The lipogenic enzyme acetoacetyl-CoA synthetase and ketone body utilization for denovo lipid synthesis, a review

Bergstrom, James D.

doi:10.1016/j.jlr.2023.100407

Cited by 16 publications

(5 citation statements)

References 93 publications

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“…AACS has the ability to use ketone bodies for the creation of cholesterol and fatty acids, converting acetoacetate into its CoA ester to generate acetoacetyl-CoA in the cytosol [108]. This process is facilitated by HMGCS, which transforms acetoacetyl-CoA into 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) [109,110]. Subsequently, HMGCRa is able to facilitate the transformation of HMG-CoA into mevalonic acid in order to generate cholesterol [111].…”

Section: Discussionmentioning

confidence: 99%

High Starch Induces Hematological Variations, Metabolic Changes, Oxidative Stress, Inflammatory Responses, and Histopathological Lesions in Largemouth Bass (Micropterus salmoides)

Xie,

Shao,

Zhang

et al. 2024

Metabolites

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This study evaluated effects of high starch (20%) on hematological variations, glucose and lipid metabolism, antioxidant ability, inflammatory responses, and histopathological lesions in largemouth bass. Results showed hepatic crude lipid and triacylglycerol (TAG) contents were notably increased in fish fed high starch. High starch could increase counts of neutrophils, lymphocytes, monocytes, eosinophils, and basophils and serum contents of TAG, TBA, BUN, and LEP (p < 0.05). There were increasing trends in levels of GLUT2, glycolysis, gluconeogenesis, and LDH in fish fed high starch through the AKT/PI3K signal pathway. Meanwhile, high starch not only triggered TAG and cholesterol synthesis, but mediated cholesterol accumulation by reducing ABCG5, ABCG8, and NPC1L1. Significant increases in lipid droplets and vacuolization were also shown in hepatocytes of D3–D7 groups fed high starch. In addition, high starch could decrease levels of mitochondrial Trx2, TrxR2, and Prx3, while increasing ROS contents. Moreover, high starch could notably increase amounts of inflammatory factors (IL-1β, TNF-α, etc.) by activating NLRP3 inflammasome key molecules (GSDME, caspase 1, etc.). In conclusion, high starch could not only induce metabolic disorders via gluconeogenesis and accumulation of glycogen, TAG, and cholesterol, but could disturb redox homeostasis and cause inflammatory responses by activating the NLRP3 inflammasome in largemouth bass.

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Section: Discussionmentioning

confidence: 99%

High Starch Induces Hematological Variations, Metabolic Changes, Oxidative Stress, Inflammatory Responses, and Histopathological Lesions in Largemouth Bass (Micropterus salmoides)

Xie,

Shao,

Zhang

et al. 2024

Metabolites

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“…Acetoacetyl-CoA (AcAc-CoA) synthetase (AACS) (AcAc-CoA ligase, Enzyme Commission no. : 6.2.1.16) is a cytosolic lipogenic enzyme found in many tissues involved in lipid synthesis 35 . AACS is a highly regulated enzyme found in developing brain during myelination 36 , which is essential for neural development 37 .…”

Section: Discussionmentioning

confidence: 99%

“…AACS is a highly regulated enzyme found in developing brain during myelination 36 , which is essential for neural development 37 . Additionally, AACS catalyzes the coupling of acetoacetate (AcAc), one of the ketone bodies (KBs), to CoA to produce cytosolic AcAc-CoA, which is be utilized directly for the synthesis of cytosolic HMG-CoA and then for cholesterol synthesis 35 . From this perspective, AACS' regulation of lipid metabolism is congruent with MSMO1 and occurs upstream of it.…”

Section: Discussionmentioning

confidence: 99%

Identifying MSMO1, ELOVL6, AACS, and CERS2 related to lipid metabolism as biomarkers of Parkinson's disease

Wang,

Zhao,

Chen

et al. 2024

Preprint

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The mechanisms underlying lipid metabolic disorders in Parkinson's diseases (PD) remain unclear. Weighted Gene Co-Expression Network Analysis (WGCNA) was conducted to identify PD-related modular genes and differentially expressed genes (DEGs). Lipid metabolism-related genes (LMRGs) were extracted from Molecular Signatures Database. Candidate genes were assessed with overlapping modular genes, DEGs, and LMRGs for the purpose of building protein-protein interaction(PPI) networks. Then, biomarkers were generated by machine learning and Backpropagation Neural Network development according to candidate genes. Biomarker-based enrichment and network modulation analyses were executed to investigate related signal pathway. Following dimensionality reduction clustering and annotation, scRNA-seq was submitted to cellular interactions and trajectory analysis to analyze regulatory mechanisms of critical cells. Finally, qRT-PCR was conducted to confirm the expression of biomarkers in PD patients. Four biomarkers (MSMO1, ELOVL6, AACS, and CERS2) were obtained and highly predictive after analysis mentioned above. Then, OPC, Oli, and Neu cells were the primary expression sites for biomarkers according to scRNA-seq studies. Finally, we confirmed mRNA of MSMO1, ELOVL6 and AACS were downregulated in PD patients comparing with control, while CERS2 was upregulated. In conclusion, MSMO1, ELOVL6, AACS, and CERS2 related to LMRGs could be new biomarkers for diagnosing and treating PD.

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“…The lower fatty acid oxidation rate on the ketogenic diet caused an imbalance between fatty acid supply (fatty acid delivery and uptake) and demand (oxidation) and a doubling of nonoxidative myocardial fatty acid disposal (Figure 1). In addition, ketones themselves may have contributed to the increase in myocardial lipids through increased lipogenesis [3]. These data demonstrate that a ketogenic diet has potentially adverse cardiac effects because chronically elevated myocardial lipid content can cause cardiac lipotoxicity [4].…”

Section: Figurementioning

confidence: 99%

Ketones with a twist: Tipping the heart's hat to fat

Javaheri,

Mittendorfer

2024

Obesity

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The lipogenic enzyme acetoacetyl-CoA synthetase and ketone body utilization for denovo lipid synthesis, a review

Cited by 16 publications

References 93 publications

High Starch Induces Hematological Variations, Metabolic Changes, Oxidative Stress, Inflammatory Responses, and Histopathological Lesions in Largemouth Bass (Micropterus salmoides)

High Starch Induces Hematological Variations, Metabolic Changes, Oxidative Stress, Inflammatory Responses, and Histopathological Lesions in Largemouth Bass (Micropterus salmoides)

Identifying MSMO1, ELOVL6, AACS, and CERS2 related to lipid metabolism as biomarkers of Parkinson's disease

Ketones with a twist: Tipping the heart's hat to fat

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