scholarly journals Ganoderma Lucidum Polysaccharide Peptide Alleviates Hepatoteatosis via Modulating Bile Acid Metabolism Dependent on FXR-SHP/FGF

2018 ◽  
Vol 49 (3) ◽  
pp. 1204-1220 ◽  
Author(s):  
Dandan Zhong ◽  
Zhengwei Xie ◽  
Boyue Huang ◽  
Shuai Zhu ◽  
Guoqian Wang ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Bile Acid ◽  
Mouse Model ◽  
Therapeutic Effect ◽  
Fatty Acid Synthesis ◽  
Hepg2 Cells ◽  
Ganoderma Lucidum ◽  
Acid Metabolism ◽  
Acid Synthesis ◽  
Primary Hepatocytes

Background/Aims: Non-alcoholic fatty liver disease (NAFLD) encompasses a series of pathologic changes ranging from steatosis to steatohepatitis, which may progress to cirrhosis and hepatocellular carcinoma. The purpose of this study was to determine whether ganoderma lucidum polysaccharide peptide (GLPP) has therapeutic effect on NAFLD. Methods: Ob/ ob mouse model and ApoC3 transgenic mouse model were used for exploring the effect of GLPP on NAFLD. Key metabolic pathways and enzymes were identified by metabolomics combining with KEGG and PIUmet analyses and key enzymes were detected by Western blot. Hepatosteatosis models of HepG2 cells and primary hepatocytes were used to further confirm the therapeutic effect of GLPP on NAFLD. Results: GLPP administrated for a month alleviated hepatosteatosis, dyslipidemia, liver dysfunction and liver insulin resistance. Pathways of glycerophospholipid metabolism, fatty acid metabolism and primary bile acid biosynthesis were involved in the therapeutic effect of GLPP on NAFLD. Detection of key enzymes revealed that GLPP reversed low expression of CYP7A1, CYP8B1, FXR, SHP and high expression of FGFR4 in ob/ob mice and ApoC3 mice. Besides, GLPP inhibited fatty acid synthesis by reducing the expression of SREBP1c, FAS and ACC via a FXR-SHP dependent mechanism. Additionally, GLPP reduced the accumulation of lipid droplets and the content of TG in HepG2 cells and primary hepatocytes induced by oleic acid and palmitic acid. Conclusion: GLPP significantly improves NAFLD via regulating bile acid synthesis dependent on FXR-SHP/FGF pathway, which finally inhibits fatty acid synthesis, indicating that GLPP might be developed as a therapeutic drug for NAFLD.

A novel acetyl-CoA carboxylase inhibitor reduces de novo fatty acid synthesis in HepG2 cells and rat primary hepatocytes

2007 ◽  
Vol 468 (1) ◽  
pp. 44-48 ◽  
Author(s):  
Yoshinori Sugimoto ◽  
Yoshimitsu Naniwa ◽  
Takayuki Nakamura ◽  
Hirotsugu Kato ◽  
Masanori Yamamoto ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Fatty Acid Synthesis ◽  
Hepg2 Cells ◽  
De Novo ◽  
Acid Synthesis ◽  
Acetyl Coa Carboxylase ◽  
Primary Hepatocytes ◽  
Acetyl Coa ◽  
Rat Primary Hepatocytes

miR-497 regulates fatty acid synthesis via LATS2 in bovine mammary epithelial cells

2020 ◽  
Vol 11 (10) ◽  
pp. 8625-8636
Author(s):  
Zhi Chen ◽  
Shuangfeng Chu ◽  
Yusheng Liang ◽  
Tianle Xu ◽  
Yujia Sun ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Fatty Acid Metabolism ◽  
Fatty Acid Synthesis ◽  
Milk Fat ◽  
Acid Metabolism ◽  
Mammary Epithelial Cells ◽  
Acid Synthesis ◽  
Mammary Epithelial ◽  
Bovine Mammary Epithelial Cells ◽  
Fat Synthesis

Both mRNA and miRNA play an important role in the regulation of mammary fatty acid metabolism and milk fat synthesis.

