Journal: Nature Communications

Article Title: Hepatocyte-specific IL11 cis-signaling drives lipotoxicity and underlies the transition from NAFLD to NASH

doi: 10.1038/s41467-020-20303-z

Figure Lengend Snippet: a Schematic of WDF feeding in mice with hepatocyte-specific expression of sgp130 for data shown in ( b – p ). Three weeks following AAV8-Alb-Null or AAV8-Alb-sgp130 virus injection, mice were fed WDF for 16 weeks. b Western blots showing hepatic levels of sgp130, IL11, IL6, and GAPDH as internal control ( n = 4 mice/group). c Serum IL11 levels. d Serum IL6 levels. e Representative gross anatomy, H&E-stained (scale bars, 50 µm), and Masson’s Trichrome (scale bars, 100 µm) images of livers. Representative dataset from n = 8 mice/group is shown for gross anatomy; representative dataset from n = 4 mice/group is shown for H&E-stained and Masson’s Trichrome images. f Liver weight. g Hepatic triglycerides content. h Serum ALT levels. i Serum AST levels. j Hepatic collagen levels. k Fasting blood glucose levels. l Serum triglycerides levels. m Serum cholesterol levels. n Hepatic GSH content. o Hepatic pro-inflammatory and fibrotic genes expression heatmap (values are shown in Supplementary Fig. and e). p Western blots of hepatic phospho-ERK, ERK, phospho-JNK, JNK, phospho-STAT3, and STAT3 ( n = 4 mice/group). c , d , f – o n = 8 mice/group. c , d , f – n Data are shown as box-and-whisker with median (middle line), 25th–75th percentiles (box), and min–max values (whiskers); one-way ANOVA with Tukey’s correction. Source data are provided as a Source data file.

Article Snippet: Six- to eight-week-old male C57BL/6N mice (InVivos) were injected with 4 × 10 11 gc AAV8-Alb- sgp130 virus to induce hepatocyte-specific expression of soluble gp130; control mice were injected with 4 × 10 11 gc AAV8-Alb-Null virus.

Techniques: Expressing, Injection, Western Blot, Staining, Whisker Assay

Journal: Nature Communications

Article Title: Hepatocyte-specific IL11 cis-signaling drives lipotoxicity and underlies the transition from NAFLD to NASH

doi: 10.1038/s41467-020-20303-z

Figure Lengend Snippet: a Schematic of HFMCD feeding regimen for AAV8-Alb-Cre injected Il11ra1 loxP/loxP (conditional knockout; CKO) mice for experiments shown in ( b – k ). Il11ra1 loxP/loxP mice were intravenously injected with either AAV8-Alb-Null or AAV8-Alb-Cre to delete Il11ra1 specifically in hepatocytes 3 weeks prior to the start of HFMCD diet. b Western blots of hepatic IL11RA and GAPDH ( n = 3 mice/group). c Body weight (shown as a percentage (%) of initial body weight). d Representative gross anatomy, H&E-stained (scale bars, 50 µm), and Masson’s Trichrome (scale bars, 100 µm) images of livers. Representative dataset from n = 5 mice/group is shown for gross anatomy; representative dataset from n = 4 mice/group is shown for H&E-stained and Masson’s Trichrome images. e Hepatic triglycerides content. f Serum ALT levels. g Serum AST levels. h Hepatic GSH content. i Hepatic collagen levels. j Heatmap showing hepatic mRNA expression of pro-inflammatory markers ( Tnfα , Ccl2 , Ccl5 ) and fibrotic markers ( Col1a1, Col1a2, Col3a1, Acta2) . Values are shown in Supplementary Fig. and d. k Western blots showing hepatic ERK and JNK activation status ( n = 3 mice/group). c , e – j NCD ( n = 5 mice/group), HFMCD ( n = 6 mice/group). c Data are shown as mean ± SD, two-way ANOVA with Tukey’s correction, statistical significance ( P values) are shown for comparison between WT HFMCD and CKO HFMCD; e – i data are shown as box-and-whisker with median (middle line), 25th–75th percentiles (box), and min–max values (whiskers); two-way ANOVA with Tukey’s correction. Source data are provided as a Source data file.

