2 H2 O incorporation into hepatic acetyl-CoA and de novo lipogenesis as measured by Krebs cycle-mediated 2 H-enrichment of glutamate and glutamine

2011 ◽  
Vol 66 (6) ◽  
pp. 1526-1530 ◽  
Author(s):  
Ana Maria Silva ◽  
Fatima Martins ◽  
John G. Jones ◽  
Rui Carvalho
Keyword(s):  
De Novo ◽  
Krebs Cycle ◽  
De Novo Lipogenesis ◽  
Acetyl Coa

scholarly journals Transfer of glucose hydrogens via acetyl-CoA, malonyl-CoA, and NADPH to fatty acids during de novo lipogenesis

2019 ◽  
Vol 60 (12) ◽  
pp. 2050-2056 ◽  
Author(s):  
Getachew Debas Belew ◽  
Joao Silva ◽  
Joao Rito ◽  
Ludgero Tavares ◽  
Ivan Viegas ◽  
...  
Keyword(s):  
Fatty Acids ◽  
De Novo ◽  
De Novo Lipogenesis ◽  
Acetyl Coa ◽  
Malonyl Coa

scholarly journals Loss of Acot12 contributes to NAFLD independent of lipolysis of adipose tissue

2021 ◽  
Author(s):  
Sujeong Park ◽  
Jinsoo Song ◽  
In-Jeoung Baek ◽  
Kyu Yun Jang ◽  
Chang Yeob Han ◽  
...  
Keyword(s):  
De Novo ◽  
Interaction Analysis ◽  
Cholesterol Biosynthesis ◽  
De Novo Lipogenesis ◽  
Cholesterol Trafficking ◽  
Acetyl Coa ◽  
Nonalcoholic Fatty Liver ◽  
Vacuolar Protein ◽  
Specific Deletion ◽  
Stimulation Of

AbstractIn this study, we hypothesized that deregulation in the maintenance of the pool of coenzyme A (CoA) may play a crucial role in the pathogenesis of nonalcoholic fatty liver disease (NAFLD). Specific deletion of Acot12 (Acot12−/−), the major acyl-CoA thioesterase, induced the accumulation of acetyl-CoA and resulted in the stimulation of de novo lipogenesis (DNL) and cholesterol biosynthesis in the liver. KEGG pathway analysis suggested PPARα signaling as the most significantly enriched pathway in Acot12−/− livers. Surprisingly, the exposure of Acot12−/− hepatocytes to fenofibrate significantly increased the accumulation of acetyl-CoA and resulted in the stimulation of cholesterol biosynthesis and DNL. Interaction analysis, including proximity-dependent biotin identification (BioID) analysis, suggested that ACOT12 may directly interact with vacuolar protein sorting-associated protein 33A (VPS33A) and play a role in vesicle-mediated cholesterol trafficking and the process of lysosomal degradation of cholesterol in hepatocytes. In summary, in this study, we found that ACOT12 deficiency is responsible for the pathogenesis of NAFLD through the accumulation of acetyl-CoA and the stimulation of DNL and cholesterol via activation of PPARα and inhibition of cholesterol trafficking.

scholarly journals Metabolic Regulation of Invadopodia and Invasion by Acetyl-CoA Carboxylase 1 and De novo Lipogenesis

PLoS ONE ◽  
2012 ◽  
Vol 7 (1) ◽  
pp. e29761 ◽  
Author(s):  
Kristen E. N. Scott ◽  
Frances B. Wheeler ◽  
Amanda L. Davis ◽  
Michael J. Thomas ◽  
James M. Ntambi ◽  
...  
Keyword(s):  
Metabolic Regulation ◽  
De Novo ◽  
De Novo Lipogenesis ◽  
Acetyl Coa Carboxylase ◽  
Acetyl Coa

Quantitative analysis of acetoacetate metabolism in AS-30D hepatoma cells with 13C and 14C isotopic techniques

1997 ◽  
Vol 272 (6) ◽  
pp. E945-E951 ◽  
Author(s):  
A. L. Holleran ◽  
G. Fiskum ◽  
J. K. Kelleher
Keyword(s):  
De Novo ◽  
Lipid Synthesis ◽  
Tca Cycle ◽  
Hepatoma Cells ◽  
Dichloroacetic Acid ◽  
De Novo Lipogenesis ◽  
Ratio Method ◽  
Acetyl Coa ◽  
Isotopic Methods ◽  
Host Metabolism

Experimental hepatoma cells utilize acetoacetate as an oxidative energy source and as a precursor for lipid synthesis. The significance of ketone body metabolism in tumors lies in the study of tumor-host metabolism and the ketoneMic condition that is often present in cancer patients. The quantitative importance of acetoacetate and glucose was investigated in AS-30D cells with use of 13C and 14C isotopic methods. In addition, the effects of acetoacetate were compared with those of dichloroacetic acid (DCA), an activator of pyruvate dehydrogenase (PDH). The 14CO2 ratio method evaluated the entry of pyruvate into the tricarboxylic acid (TCA) cycle and revealed that acetoacetate diverted pyruvate from PDH to pyruvate carboxylation. In contrast, DCA increased the oxidation of glucose largely through PDH, indicating that PDH is not maximally active in the absence of DCA. Isotopomer spectral analysis of lipid synthesis demonstrated that, in the absence of acetoacetate, glucose supplied 65% of the acetyl-CoA used for de novo lipogenesis. When 5 mM acetoacetate was included in the incubation, glucose was displaced as a lipogenic precursor and acetoacetate supplied 85% of the acetyl-CoA for lipogenesis vs. only 2% for glucose. Thus AS-30D cells have a large capacity for acetoacetate utilization for de novo lipogenesis.

