 infection influenced the expression of ferroptosis-related genes, we performed RNA-seq in primary macrophages and found that MHV-A59 infection upregulates the expression of the acyl-CoA synthetase long-chain family member 1 (ACSL1), a novel ferroptosis inducer. Using ferroptosis inhibitors and a TLR4 inhibitor, we showed that MHV-A59 resulted in the NF-kB-dependent, TLR4-independent ACSL1 upregulation. Accordingly, ACSL1 inhibitor Triacsin C suppressed MHV-A59-infection-induced syncytia formation and viral propagation in primary macrophages. Collectively, our study indicates that ferroptosis inhibition protects hosts from MHV-A59 infection. Targeting ferroptosis may serve as a potential treatment approach for dealing with hyper-inflammation induced by coronavirus infection.Keywords:coronavirus;mouse hepatitis virus (MHV);ferroptosis;therapy
研究领域:
病毒学
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免疫学
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药理学
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产品关联
DOI
PubMed
高影响因子
Journal of Functional Foods
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2022
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IF 5.223
Jie Gao,Xue Gu,Manqian Zhang,Xingwang Zu,Fukui Shen,Xiaotao Hou,Erwei Hao,Gang Bai
Lipid metabolic disorders impair quality of life in humans. Ferulic acid (FA), a ubiquitous phenolic nutrient existing in daily human food, exerts beneficial effects in improving glucose and lipid metabolisms. However, the underlying mechanisms are still unclear. In this study, FA treatment significantly attenuated metabolic disorders in db/db mice. Nontargeted metabolomics results suggested the participation of lipid metabolism regulation. Target fishing identified long-chain acyl-CoA synthase 1 (ACSL1) as the target of FA. FA provided a free fatty acid residue as the substrate of ACSL1 and triggered the mitochondrial membrane distribution of ACSL1. This distribution led to the upregulation of adenosine monophosphate (AMP)/adenosine triphosphate (ATP), which was sensed by AMP-activated protein kinase (AMPK) and in turn caused AMPK phosphorylation, further inhibiting the synthesis of triglyceride and cholesterol. In conclusion, FA might be explored as a potential complementary and alternative nutrient agent targeting ACSL1 to ameliorate lipid metabolism in diabetes.
研究领域:
药理学
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代谢
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营养学
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糖尿病
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产品关联
DOI
高影响因子
Communications Biology
·
2026
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IF 5.8
Nie Hong-Yu,Zou Ming-Jie,Zhao Meng-Fei,Tang Yi-Ping,Wang Nan-Nan,Zhou Zi-Yue,Zhang Jing-Zi,Li Chao-Jun,Fang Lei
Obesity can be classified into metabolically healthy obesity (MHO) and metabolically unhealthy obesity (MUO), but the molecular mechanisms remain unclear. We identify geranylgeranyl pyrophosphate (GGPP), a metabolite of the hepatic mevalonate pathway involved in cholesterol biosynthesis, as a critical mediator that distinguishes MUO from MHO. In this study, Long-term feeding of mice with starch oleate significantly upregulated the expression of geranylgeranyl diphosphate synthase (Ggpps), resulting in elevated GGPP levels. Liver-specific deletion of Ggpps reduced GGPP and selectively attenuated adipocyte hypotrophy while specifically enhancing insulin sensitivity in epididymal white adipose tissue (eWAT). Mechanistic studies suggest that GGPP modulates acyl-CoA synthetase long-chain family member 1 (ACSL1) in eWAT through non-covalent binding rather than protein geranylgeranylation, thereby inhibiting its translocation from the endoplasmic reticulum to mitochondria. The retention of ACSL1 in the ER induces eWAT-specific adipose remodeling by promoting triglyceride (TG) synthesis and suppressing lipid oxidation. These findings establish a “liver-adipose” axis mediated by the hepatic metabolite GGPP via its non-covalent interaction with adipocyte ACSL1, highlighting potential therapeutic targets for metabolic dysfunction associated with metabolically unhealthy obesity.
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DOI
PubMed
高影响因子
JOURNAL OF NUTRITIONAL BIOCHEMISTRY
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2024
·
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
ONCOLOGY REPORTS
·
2020
·Vol. 44
·期 6
·2595-2609
·
IF 3.417
Gang Wang,Yang Yu,Yu‑Zhu Wang,Zhi‑Min Zhu,Pei‑Hao Yin,Ke Xu
Although previous studies have demonstrated that triterpenoids, such as betulinic acid (BA), can inhibit tumor cell growth, their potential targets in colorectal cancer (CRC) metabolism have not been systematically investigated. In the present study, BA‑loaded nanoliposomes (BA‑NLs) were prepared, and their effects on CRC cell lines were evaluated. The aim of the present study was to determine the anticancer mechanisms of action of BA‑NLs in fatty acid metabolism‑mediated glycolysis, and investigate the role of key targets, such as acyl‑CoA synthetase (ACSL), carnitine palmitoyltransferase (CPT) and acetyl CoA, in promoting glycolysis, which is activated by inducing hexokinase (HK), phosphofructokinase‑1 (PFK‑1), phosphoenolpyruvate (PEP) and pyruvate kinase (PK) expression. The results demonstrated that BA‑NLs significantly suppressed the proliferation and glucose uptake of CRC cells by regulating potential glycolysis and fatty acid metabolism targets and pathways, which forms the basis of the anti‑CRC function of BA‑NLs. Moreover, the effects of BA‑NLs were further validated by demonstrating that the key targets of HK2, PFK‑1, PEP and PK isoenzyme M2 (PKM2) in glycolysis, and of ACSL1, CPT1a and PEP in fatty acid metabolism, were blocked by BA‑NLs, which play key roles in the inhibition of glycolysis and fatty acid‑mediated production of pyruvate and lactate. The results of the present study may provide a deeper understanding supporting the hypothesis that liposomal BA may regulate alternative metabolic pathways implicated in CRC adjuvant therapy.
研究领域:
肿瘤学
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药理学
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代谢
✓ 已验证
产品关联
DOI
PubMed
高影响因子
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