Article Snippet: Six- to eight-week-old male C57BL/6N mice (InVivos) were injected with 4 × 10 11 gc AAV8-Alb- sgp130 virus to induce hepatocyte-specific expression of soluble gp130; control mice were injected with 4 × 10 11 gc AAV8-Alb-Null virus.

Techniques: Injection, Knock-Out, Western Blot, Staining, Expressing, Activation Assay, Whisker Assay

Journal: Nature Communications

Article Title: Hepatocyte-specific IL11 cis-signaling drives lipotoxicity and underlies the transition from NAFLD to NASH

doi: 10.1038/s41467-020-20303-z

Figure Lengend Snippet: a Schematic of WDF-fed control and CKO mice for data shown in ( b – m ). Three weeks following AAV8-Alb-Null or AAV8-Alb-Cre virus injection, CKO mice were fed WDF for 16 weeks. b Western blots showing hepatic levels of IL11RA and GAPDH ( n = 3 mice/group). c Body weight (shown as a percentage (%) of initial body weight). d Fat mass. e Representative gross anatomy, H&E-stained (scale bars, 50 µm), and Masson’s Trichrome (scale bars, 100 µm) images of livers. Representative dataset from n = 5/group is shown for gross anatomy; representative dataset from n = 4 mice/group is shown for H&E-stained and Masson’s Trichrome images. f Hepatic triglycerides content. g Liver weight. h Serum ALT levels. i Serum AST levels. j Hepatic GSH content. k Hepatic collagen levels. l Hepatic pro-inflammatory and fibrotic genes expression on heatmap (values are shown in Supplementary Fig. and d). m Western blots showing activation status of hepatic ERK and JNK ( n = 3 mice/group). c , d , f – l n = 5 mice/group. c , d Data are shown as mean ± SD, two-way ANOVA with Tukey’s correction, statistical significance ( P values) are shown for comparison between WT WDF and CKO WDF; f – k data are shown as box-and-whisker with median (middle line), 25th–75th percentiles (box), and min–max values (whiskers); two-way ANOVA with Tukey’s correction. Source data are provided as a Source data file.

Article Snippet: Six- to eight-week-old male C57BL/6N mice (InVivos) were injected with 4 × 10 11 gc AAV8-Alb- sgp130 virus to induce hepatocyte-specific expression of soluble gp130; control mice were injected with 4 × 10 11 gc AAV8-Alb-Null virus.

Techniques: Injection, Western Blot, Staining, Expressing, Activation Assay, Whisker Assay

Journal: Nature Communications

Article Title: Hepatocyte-specific IL11 cis-signaling drives lipotoxicity and underlies the transition from NAFLD to NASH

doi: 10.1038/s41467-020-20303-z

Figure Lengend Snippet: a Schematic showing WDF feeding regimen of Il11ra1 +/+ (WT) and Il11ra1 −/− (KO) mice for experiments shown in ( b – n ). AAV8-Alb-Null, AAV8-Alb-mbIl11ra1 (full-length membrane-bound Il11ra1), and AAV8-Alb-sIl11ra1 (soluble form of Il11ra1)-injected KO mice were given 16 weeks of WDF feeding, three weeks following virus administration. b Western blots showing hepatic levels of IL11RA and GAPDH ( n = 2 mice/group). c Representative gross anatomy, H&E-stained (scale bars, 50 µm) and Masson’s Trichrome (scale bars, 100 µm) images of livers. Representative dataset from n = 6 mice/group is shown for gross anatomy; representative dataset from n = 4 mice/group is shown for H&E-stained and Masson’s Trichrome images. d Liver weight. e Hepatic triglycerides content. f Serum ALT levels. g Serum AST levels. h Hepatic GSH content. i Hepatic collagen content. j Hepatic pro-inflammatory and fibrotic genes expression heatmap (values are shown in Supplementary Fig. and d). k Western blots showing activation status of hepatic ERK and JNK ( n = 2 mice/group). l Fasting blood glucose levels. m Serum triglycerides levels. n Serum cholesterol levels. d – j , l – n n = 6 mice/group. d – i , l – n Data are shown as box-and-whisker with median (middle line), 25th–75th percentiles (box), and min–max values (whiskers); one-way ANOVA with Tukey’s correction. Source data are provided as a Source data file.

Article Snippet: Six- to eight-week-old male C57BL/6N mice (InVivos) were injected with 4 × 10 11 gc AAV8-Alb- sgp130 virus to induce hepatocyte-specific expression of soluble gp130; control mice were injected with 4 × 10 11 gc AAV8-Alb-Null virus.