scholarly journals mTORC2-AKT signaling to ATP-citrate lyase drives brown adipogenesis and de novo lipogenesis

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
C. Martinez Calejman ◽  
S. Trefely ◽  
S. W. Entwisle ◽  
A. Luciano ◽  
S. M. Jung ◽  
...  
Keyword(s):  
De Novo ◽  
Ppar Gamma ◽  
Akt Signaling ◽  
De Novo Lipogenesis ◽  
Atp Citrate Lyase ◽  
Acetyl Coa ◽  
Brown Adipocytes ◽  
Glucose And Lipid Metabolism ◽  
Citrate Lyase ◽  
Acetyl Coa Synthesis

Abstract mTORC2 phosphorylates AKT in a hydrophobic motif site that is a biomarker of insulin sensitivity. In brown adipocytes, mTORC2 regulates glucose and lipid metabolism, however the mechanism has been unclear because downstream AKT signaling appears unaffected by mTORC2 loss. Here, by applying immunoblotting, targeted phosphoproteomics and metabolite profiling, we identify ATP-citrate lyase (ACLY) as a distinctly mTORC2-sensitive AKT substrate in brown preadipocytes. mTORC2 appears dispensable for most other AKT actions examined, indicating a previously unappreciated selectivity in mTORC2-AKT signaling. Rescue experiments suggest brown preadipocytes require the mTORC2/AKT/ACLY pathway to induce PPAR-gamma and establish the epigenetic landscape during differentiation. Evidence in mature brown adipocytes also suggests mTORC2 acts through ACLY to increase carbohydrate response element binding protein (ChREBP) activity, histone acetylation, and gluco-lipogenic gene expression. Substrate utilization studies additionally implicate mTORC2 in promoting acetyl-CoA synthesis from acetate through acetyl-CoA synthetase 2 (ACSS2). These data suggest that a principal mTORC2 action is controlling nuclear-cytoplasmic acetyl-CoA synthesis.

Tartronic acid promotes de novo lipogenesis and inhibits CPT-1β by upregulating acetyl-CoA and malonyl-CoA

Life Sciences ◽  
2020 ◽  
Vol 258 ◽  
pp. 118240
Author(s):  
Xin'e Shi ◽  
Xiaomin Zhou ◽  
Jie Wang ◽  
Deming Zhang ◽  
Kuilong Huang ◽  
...  
Keyword(s):  
De Novo ◽  
De Novo Lipogenesis ◽  
Acetyl Coa ◽  
Malonyl Coa ◽  
Tartronic Acid

scholarly journals mTOR complex-2 stimulates acetyl-CoA and de novo lipogenesis through ATP citrate lyase in HER2/PIK3CA-hyperactive breast cancer

Oncotarget ◽  
2016 ◽  
Vol 7 (18) ◽  
pp. 25224-25240 ◽  
Author(s):  
Yaqing Chen ◽  
Jianchang Qian ◽  
Qun He ◽  
Hui Zhao ◽  
Lourdes Toral-Barza ◽  
...  
Keyword(s):  
Breast Cancer ◽  
De Novo ◽  
De Novo Lipogenesis ◽  
Atp Citrate Lyase ◽  
Acetyl Coa ◽  
Citrate Lyase

scholarly journals Serine catabolism generates NADPH to support hepatic lipogenesis

2021 ◽  
Author(s):  
Zhaoyue Zhang ◽  
Tara TeSlaa ◽  
Xincheng Xu ◽  
Xianfeng Zeng ◽  
Lifeng Yang ◽  
...  
Keyword(s):  
De Novo ◽  
Pentose Phosphate ◽  
De Novo Lipogenesis ◽  
Hepatic Lipogenesis ◽  
Pharmacological Interventions ◽  
Reaction Sequence ◽  
Acetyl Coa ◽  
Serine Pathway ◽  
Fat Synthesis ◽  
Liver Folate

Carbohydrate can be converted into fat by de novo lipogenesis. This process is known to occur in adipose and liver, and its activity is upregulated in fatty liver disease. Chemically, de novo lipogenesis involves polymerization and reduction of acetyl-CoA, using NADPH as the electron donor1. While regulation of the responsible enzymes has been extensively studied, the feedstocks used to generate acetyl-CoA and NADPH remain unclear. Here we show that, while de novo lipogenesis in adipose is supported by glucose and its catabolism via the pentose phosphate pathway to make NADPH, liver makes fat without relying on glucose. Instead, liver derives acetyl-CoA from acetate and lactate, and NADPH from folate-mediated serine catabolism. Such NADPH generation involves the cytosolic serine pathway running in liver in the opposite direction observed in most tissues and tumors, with NADPH made by the SHMT1-MTHFD1-ALDH1L1 reaction sequence. Thus, specifically in liver, folate metabolism is wired to support cytosolic NADPH production for lipogenesis. More generally, while the same enzymes are involved in fat synthesis in liver and adipose, different substrates are utilized, opening the door to tissue-specific pharmacological interventions.

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