DGAT-1 inhib 
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  • ||||||||||  Journal:  Targeted engineering of camelina and pennycress seeds for ultrahigh accumulation of acetyl-TAG. (Pubmed Central) -  Nov 15, 2024   
    Similar spatial distributions of specific TAG and acetyl-TAG molecular species, as well as their probable diacylglycerol (DAG) precursors, provide additional evidence that acetyl-TAG and TAG are both synthesized from the same tissue-specific DAG pools. Remarkably, this ultrahigh production of acetyl-TAG in transgenic seeds exhibited minimal negative effects on seed properties, highlighting the potential for production of designer oils required for economical biofuel industries.
  • ||||||||||  Venclexta (venetoclax) / Roche, AbbVie
    SLC25A1 Reprograms Mitochondrial and Fatty Acid Metabolism to Promote the Progression of Acute Myeloid Leukemia (Halls G-H (San Diego Convention Center)) -  Nov 6, 2024 - Abstract #ASH2024ASH_5848;    
    We also revealed that a self-protection mechanism after stress by up-regulating phosphoglycerides (PGs) and triglycerides (TAGs) in SLC25A1 KD cells, and the effect could be reversed by inhibiting DGAT1, a key enzyme catalyzing the conversion of fatty acids to TAGs. In conclusion, targeting mitochondrial metabolism and fatty acid metabolism using the SLC25A1 inhibitor might be a potential novel strategy for enhancing AML therapy and overcoming drug resistance.
  • ||||||||||  ML210 / University of Sydney
    Targeting Lipid Droplet Biogenesis to Enhance Ferroptosis in Acute Myeloid Leukemia (Halls G-H (San Diego Convention Center)) -  Nov 6, 2024 - Abstract #ASH2024ASH_5264;    
    We first confirmed that the exogenous supplement of PUFA (Linoleic acid) significantly enhanced ferroptosis in AML cells treated with the GPX4 inhibitor ML210, while monounsaturated fatty acid (MUFA, Oleic acid) suppressed GPX4 inhibition-induced ferroptosis, as expected...These findings suggest a novel therapeutic strategy for AML by targeting lipid metabolism to potentiate ferroptosis. Further investigation into the molecular underpinnings of the synergy, in vivo validations, and the development of specific DGAT inhibitors will be critical for translating these findings into clinical applications.
  • ||||||||||  metformin / Generic mfg.
    DGAT1 Inhibition Enhances Metformin-Induced Ferroptosis in AML By Targeting Lipid Metabolism (Halls G-H (San Diego Convention Center)) -  Nov 6, 2024 - Abstract #ASH2024ASH_5257;    
    We showed that defective metabolic rewiring towards glycolysis, along with increased lipid peroxidation, ROS production, and lipid droplet formation, are mechanisms associated with enhanced metformin sensitivity in AML. Our results highlight the potential of leveraging metabolic vulnerabilities in AML for the development of more effective and personalized therapeutic strategies.
  • ||||||||||  Journal:  Milk traits characterization and association studies with DGAT1 polymorphisms in Bagnolese sheep. (Pubmed Central) -  Nov 1, 2024   
    CT genotype at the SNP g.5553 of DGAT1 has shown a positive association with fat and protein milk yield percentage suggesting it could be considered a marker to improve productions of this breed. Finally, the new genotyping techniques used for this study enable a cheap and reliable characterization of two DGAT1 SNPs in sheep.
  • ||||||||||  Journal:  Effect of gene CRTC2 on the differentiation of subcutaneous precursor adipocytes in goats. (Pubmed Central) -  Nov 1, 2024   
    The results revealed that SiRNA-mediated interference with CRTC2 significantly inhibited its differentiation and suppressed lipid droplet aggregation. So, this study indicates that CRTC2 is a positive regulator that promoting cell differentiation of subcutaneous adipocyte in goats, which lays the foundation for an in-depth study of the role of CRTC2 in lipid deposition in goats.
  • ||||||||||  Biomarker, Journal:  Genotype-Dependent Variations in Oxidative Stress Markers and Bioactive Proteins in Hereford Bulls: Associations with DGAT1, LEP, and SCD1 Genes. (Pubmed Central) -  Oct 26, 2024   
    The SCD1 AA genotype displayed the highest activities of GluRed, GPx, and SOD, indicating a more effective antioxidant defence, while the VA genotype had the highest MDA levels and the VV genotype showed lower MDA levels, suggesting protective effects against oxidative damage. These findings highlight genotype specific variations in the oxidative stress markers and bioactive compound levels, providing insights into the genetic regulation of oxidative stress and antioxidant defences, which could inform breeding strategies for improving oxidative stress resistance in livestock and managing related conditions.
  • ||||||||||  Journal, Epigenetic controller:  DNA methylation analysis to differentiate reference, breed, and parent-of-origin effects in the bovine pangenome era. (Pubmed Central) -  Oct 22, 2024   
    These findings highlight genotype specific variations in the oxidative stress markers and bioactive compound levels, providing insights into the genetic regulation of oxidative stress and antioxidant defences, which could inform breeding strategies for improving oxidative stress resistance in livestock and managing related conditions. This work demonstrates the need to consider reference genome effects to explore genetic and epigenetic differences accurately and identify DMRs involved in controlling certain genes.