Techniques: Injection, Western Blot, Staining, Expressing, Activation Assay, Whisker Assay

Journal: Frontiers in Physiology

Article Title: Hepatic SIRT3 Upregulation in Response to Chronic Alcohol Consumption Contributes to Alcoholic Liver Disease in Mice

doi: 10.3389/fphys.2019.01042

Figure Lengend Snippet: Chronic alcohol exposure is associated with upregulated liver SIRT3 expression. Male C57BL/6 mice were fed a control and ethanol-containing Lieber-DeCarli diet. PF, pair feeding; AF, alcohol feeding. All values are denoted as means ± SD Data ( n = 8). (A) Real time PCR analysis of SIRT3 gene expression in liver of mice. (B) Protein expression of SIRT3 in the liver of mice as indicated by Western Blotting. Bars with different characters (a, b) differ significantly, p < 0.05.

Article Snippet: Recombinant AAV8 vectors target mouse SIRT3 (NM_022433.2) under the control of albumin promoter (a liver-specific promoter) were generated by Cyagen Biosciences Inc. (Guangzhou, China).

Techniques: Expressing, Control, Real-time Polymerase Chain Reaction, Gene Expression, Western Blot

Journal: Frontiers in Physiology

Article Title: Hepatic SIRT3 Upregulation in Response to Chronic Alcohol Consumption Contributes to Alcoholic Liver Disease in Mice

doi: 10.3389/fphys.2019.01042

Figure Lengend Snippet: Liver-specific SIRT3 knockdown protects against alcoholic liver disease. Male C57BL/6 mice were fed a control and ethanol-containing Lieber-DeCarli diet. Total cellular lysates from liver tissues ( n = 8) were subjected to immunoblotting assay for SIRT3. PF, pair feeding; AF, alcohol feeding mice were infected AAV8-control virus; AF + SIRT3 KD: alcohol-fed mice were infected with liver specific AAV8-SIRT3 KD. (A) SIRT3 protein expression in mice livers. (B) SIRT3 protein expression in mice hearts. (C) SIRT3 protein expression in mice muscles. (D) Plasma alanine aminotransferase (ALT) levels. (E) Plasma Aspartate aminotransferase (AST) levels. (F) Hepatic triglyceride (TG) contents. (G) Hepatic cholesterol (TC) contents. (H) H&E staining and Oil Red of liver tissues. Bars mean 100 μm. (I) Liver/body weight ratio. (J) Plasma triglyceride (TG) contents. (K) Plasma free fatty acids (FFA) contents. (L) Plasma glycerol contents. Data are expressed as the mean ± SD ( n = 8 mice per group). Bars with different letters (a, b, c) differ significantly ( p < 0.05).

Article Snippet: Recombinant AAV8 vectors target mouse SIRT3 (NM_022433.2) under the control of albumin promoter (a liver-specific promoter) were generated by Cyagen Biosciences Inc. (Guangzhou, China).

Techniques: Knockdown, Control, Western Blot, Infection, Virus, Expressing, Muscles, Clinical Proteomics, Staining

Journal: Frontiers in Physiology

Article Title: Hepatic SIRT3 Upregulation in Response to Chronic Alcohol Consumption Contributes to Alcoholic Liver Disease in Mice

doi: 10.3389/fphys.2019.01042

Figure Lengend Snippet: SIRT3 negatively regulates autophagy in hepatocytes. (A) LC3B and SIRT3 expressions were detected in liver specific SIRT3 KD and AF mice liver, respectively ( n = 8). Quantification of LC3B and SIRT3 expression in liver. (B) HepG2 cells were transfected with siSIRT3 or scramble siRNA and treated with or without CQ (20 μm) for 12 h. Immunoblotting assay for SIRT3 and LC3B. Quantification of LC3B and SIRT3 expression in HepG2 cells. (C) HepG2 cells were co-transfected with recombinant adenovirus GFP-LC3 and siSIRT3 or scramble siRNA with or without CQ (20 μM) for 12 h. The total number of green puncta was counted. Bars mean 25 μm. AF, alcohol feeding mice were infected AAV8-control virus; AF + SIRT3 KD, alcohol-fed mice were infected liver specific AAV-SIRT3 KD. All values are denoted as mean ± SD from three or more independent batches of cells. Bars with different letters (a, b, c, d) differ significantly ( p < 0.05).