scholarly journals The Bactericidal Fatty Acid Mimetic 2CCA-1 Selectively Targets Pneumococcal Extracellular Polyunsaturated Fatty Acid Metabolism

mBio ◽  
2020 ◽  
Vol 11 (6) ◽  
pp. e03027-20
Author(s):  
Elisabeth Reithuber ◽  
Priyanka Nannapaneni ◽  
Olena Rzhepishevska ◽  
Anders E. G. Lindgren ◽  
Oleksandr Ilchenko ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Fatty Acid ◽  
Streptococcus Pneumoniae ◽  
Fatty Acid Synthesis ◽  
Acid Metabolism ◽  
Acid Synthesis ◽  
Endogenous Fatty Acid ◽  
Content Type ◽  
Endogenous Fatty Acid Synthesis ◽  
Phospholipid Species

ABSTRACTStreptococcus pneumoniae, a major cause of pneumonia, sepsis, and meningitis worldwide, has the nasopharynges of small children as its main ecological niche. Depletion of pneumococci from this niche would reduce the disease burden and could be achieved using small molecules with narrow-spectrum antibacterial activity. We identified the alkylated dicyclohexyl carboxylic acid 2CCA-1 as a potent inducer of autolysin-mediated lysis of S. pneumoniae, while having low activity against Staphylococcus aureus. 2CCA-1-resistant strains were found to have inactivating mutations in fakB3, known to be required for uptake of host polyunsaturated fatty acids, as well as through inactivation of the transcriptional regulator gene fabT, vital for endogenous, de novo fatty acid synthesis regulation. Structure activity relationship exploration revealed that, besides the central dicyclohexyl group, the fatty acid-like structural features of 2CCA-1 were essential for its activity. The lysis-inducing activity of 2CCA-1 was considerably more potent than that of free fatty acids and required growing bacteria, suggesting that 2CCA-1 needs to be metabolized to exert its antimicrobial activity. Total lipid analysis of 2CCA-1 treated bacteria identified unique masses that were modeled to 2CCA-1 containing lysophosphatidic and phosphatidic acid in wild-type but not in fakB3 mutant bacteria. This suggests that 2CCA-1 is metabolized as a fatty acid via FakB3 and utilized as a phospholipid building block, leading to accumulation of toxic phospholipid species. Analysis of FabT-mediated fakB3 expression elucidates how the pneumococcus could ensure membrane homeostasis and concurrent economic use of host-derived fatty acids.IMPORTANCE Fatty acid biosynthesis is an attractive antibiotic target, as it affects the supply of membrane phospholipid building blocks. In Streptococcus pneumoniae, it is not sufficient to target only the endogenous fatty acid synthesis machinery, as uptake of host fatty acids may bypass this inhibition. Here, we describe a small-molecule compound, 2CCA-1, with potent bactericidal activity that upon interactions with the fatty acid binding protein FakB3, which is present in a limited number of Gram-positive species, becomes metabolized and incorporated as a toxic phospholipid species. Resistance to 2CCA-1 developed specifically in fakB3 and the regulatory gene fabT. These mutants reveal a regulatory connection between the extracellular polyunsaturated fatty acid metabolism and endogenous fatty acid synthesis in S. pneumoniae, which could ensure balance between efficient scavenging of host polyunsaturated fatty acids and membrane homeostasis. The data might be useful in the identification of narrow-spectrum treatment strategies to selectively target members of the Lactobacillales such as S. pneumoniae.

Clove extract functions as a natural fatty acid synthesis inhibitor and prevents obesity in a mouse model

2017 ◽  
Vol 8 (8) ◽  
pp. 2847-2856 ◽  
Author(s):  
Yiran Ding ◽  
Zhennan Gu ◽  
Yihe Wang ◽  
Shunhe Wang ◽  
Haiqin Chen ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Medicinal Plants ◽  
Mouse Model ◽  
Chronic Diseases ◽  
Fatty Acid Synthesis ◽  
Acid Synthesis ◽  
Synthesis Inhibitor ◽  
Clove Extract ◽  
Natural Fatty Acid

Numerous medicinal plants have been reported to prevent various chronic diseases.

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