BATF relieves hepatic steatosis by inhibiting PD1 and promoting energy metabolism
- Institute of Digestive Disease, Guangxi Academy of Medical Sciences, the People's Hospital of Guangxi Zhuang Autonomous Region, China
- College of Animal Science and Technology, Guangxi University, China
- School of Pharmacy, Mongolian National University of Medical Sciences, Mongolia
Figures
Figure 1 with 1 supplement
Effects of BATF on lipid deposition in hepatocytes under high-fat diet.
(A) The mice and liver Oil red O staining in normal diet group (CN) and high-fat diet group (HFD). Bar, 1 cm (left panel) and 100 μm (right panel). (B) The protein expression of BATF in liver …
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Figure 1—source data 1
Effects of BATF on lipid deposition in hepatocytes under high-fat diet.
- https://cdn.elifesciences.org/articles/88521/elife-88521-fig1-data1-v1.zip
Figure 1—figure supplement 1
Effects of BATF on lipid levels in hepatocytes.
(A) Triglyceride content with OA/PA (n=3). (B) BATF mRNA levels. NC, negative control group; siBATF, BATF inhibition group, (n=3). (C) Triglyceride content with OA/PA treatment, (n=5). (D) …
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Figure 1—figure supplement 1—source data 1
Effects of BATF on lipid levels in hepatocytes.
- https://cdn.elifesciences.org/articles/88521/elife-88521-fig1-figsupp1-data1-v1.zip
Figure 2 with 1 supplement
Effects of BATF on hepatic fat deposition in mice.
(A) Experimental designs illustration of mice. (B) Expression of BATF protein in liver (n=4). (C) Densitometric quantification of the blotting. (D) Expression of BATF protein in various tissues of …
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Figure 2—source data 1
Effects of BATF on hepatic fat deposition in mice.
- https://cdn.elifesciences.org/articles/88521/elife-88521-fig2-data1-v1.zip
Figure 2—figure supplement 1
The effect of BATF on metabolic indicators in mice.
(A) Average daily feed intake (n=7). (B) Liver total cholesterol levels (n=8–10). (C) Fasting blood glucose level in mice (n=8–10). (D) Liver glucose oxidase activity. (E) Glucose tolerance test and …
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Figure 2—figure supplement 1—source data 1
The effect of BATF on metabolic indicators in mice.
- https://cdn.elifesciences.org/articles/88521/elife-88521-fig2-figsupp1-data1-v1.zip
Figure 3
BATF boosts lipid breakdown and energy metabolism in mice livers.
(A) ALT activity in mice liver (n=8). (B) AST activity in mice liver (n=7). (C) The Fasn, Srebp1, Gpam, Acc1 mRNA expression level in mice liver (n=6–8). (D) The AMPKα1, Aco, Acox1, Bcl2, Cpt1, Hsl, …
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Figure 3—source data 1
BATF boosts lipid breakdown and energy metabolism in mice livers.
- https://cdn.elifesciences.org/articles/88521/elife-88521-fig3-data1-v1.zip
Figure 4
BATF alleviates HFD-induced adipocyte hypertrophy in mice.
(A) CT images of fat axial view. (B) eWAT of mice. Bar, 1 cm. (C) eWAT weight / bodyweight (n=9–10). (D) iWAT of mice. Bar, 1 cm. (E) eWAT weight / bodyweight (n=9–10). (F) HE staining of eWAT, (G) …
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Figure 4—source data 1
BATF alleviates HFD-induced adipocyte hypertrophy in mice.
- https://cdn.elifesciences.org/articles/88521/elife-88521-fig4-data1-v1.zip
Figure 5
BATF alleviates hepatocyte lipid accumulation by inhibiting PD1.
(A) The mRNA expression of PD1 in liver tissues (n=3). (B) The mRNA expression of PD1 in HepG2 cells (n=3). (C) Oil red O staining of HepG2 cells, Bar, 20 μm, (n=3). (D), (E), (F) Triglyceride …
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Figure 5—source data 1
BATF alleviates hepatocyte lipid accumulation by inhibiting PD1.
- https://cdn.elifesciences.org/articles/88521/elife-88521-fig5-data1-v1.zip
Figure 6
Effects of PD1 antibody on liver lipid metabolism in HFD mice.
(A) Mice bodyweight (n≥5). (B) The mice were injected with IgG or PD1 antibody under HFD (n≥5). (C) Mice fat ratio (n≥5). (D) eWAT of mice. Bar, 1 cm. (E) eWAT weight / bodyweight (n≥5). (F) iWAT of …
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Figure 6—source data 1
Effects of PD1 antibody on liver lipid metabolism in HFD mice.
- https://cdn.elifesciences.org/articles/88521/elife-88521-fig6-data1-v1.zip
Author response image 1
The expression level of BATF in clumster of cells in the liver.
Author response image 2
The images of the heart and spleen of mice.