Article Snippet: Recombinant AAV8 vectors target mouse SIRT3 (NM_022433.2) under the control of albumin promoter (a liver-specific promoter) were generated by Cyagen Biosciences Inc. (Guangzhou, China).

Techniques: Expressing, Transfection, Western Blot, Recombinant, Infection, Control, Virus

Journal: Frontiers in Physiology

Article Title: Hepatic SIRT3 Upregulation in Response to Chronic Alcohol Consumption Contributes to Alcoholic Liver Disease in Mice

doi: 10.3389/fphys.2019.01042

Figure Lengend Snippet: Autophagy inducer protects against alcoholic liver disease. (A) Autophagy inducer prevents Ethanol induced LDH release from AML12 cells. AML12 cells are treated with Rapamycin (100 nm) for 2 h before Ethanol (300 mM) addition. (B) Inhibition of autophagy promotes Ethanol induced LDH release from AML12 cells. AML12 cells are treated with CQ (20 μM) for 2 h before Ethanol (300 mM) addition. LDH release is measured 12 h later. (C) Autophagy inducer prevents apoptosis in ethanol-treated cells. AML12 cells were induced with Ethanol (300 mM) and treated with or without Rapamycin (100 nm) for 12 h. Immunoblotting assay for Bax, Bcl2 and LC3B. Quantification of Bax, Bcl2 and LC3B expression in AML12 cells. (D) Inhibition of autophagy promotes apoptosis in ethanol-treated cells. AML12 cells were induced with Ethanol (300 mM) and treated with or without CQ (20 μm) for 12 h. Immunoblotting assay for Bax, Bcl2 and LC3B. Quantification of Bax, Bcl2 and LC3B expression in AML12 cells. (E) AML12 cells were transfected with recombinant adenovirus GFP-LC3 and followed by CQ (20 μm) treatment for 2 h before Ethanol (300 mM) addition for 12 h. Total number of green puncta was counted. Bars mean 25 μm. (F) AML12 cells were transfected with siSIRT3 or scramble siRNA, induced with Ethanol (300 mM), and treated with or without CQ (20 μm) for 12 h. Immunoblotting assay for Bax, Bcl2, SIRT3, and LC3B. Quantification of Bax, Bcl2, LC3B, and SIRT3 expression in AML12 cells. All values are denoted as the mean ± SD from three or more independent studies. Bars with different letters (a, b, c, d) differ significantly ( p < 0.05).

Article Snippet: Recombinant AAV8 vectors target mouse SIRT3 (NM_022433.2) under the control of albumin promoter (a liver-specific promoter) were generated by Cyagen Biosciences Inc. (Guangzhou, China).

Techniques: Inhibition, Western Blot, Expressing, Transfection, Recombinant

Journal: bioRxiv

Article Title: Antisense oligonucleotides against monoacylglycerol acyltransferase 1 ( Mogat1 ) improve glucose metabolism independently of Mogat1

doi: 10.1101/2020.08.05.238535

Figure Lengend Snippet: Constitutive liver-specific Mogat1 deletion does not improve insulin sensitivity in mice. Male Mogat1 fl/fl mice and littermate Mogat1 fl/fl albumin Cre+ mice were fed a LFD or a HFD starting at eight weeks of age for 16 weeks. Mice were fasted for 4 hours prior to sacrifice and tissue collection. A: HFD increased bodyweight in both groups. B,C: HFD fed mice have impaired glucose and insulin tolerance compare to LFD groups. D-G: Mogat1 gene expression is reduced in knockout liver and primary hepatocytes without significant compensation of Mogat2. H,I: HFD increased liver weight and TAG content in both genotypes. J: MGAT activity was not affected by diet or genotype. Data are expressed as means ± S.E.M. # p < 0.05 gene effect, † p < 0.05 diet effect; n = 5-10 for mouse studies, n = 3-5 female mice for primary hepatocyte isolations.

Article Snippet: For hepatic Mogat1 overexpression, eight-week-old male C57BL6/J mice were given LFD or HFD for six weeks, then administered AAV8-TBG-eGFP or AAV8-TBG-mouse- Mogat1 by retro-orbital injection (Vector Biolabs, VB1743, custom refseq# BC106135).