  • ||||||||||  Preclinical, Journal:  The effect and mechanism of exposure to polystyrene nanoplastics on lipid metabolism in mice liver (Pubmed Central) -  Oct 21, 2024   
    In vivo and in vitro imaging and in situ cell localization revealed that PS-NPs were mainly enriched in hepatic stellate cells and hepatic Kupffer cells in liver tissue. Exposure to PS-NPs induces disorder of liver lipid metabolism, which may be related to the accumulation of PS-NPs in hepatic stellate cells and hepatic Kupffer cells, providing basis for searching early biomarkers of PS-NPs exposure and further mechanism research.
  • ||||||||||  IDENTIFYING NEUROGENIC MECHANISMS FOR METABOLIC DYSFUNCTION ASSOCIATED STEATOHEPATITIS (MASH) AFTER SPINAL CORD INJURY () -  Oct 15, 2024 - Abstract #AASLD2024AASLD_749;    
    SCI or an obesogenic diet induce MASH but likely through different mechanisms. The independent and combined contribution of neurogenic and obesogenic mechanisms highlight the cross-talk of functional central nervous system circuitry on hepatic metabolic health, which is expected to provide an innovative framework for continued investigation to improve cardiometabolic health of the SCI population and potential new insights for alleviating obesogenic MASH.
  • ||||||||||  Ocaliva (obeticholic acid) / Intercept, Rezdiffra (resmetirom) / Madrigal Pharma
    A NEW THERAPEUTIC APPROACH FOR MASLD/MASH TREATMENT () -  Oct 15, 2024 - Abstract #AASLD2024AASLD_721;    
    Therefore, NTP can be a useful intervention for treating MASLD/MASH. Widely used for over 50 years in Japan and China without significant side effect, NTP can be an effective and safe medication for MASLD/MASH management.
  • ||||||||||  Journal:  Oxysterol binding protein regulates the resolution of TLR-induced cytokine production in macrophages. (Pubmed Central) -  Oct 3, 2024   
    Lipidomic analysis suggested that the effect of Osbp on TLR signaling may be mediated by alterations in triglyceride production and treating cells with a Dgat1 inhibitor, which blocks triglyceride production and completely abrogates the effect of Osbp on TLR signaling. Thus, Osbp is a sterol sensor that transduces perturbations of the lipidome to modulate the resolution of macrophage inflammatory responses.
  • ||||||||||  Journal:  Metabolic engineering-induced transcriptome reprogramming of lipid biosynthesis enhances oil composition in oat. (Pubmed Central) -  Sep 25, 2024   
    Furthermore, there were marked improvements in the total oil content in oat leaves, as well as primary metabolites changes in both oat grains and leaves, while maintaining homeostasis in the transgenic oat plants. These findings underscore the effectiveness of genetic engineering in manipulating oat oil composition and content, offering promising implications for human consumption and animal feeding through oat crop improvement programmes.
  • ||||||||||  Journal:  Obesity facilitated colon cancer progression is mediated by increased diacylglycerol o-acyltransferases 1 and 2 (DGAT1/2) levels. (Pubmed Central) -  Sep 21, 2024   
    These findings underscore the effectiveness of genetic engineering in manipulating oat oil composition and content, offering promising implications for human consumption and animal feeding through oat crop improvement programmes. This is a novel mechanism of DGAT1/2-dependent metabolic and tumorigenic remodeling in obesity-facilitated colon cancer, providing a platform for the future development of effective treatments for colon cancer patients.
  • ||||||||||  Journal:  Maize genotypes with favourable dgat1-2 and fatb alleles possess stable high kernel oil and better fatty acid health and nutritive indices. (Pubmed Central) -  Sep 17, 2024   
    These double-mutants had lower saturated FA (12.2?%), and higher unsaturated FA (87.0?%), indicating reduced susceptibility to autooxidation, with lower atherogenicity (0.14), thrombogenicity (0.27) and peroxidisability (48.15), higher cholesterolaemic index (7.16), optimum oxidability (5.27) and higher nutritive-value-index (3.35) compared to d+d+/f+f+, making them promising for significant health and nutritional benefits. Locally adapted stable novel double-mutants with high-oil and better FA properties identified here can expedite the maize breeding programs, meeting production demands and addressing long-standing challenges for breeders.
  • ||||||||||  Review, Journal:  The role of DGAT1 and DGAT2 in tumor progression via fatty acid metabolism: A comprehensive review. (Pubmed Central) -  Sep 17, 2024   
    This article summarizes the characteristics of tumor fatty acid metabolism and explains how DGAT1 and DGAT2 specifically promote tumor progression. In addition, this review discusses the potential of lipid-lowering drugs in tumor treatment, providing a new perspective on targeting fatty acid metabolism to inhibit tumor progression in the future, while emphasizing the importance of DGAT1 and DGAT2 as potential targets for tumor treatment.
  • ||||||||||  Lipid droplets: a dynamic cell-organelle to combat Alzheimer's disease and aging. (MCP Room N427) -  Aug 22, 2024 - Abstract #Neuroscience2024Neuroscience_2580;    
    plaques upon treatment in the subiculum and cortex regions. These findings suggest that DGAT2-degrader can become a drug candidate to slow down late-stage AD pathology where the clinical markers are very well defined for patient selection.
  • ||||||||||  azithromycin / Generic mfg.
    CODE Brown: A Case of a Novel Variant of a DGAT1 Mutation Causing DIAR7 (Exhibit Hall E) -  Aug 20, 2024 - Abstract #ACG2024ACG_1983;    
    This case identifies a novel DGAT1 variant resulting in DIAR7, contributing to the growing knowledge in identification and treatment of CODEs. While diarrhea remains a common complaint in pediatric patients, it is important to consider rare causes such as CODEs when chronic diarrhea leads to FTT.