Tables
Key resources table
| Reagent type (species) or resource | Designation | Source or reference | Identifiers | Additional information |
|---|---|---|---|---|
| Gene (Mice) | BATF | GenBank | NM_016767.2 | |
| Strain, strain background (Mus musculus) | C57BL/6 J (Wild type) | Guangxi Medical University | male | |
| Cell line (Human) | HepG2 (hepatocellular carcinoma, youth) | ATCC | ATCC number: HB-8065 | |
| Cell line (Human) | L02 (Normal, fetal liver) | YUCHI Biology | ||
| Cell line (Mus musculus) | Hepa1-6 (Hepatoma) | ATCC | ATCC number: CRL-1830 | |
| Cell line (Mus musculus) | AML12 (Normal, 3-month-old) | ATCC | ATCC number: CRL-2254 | |
| Cell line (Human) | HEK293T (Normal, Kidney) | ATCC | ATCC number: ACS-4500 | |
| Cell line (Mus musculus) | 3T3L1 (Embryo) | ATCC | ATCC number: CL-173 | |
| Transfected construct (Mus musculus) | HBAAV/8-ZsGreen | packaged by HANBIO | ||
| Transfected construct (Mus musculus) | HBAAV2/8-CMV-m-BATF-3×flag-ZsGreen | packaged by HANBIO | Adeno-associated virus construct to transfect and express the BATF. | |
| Biological sample (Mus musculus) | primary hepatocytes | This paper | Materials and methods: Primary hepatocyte isolation and AAV infection | Freshly isolated from C57BL/6 J |
| Antibody | BATF (D7C5) (Rabbit monoclonal) | Cell signaling technology | Cat# 8638 | WB (1:1000) |
| Antibody | Anti-beta Actin (Rabbit polyclonal) | Servicebio | Cat# GB11001 | WB (1:1000) |
| Antibody | Peroxidase AffiniPure Goat Anti-Rabbit IgG (H+L) (Rabbit Polyclonal) | Jackson ImmunoResearch | Cat# 111-035-003 | WB (1:2000) |
| Recombinant DNA reagent | pcDNA3.1(-)-Mice BATF | This paper | Cell culture and transfection | |
| Recombinant DNA reagent | pcDNA3.1(-)-Mice PD1 | This paper | Cell culture and transfection | |
| Recombinant DNA reagent | pMSCV-PIG-BATF | This paper | Retroviral transduction | |
| Recombinant DNA reagent | pUMVC | Add gene | Plasmid #8449 | |
| Recombinant DNA reagent | pCMV-VSV-G | Add gene | Plasmid # 8454 | |
| Recombinant DNA reagent | pGL3-PD1 vector | This paper | Luciferase assay for promoter activity analysis | |
| Recombinant DNA reagent | pRL-TK | Beyotime Biotechnology | D2760 | |
| Sequence-based reagent | siRNA: BATF RNAi | synthesized from Sangon Biotech | ||
| Commercial assay or kit | Triglyceride assay kit | Nanjing Jiancheng Bioengineering Institute | Cat# A110-1-1 | |
| Commercial assay or kit | Total cholesterol | Nanjing Jiancheng Bioengineering Institute | Cat# A111-1-1 | |
| Commercial assay or kit | Tissue SCAD assay kit | Gen Med | Cat# GMS 50119.2.1 | |
| Commercial assay or kit | Alanine transaminase (ALT) | Nanjing Jiancheng Bioengineering Institute | Cat# C009-2-1 | |
| Commercial assay or kit | Aspartate aminotransferase (AST) | Nanjing Jiancheng Bioengineering Institute | Cat# C010-2-1 | |
| Commercial assay or kit | Cellular ATP content | Beyotime Biotechnology | Cat# S0026 | |
| Commercial assay or kit | RNA Reverse Transcription System | Promega | Cat# A3500 | |
| Commercial assay or kit | ClonExpress II One Step Cloning Kit | Vazyme | Cat# C112-01/02 | |
| Commercial assay or kit | Dual-Lumi II Luciferase Reporter gene Assay kit | Beyotime Biotechnology | Cat# PG089S | |
| Commercial assay or kit | Cellular ATP content | Beyotime Biotechnology | Cat# S0026 | |
| Chemical compound, drug | High-fat-diet (HFD) | Trophic Animal Feed High-tech Co. Ltd | TP2330055M | standar: D12492 |
| Chemical compound, drug | Normal diet (ND) | Trophic Animal Feed High-tech Co. Ltd | TP2330055MC | standar: AIN93 |
| Chemical compound, drug | Oleic acid (OA) | Sigma-Aldrich | Cat# O1383 | |
| Chemical compound, drug | Palmitic acid (PA) | Sigma-Aldrich | Cat# P0500 | |
| Software, algorithm | Image J | National Institutes of Health | https://Imagej.nih.gov/ij/ | |
| Software, algorithm | Adobe Photoshop CS6 | Adobe | https://www.adobe.com/cn | |
| Software, algorithm | GraphPad Prism 8.0.1 | GraphPad | https://www.graphpad.com/ | |
| Other | InVivoPlus anti-mouse PD1 (CD279) (Mouse RMP1-14) | Bio X Cell | Cat# BP0146 | Intraperitoneal injection: 200 μg/mouse |
| Other | Rat IgG-Isotype Control (Rat monoclonal) | abcam | Cat# ab37361 | Intraperitoneal injection: 200 μg/mouse |