Techniques: Gene Expression, Knock-Out, Activity Assay

Journal: bioRxiv

Article Title: Antisense oligonucleotides against monoacylglycerol acyltransferase 1 ( Mogat1 ) improve glucose metabolism independently of Mogat1

doi: 10.1101/2020.08.05.238535

Figure Lengend Snippet: Acute liver-specific deletion of Mogat1 does not improve glucose or insulin tolerance in HFD fed mice. Male Mogat1 fl/fl mice were fed a HFD starting at eight weeks of age. After 16 weeks mice were given a retro-orbital injection of AAV8-TBG-eGFP or Cre recombinase (2 x 10 11 GC per mouse) and remained on diet for an additional 3 weeks. Mice were fasted for 4 hours prior to sacrifice and tissue collection. A: Mogat1 knockdown did not affect body weight. B,C: Acute liver-specific knockout did not improve glucose or insulin tolerance. D: Mogat1 knockout reduced Mogat1 expression without increasing Mogat2 expression in liver. E-F: Liver weights and TAG content were not difference among groups. G: Hepatic MGAT activity was not reduced by acute Mogat1 knockdown in liver. Data are expressed as means ± S.E.M. # p < 0.05 gene effect; n = 9.

Article Snippet: For hepatic Mogat1 overexpression, eight-week-old male C57BL6/J mice were given LFD or HFD for six weeks, then administered AAV8-TBG-eGFP or AAV8-TBG-mouse- Mogat1 by retro-orbital injection (Vector Biolabs, VB1743, custom refseq# BC106135).

Techniques: Injection, Knockdown, Knock-Out, Expressing, Activity Assay

Journal: bioRxiv

Article Title: Antisense oligonucleotides against monoacylglycerol acyltransferase 1 ( Mogat1 ) improve glucose metabolism independently of Mogat1

doi: 10.1101/2020.08.05.238535

Figure Lengend Snippet: Whole-body deletion of Mogat1 causes weight gain and insulin intolerance on a HFD. Male wild-type (WT) and littermate Mogat1 whole body knockout (MOKO) mice were fed a LFD or a HFD starting at eight weeks of age for 16 weeks. Mice were fasted for 4 hours prior to sacrifice and tissue collection. A: Mogat1 knockout mice gain more weight on a HFD than littermate WT controls. B: ECHO MRI indicates MOKO mice have increased whole body mass, while the heterozygous mice had an intermediate phenotype compared to WT controls. C: Glucose tolerance (dosed on lean mass) was not significantly change in MOKO mice. D,E: HFD fed MOKO mice had significantly impaired insulin tolerance and plasma insulin levels compared to WT controls. F: Mogat1 gene expression was not detectable in MOKO mice. G,H: Liver weight but not TAG was increased in MOKO mice fed a HFD compared to LFD controls. I: MGAT activity was unaffected by either diet or genotype. Data are expressed as means ± S.E.M. # p < 0.05 gene effect, † p < 0.05 diet effect; n = 6-7.

Article Snippet: For hepatic Mogat1 overexpression, eight-week-old male C57BL6/J mice were given LFD or HFD for six weeks, then administered AAV8-TBG-eGFP or AAV8-TBG-mouse- Mogat1 by retro-orbital injection (Vector Biolabs, VB1743, custom refseq# BC106135).

Techniques: Knock-Out, Clinical Proteomics, Gene Expression, Activity Assay

Journal: bioRxiv

Article Title: Antisense oligonucleotides against monoacylglycerol acyltransferase 1 ( Mogat1 ) improve glucose metabolism independently of Mogat1

doi: 10.1101/2020.08.05.238535

Figure Lengend Snippet: Hepatic Mogat1 overexpression increases liver TAG and MGAT activity in mice fed a LFD. Male C57BL6/J mice were fed LFD or a HFD starting at eight weeks of age. After 6 weeks of diet mice were injected (retro-orbitally) with AAV8-TGB-eGFP- or AAV8-TGB-Mogat1 (2 x 10 11 GC per mouse) and remained on diet for an additional 10 weeks. Mice were fasted for 4 hours prior to sacrifice and tissue collection. A: HFD fed mice gained weight compare to LFD fed mice in both treatment groups. B,C: Mogat1 overexpression did not impair glucose or insulin tolerance. D-F: Mogat1 and GFP gene expression was significantly increased in AAV8-Mogat1 and AAV8-GFP treated mice, respectively without a change in Mogat2 gene expression. G: Liver weight was unaffected by any treatment. H,I: AAV8-Mogat1 overexpression increased both liver TAG and MGAT activity in LFD mice. J: Western blot analysis indicated Mogat1 and eGFP protein increased in membrane fractions of AAV8 treated livers. Data are expressed as means ± S.E.M. # p < 0.05 gene effect, † p < 0.05 diet effect; n = 8-10.

