scholarly journals PHLPP1 promotes neutral lipid accumulation through AMPK/ChREBP dependent lipid uptake and fatty acid synthesis pathways

iScience ◽  
2022 ◽  
pp. 103766
Author(s):  
Keerthana B ◽  
Raghavender Medishetti ◽  
Jyothi Kotha ◽  
Parameshwar Behera ◽  
Kanika Chandra ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Neutral Lipid ◽  
Fatty Acid Synthesis ◽  
Lipid Accumulation ◽  
Acid Synthesis ◽  
Lipid Uptake

scholarly journals Systematic mapping of genetic interactions for de novo fatty acid synthesis

2019 ◽  
Author(s):  
Michael Aregger ◽  
Keith A. Lawson ◽  
Maximillian Billmann ◽  
Michael Costanzo ◽  
Amy H. Y. Tong ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Fatty Acid ◽  
Fatty Acid Synthesis ◽  
De Novo ◽  
Strong Dependence ◽  
Acid Synthesis ◽  
Protein Glycosylation ◽  
Genetic Interactions ◽  
Lipid Uptake ◽  
Functional Relationships

ABSTRACTThe de novo synthesis of fatty acids has emerged as a therapeutic target for various diseases including cancer. While several translational efforts have focused on direct perturbation of de novo fatty acid synthesis, only modest responses have been associated with mono-therapies. Since cancer cells are intrinsically buffered to combat metabolic stress, cells may adapt to loss of de novo fatty acid biosynthesis. To explore cellular response to defects in fatty acid synthesis, we used pooled genome-wide CRISPR screens to systematically map genetic interactions (GIs) in human HAP1 cells carrying a loss-of-function mutation in FASN, which catalyzes the formation of long-chain fatty acids. FASN mutant cells showed a strong dependence on lipid uptake that was reflected by negative GIs with genes involved in the LDL receptor pathway, vesicle trafficking, and protein glycosylation. Further support for these functional relationships was derived from additional GI screens in query cell lines deficient for other genes involved in lipid metabolism, including LDLR, SREBF1, SREBF2, ACACA. Our GI profiles identified a potential role for a previously uncharacterized gene LUR1 (C12orf49) in exogenous lipid uptake regulation. Overall, our data highlights the genetic determinants underlying the cellular adaptation associated with loss of de novo fatty acid synthesis and demonstrate the power of systematic GI mapping for uncovering metabolic buffering mechanisms in human cells.

scholarly journals Acetate Affects the Process of Lipid Metabolism in Rabbit Liver, Skeletal Muscle and Adipose Tissue

Animals ◽  
2019 ◽  
Vol 9 (10) ◽  
pp. 799 ◽  
Author(s):  
Lei Liu ◽  
Chunyan Fu ◽  
Fuchang Li
Keyword(s):  
Fatty Acid ◽  
Fatty Acid Oxidation ◽  
Fatty Acid Synthesis ◽  
Lipid Accumulation ◽  
Acid Synthesis ◽  
Control Group ◽  
Acid Oxidation ◽  
Signal Pathways ◽  
Peroxisome Proliferator ◽  
Acid Uptake

Short-chain fatty acids (SCFAs) (a microbial fermentation production in the rabbit gut) have an important role in many physiological processes, which may be related to the reduced body fat of rabbits. In the present experiment, we study the function of acetate (a major SCFA in the rabbit gut) on fat metabolism. Ninety rabbits (40 days of age) were randomly divided into three groups: a sham control group (injection of saline for four days); a group experiencing subcutaneous injection of acetate for four days (2 g/kg BM per day, one injection each day, acetate); and a pair-fed sham treatment group. The results show that acetate-inhibited lipid accumulation by promoting lipolysis and fatty acid oxidation and inhibiting fatty acid synthesis. Activated G protein-coupled receptor 41/43, adenosine monophosphate activated protein kinase (AMPK) and extracellular-signal-regulated kinase (ERK) 1/2 signal pathways were likely to participate in the regulation in lipid accumulation of acetate. Acetate reduced hepatic triglyceride content by inhibiting fatty acid synthesis, enhancing fatty acid oxidation and lipid output. Inhibited peroxisome proliferator-activated receptor α (PPARα) and activated AMPK and ERK1/2 signal pathways were related to the process in liver. Acetate reduced intramuscular triglyceride level via increasing fatty acid uptake and fatty acid oxidation. PPARα was associated with the acetate-reduced intracellular fat content.

