Journal: bioRxiv

Article Title: Regulation of lipid dysmetabolism and neuroinflammation linked with Alzheimer’s disease through modulation of Dgat2

doi: 10.1101/2025.02.18.638929

Figure Lengend Snippet: a, Flow chart depicting the experimental setup. Each UAS gene was crossed with the region-specific Gal-4 drivers. To explore the contribution of Dgat2 in Aβ42 and App accumulation, we performed Elav-driven Dgat2 KD and Dgat2 OE in Drosophila and used an App NLG-F mouse model with Dgat2 inhibitor . b, Negative geotaxis assay of Elav and GLaz drove A pp NLG and Aβ42 models in 3wk males and females . c-e, Memory assay of Drosophila : Original method, the difference between fly decisions, flies avoiding shock odor in Elav, GLaz and OK107 App NLG and Aβ42 models. Two-way ANOVA with multiple comparisons done with Uncorrected Fisher’s LSD test was performed for geotaxis, n=3 replicates per group and each group had 10 flies. Chi-square tests were performed for memory assay, ( App NLG N=50, Aβ42=46, W 1118 =54, GFP=45 ). *P<0.05, **P<0.01 and ***P<0.001 n.s = not significant. Exact p values are provided in the source data.

Article Snippet: To investigate whether Dgat2 contributes to AD-related phenotypes, we used PF-06424439, a Dgat2 noncompetitive (MedChemExpress, CAS No#1469284-78-3), slowly reversible inhibitor with an IC50 of 14nM.

Techniques:

Journal: bioRxiv

Article Title: Regulation of lipid dysmetabolism and neuroinflammation linked with Alzheimer’s disease through modulation of Dgat2

doi: 10.1101/2025.02.18.638929

Figure Lengend Snippet: a, Negative geotaxis assay of Elav driven Dgat2 KD and OE in AD models in 3wk male and female . b-c, Memory assay of Drosophila: original method, difference between fly decisions, flies avoiding shock odor in Elav driven Dgat2 KD and OE in App NLG and Aβ42 . d-e, Total, day and night sleep (in minutes) and sleep fragmentation in Elav driven Dgat KD and OE in APP/aβ Models. Two-way ANOVA with multiple comparisons done with Uncorrected Fisher’s LSD test was performed for geotaxis, n=3 replicates per group and each group had 10 flies. Chi-square tests were performed for memory assay, (App NLG N=50, Aβ42=46, W 1118 =54, GFP=45). Non-parametric One-way ANOVA with multiple comparisons done with Kruskal Wallis test was performed for sleep activity and sleep fragmentation. Each dot represents several flies *P<0.05, **P<0.01 and ***P<0.001 n.s = not significant. Exact p values are provided in the source data.

Article Snippet: To investigate whether Dgat2 contributes to AD-related phenotypes, we used PF-06424439, a Dgat2 noncompetitive (MedChemExpress, CAS No#1469284-78-3), slowly reversible inhibitor with an IC50 of 14nM.

Techniques: Activity Assay

Journal: bioRxiv

Article Title: Regulation of lipid dysmetabolism and neuroinflammation linked with Alzheimer’s disease through modulation of Dgat2

doi: 10.1101/2025.02.18.638929

Figure Lengend Snippet: a, Representative image showing the expression of lipid accumulation (green), synaptic loss (purple), a marker of neurodegeneration, and DAPI (white) in the brains of Elav-driven KD in AD models in flies . b-c, Quantification of the expression level of lipid counts and synapsin intensity in Elav-driven AD models. d, Relative expression of inflammatory genes. e, Relative expression of metabolic genes in flies. f, Immunofluorescence staining showing the expression level of lipid spots and Gfap in hippocampus region of the brain of WT and App NLG-F mouse model in presence of Dgat2 inhibitor. g, Quantification of the Lipid spot expression level, h, Quantification of the Gfap expression level n=3 mice per group. i, Relative expression level of inflammatory and AD risk genes WT and App knock-in mouse models in the presence of Dgat2 inhibitor. One-way ANOVA with Turkey’s multiple comparisons test was performed for Flies data. N=3 replicates per group and each group has 8-10 flies. Two-way ANOVA with multiple comparisons done with Uncorrected Fisher’s LSD test was performed. *p < .05; **p < .01; ***p < .001; ns = not significant. Exact p values are provided in the source data.

Article Snippet: To investigate whether Dgat2 contributes to AD-related phenotypes, we used PF-06424439, a Dgat2 noncompetitive (MedChemExpress, CAS No#1469284-78-3), slowly reversible inhibitor with an IC50 of 14nM.

Techniques: Expressing, Marker, Immunofluorescence, Staining, Knock-In

Journal: bioRxiv

Article Title: Regulation of lipid dysmetabolism and neuroinflammation linked with Alzheimer’s disease through modulation of Dgat2

doi: 10.1101/2025.02.18.638929

Figure Lengend Snippet: a Relative Dgat2 transcription factors expressions level in Elav-driven App NLG and Aβ42 . b, Total, day and night sleep (minutes) and sleep fragmentation in Elav-driven Dgat2 TFs KD models. c, Representative image showing the expression of lipid accumulation (green), synaptic loss (purple), a marker of neurodegeneration, and DAPI (white) in the brains of Elav-driven Dgat2 TFs KD models . d-e, Quantification of the expression level of lipid counts and synapsin intensity in Elav-driven Dgat2 TFs KD models . f, Relative expressions level of AD risk genes in Elav driven Dgat2 TFs KD models. g-h, Relative expressions level of Dgat2 TFs and AD risk genes in App knock-in mouse model in presence of Dgat2 inhibitors. One-way ANOVA with Turkey’s multiple comparisons test was performed for Flies data. N=3 replicates per group and each group has 8-10 flies. n=3 mice per group. Two-way ANOVA with multiple comparisons done with Uncorrected Fisher’s LSD test was performed in mouse data. *p < .05; **p < .01; ***p < .001; ns = not significant. Exact p values are provided in the source data.

Article Snippet: To investigate whether Dgat2 contributes to AD-related phenotypes, we used PF-06424439, a Dgat2 noncompetitive (MedChemExpress, CAS No#1469284-78-3), slowly reversible inhibitor with an IC50 of 14nM.

Techniques: Expressing, Marker, Knock-In

Journal: bioRxiv

Article Title: Regulation of lipid dysmetabolism and neuroinflammation linked with Alzheimer’s disease through modulation of Dgat2

doi: 10.1101/2025.02.18.638929

Figure Lengend Snippet: Graphical illustration showed the impacts of panneuronal and glial specific expression of App NLG and Aβ42 without and with Dgat2 KD in Drosophila and microglial/ astrocytic activation and lipid accumulation in App NLG-F mouse model. The top panel result shows that panneuronal and glial-specific expression of App NLG and Aβ42 led to compromised locomotor and cognitive performance. It also led to enhanced lipid accumulation and reduced synapsin level, which were further rescued with Dgat2 KD (up and down arrows). The bottom panel shows the changes in Gfap, Ib1, Dgat2 stain, and Adrp protein in young/old and with Dgat2 inhibitors in APP NLG-F mouse model.

Article Snippet: To investigate whether Dgat2 contributes to AD-related phenotypes, we used PF-06424439, a Dgat2 noncompetitive (MedChemExpress, CAS No#1469284-78-3), slowly reversible inhibitor with an IC50 of 14nM.

Techniques: Expressing, Activation Assay, Staining