Article Snippet: For hepatic Mogat1 overexpression, eight-week-old male C57BL6/J mice were given LFD or HFD for six weeks, then administered AAV8-TBG-eGFP or AAV8-TBG-mouse- Mogat1 by retro-orbital injection (Vector Biolabs, VB1743, custom refseq# BC106135).

Techniques: Over Expression, Activity Assay, Injection, Gene Expression, Western Blot, Membrane

Journal: bioRxiv

Article Title: Antisense oligonucleotides against monoacylglycerol acyltransferase 1 ( Mogat1 ) improve glucose metabolism independently of Mogat1

doi: 10.1101/2020.08.05.238535

Figure Lengend Snippet: shRNA mediated Mogat1 knockdown did not improve glucose or insulin tolerance on a HFD. Male C57Bl/6J mice were fed a 10% LFD or a 60% HFD starting at eight weeks of age. After 16 weeks of diet mice were injected (retro-orbitally) with AAV8-U6-shRNA Scramble or shRNAs targeted against Mogat1 (2 x 10 11 GC per mouse) and remained on diet for an additional three weeks. Mice were fasted for 4 hours prior to sacrifice and tissue collection. A: HFD fed mice gained weight compare to LFD Scramble treated controls. B,C: HFD fed mice had impaired glucose and insulin tolerance compared to LFD Scramble control treated mice. D,E: Liver weight and TAG were increased by the HFD but unaffected by Mogat1 shRNA treatment. F,G: Mogat1 ShRNA treatment reduced Mogat1 expression but did not affect Mogat2 expression. Data are expressed as means ± S.E.M. # p < 0.05 from HFD shRNA Scramble control mice, † P < 0.05 from LFD shRNA Scramble controls; n = 7-10.

Article Snippet: For hepatic Mogat1 overexpression, eight-week-old male C57BL6/J mice were given LFD or HFD for six weeks, then administered AAV8-TBG-eGFP or AAV8-TBG-mouse- Mogat1 by retro-orbital injection (Vector Biolabs, VB1743, custom refseq# BC106135).

Techniques: shRNA, Knockdown, Injection, Control, Expressing, Mouse Assay

Journal: bioRxiv

Article Title: Antisense oligonucleotides against monoacylglycerol acyltransferase 1 ( Mogat1 ) improve glucose metabolism independently of Mogat1

doi: 10.1101/2020.08.05.238535

Figure Lengend Snippet: Mogat1 antisense oligonucleotide (ASO, sequence 1) treatment improves insulin sensitivity in HFD fed mice. Male C57Bl/6J mice were fed a LFD or a HFD starting at eight weeks of age. After 16 weeks of diet, mice were injected (intraperitoneally) twice weekly with ASOs targeted against Mogat1 or scramble control (25 mg/Kg) for three weeks. Mice were fasted for 4 hours prior to sacrifice and tissue collection. A: HFD fed mice gained more weight compare to LFD fed controls. B,C: Control ASO treated mice had significantly higher blood glucose and plasma insulin than LFD Control ASO treated mice and HFD Mogat1 ASO treated mice. D: Mogat1 ASO treatment significantly reduced hepatic expression of Mogat1, but not Mogat2 as measured by RT-qPCR. E: Mogat1 ASO treatment increased liver weight (%BW) on HFD. F: Liver triglycerides (TAG) were measured enzymatically and were increased by the HFD. G: Hepatic gene expression of Gpase, Pepck, and Pygl were reduced in the HFD Mogat1 ASO treated mice. H: Glycogen was extracted and measure enzymatically and increased in HFD Mogat1 ASO treated mice. Data are expressed as means ± S.E.M. # p < 0.05 ASO effect, † p < 0.05 diet effect; n = 7-10.