scholarly journals Yamogenin in fenugreek inhibits lipid accumulation through the suppression of gene expression in fatty acid synthesis in hepatocytes

2014 ◽  
Vol 78 (7) ◽  
pp. 1231-1236 ◽  
Author(s):  
Sayaka Moriwaki ◽  
Hiroki Murakami ◽  
Nobuyuki Takahashi ◽  
Taku Uemura ◽  
Keiko Taketani ◽  
...  
Keyword(s):  
Gene Expression ◽  
Fatty Acid ◽  
Fatty Acid Synthesis ◽  
Lipid Accumulation ◽  
Acid Synthesis ◽  
Suppression Of Gene Expression

scholarly journals Oleiferasaponin A2, a Novel Saponin from Camellia oleifera Abel. Seeds, Inhibits Lipid Accumulation of HepG2 Cells Through Regulating Fatty Acid Metabolism

Molecules ◽  
2018 ◽  
Vol 23 (12) ◽  
pp. 3296 ◽  
Author(s):  
Tai-Mei Di ◽  
Shao-Lan Yang ◽  
Feng-Yu Du ◽  
Lei Zhao ◽  
Xiao-Han Li ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Fatty Acid Metabolism ◽  
Fatty Acid Synthesis ◽  
Lipid Accumulation ◽  
Acid Metabolism ◽  
Acid Synthesis ◽  
Triterpenoid Saponin ◽  
Camellia Oleifera ◽  
Medicinal Value ◽  
Hepg2 Cell Lines

A new triterpenoid saponin, named oleiferasaponin A2, was isolated and identified from Camellia oleifera defatted seeds. Oleiferasaponin A2 exhibited anti-hyperlipidemic activity on HepG2 cell lines. Further study of the hypolipidemic mechanism showed that oleiferasaponin A2 inhibited fatty acid synthesis by significantly down-regulating the expression of SREBP-1c, FAS and FAS protein, while dramatically promoting fatty acid β-oxidation by up-regulating the expression of ACOX-1, CPT-1 and ACOX-1 protein. Our results demonstrate that the oleiferasaponin A2 possesses potential medicinal value for hyperlipidemia treatment.

In silico Mapping and Structure Analysis of Key Enzyme Genes in Fatty Acid Synthesis of Soybean

2009 ◽  
Vol 35 (10) ◽  
pp. 1942-1947
Author(s):  
Wan-Kun SONG ◽  
Ming-Xi ZHU ◽  
Yang-Lin ZHAO ◽  
Jing WANG ◽  
Wen-Fu LI ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Structure Analysis ◽  
Fatty Acid Synthesis ◽  
In Silico ◽  
Acid Synthesis ◽  
In Silico Mapping ◽  
Key Enzyme

BET Inhibition Induces Vulnerability to MCL1 Targeting Through Upregulation of Fatty Acid Synthesis Pathway in Breast Cancer

2020 ◽  
Author(s):  
Gonghong Yan ◽  
Augustin Luna ◽  
Heping Wang ◽  
Behnaz Bozorgui ◽  
Xubin Li ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Fatty Acid ◽  
Fatty Acid Synthesis ◽  
Acid Synthesis ◽  
Fatty Acid Synthesis Pathway

The Potential of 11C-acetate PET for Monitoring the Fatty Acid Synthesis Pathway in Tumors

2013 ◽  
Vol 14 (3) ◽  
pp. 300-312 ◽  
Author(s):  
Laura M. DeFord-Watts ◽  
Akiva Mintz ◽  
Steven J. Kridel
Keyword(s):  
Fatty Acid ◽  
Fatty Acid Synthesis ◽  
Acid Synthesis ◽  
Fatty Acid Synthesis Pathway
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