Article Snippet: For hepatic Mogat1 overexpression, eight-week-old male C57BL6/J mice were given LFD or HFD for six weeks, then administered AAV8-TBG-eGFP or AAV8-TBG-mouse- Mogat1 by retro-orbital injection (Vector Biolabs, VB1743, custom refseq# BC106135).

Techniques: Sequencing, Injection, Control, Clinical Proteomics, Expressing, Quantitative RT-PCR, Gene Expression

Journal: bioRxiv

Article Title: Antisense oligonucleotides against monoacylglycerol acyltransferase 1 ( Mogat1 ) improve glucose metabolism independently of Mogat1

doi: 10.1101/2020.08.05.238535

Figure Lengend Snippet: Mogat1 ASO treatment improves glucose tolerance in whole-body Mogat1 null mice on a HFD. Male wild-type (WT) and littermate Mogat1 whole body knockout (MOKO) mice were fed a HFD starting at eight weeks of age. After 16 weeks of diet, mice were injected (intraperitoneally) twice weekly with ASOs targeted against Mogat1 or scramble control (25 mg/Kg) for three weeks. Mice were fasted for 4 hours prior to sacrifice and tissue collection. A,B: Mogat1 ASO treatment improves glucose tolerance despite Mogat1 expression. C,D: Mogat1 ASO treatment causes hepatomegaly and increases liver TAG in wild-type mice on HFD. E: Mogat1 gene expression was reduced by ASO treatment and nearly absent in MOKO livers. F-I: Gene expression markers of interferon signaling are increased in Mogat1 ASO treated MOKO mice on HFD. Data are expressed as means ± S.E.M. # p < 0.05 from Scramble ASO † p < 0.05 from WT controls; n = 5-7.

Article Snippet: For hepatic Mogat1 overexpression, eight-week-old male C57BL6/J mice were given LFD or HFD for six weeks, then administered AAV8-TBG-eGFP or AAV8-TBG-mouse- Mogat1 by retro-orbital injection (Vector Biolabs, VB1743, custom refseq# BC106135).

Techniques: Knock-Out, Injection, Control, Expressing, Gene Expression, Allele-specific Oligonucleotide

Journal: bioRxiv

Article Title: Antisense oligonucleotides against monoacylglycerol acyltransferase 1 ( Mogat1 ) improve glucose metabolism independently of Mogat1

doi: 10.1101/2020.08.05.238535

Figure Lengend Snippet: Type I interferon receptor (INFR-1) neutralizing antibody prevents inflammation without effecting glucose tolerance in mice fed a HFD. Male C57BL/6J mice were fed a HFD starting at eight weeks of age. After 16 weeks of diet, mice were injected (intraperitoneally) twice weekly with ASOs targeted against Mogat1 (sequence 2) or scramble control (25 mg/Kg) with an INFR-1 neutralizing antibody (INFR-Ab) or IgG control (250 ug per mouse twice a week for weeks 1&2, and 500 ug per mouse 3 times for week 3). Mice were fasted for 4 hours prior to sacrifice and tissue collection. A,B: Mogat1 ASO treatment improves glucose tolerance despite INFR-1 antibody treatment. C,D: Liver weight and TAG were unaffected by any treatment E: Liver Mogat1 gene expression was reduced by Mogat1 ASO treatment compared to controls. F-I: Liver gene expression markers of interferon signaling are increased in Mogat1 ASO treated mice and inhibited by INFR-Ab. J: Epididymal Mogat1 gene expression was decreased by Mogat1 ASO treatment. K-N: Epididymal gene expression markers of interferon signaling are inhibited by INFR-Ab. O-Q: Expression of adipose beiging genes were increased by Mogat1 ASO and inhibited by INFR-Ab treatment. Data are expressed as means ± S.E.M. # p < 0.05 from Scramble ASO † p < 0.05 from IgG controls; n = 5.

Article Snippet: For hepatic Mogat1 overexpression, eight-week-old male C57BL6/J mice were given LFD or HFD for six weeks, then administered AAV8-TBG-eGFP or AAV8-TBG-mouse- Mogat1 by retro-orbital injection (Vector Biolabs, VB1743, custom refseq# BC106135).

Techniques: Injection, Sequencing, Control, Gene Expression, Expressing, Allele-specific Oligonucleotide