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. 2022 Jan 12;130(1):017005. doi: 10.1289/EHP9373

Figure 3.

Figure 3A is a set of two dot plots titled Liver weight and Liver index, plotting Absolute weight (grams), ranging from 0.0 to 2.0 in increments of 0.5 and percentage of body weight, ranging from 0 to 8 in increments of 2 (y-axis) across Wild type and Hep-K O (x-axis) for carboxymethylcellulose and diethylhexyl phthalate, respectively. Figure 3B is a set of six dot plots titled triglyceride, cholesterol, cholinesterase, alkaline phosphatase, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol, plotting concentration (millimolar), ranging from 0.3 to 0.8 in increments of 0.1; concentration (millimolar), ranging from 0 to 4 in unit increments; concentration (millimolar), ranging from 0 to 6 in increments of 2; Activity (units per liter), ranging from 0 to 150 in increments of 50; concentration (millimolar), ranging from 0.0 to 0.6 in increments of 0.2; and concentration (millimolar), ranging from 0.0 to 2.0 in increments of 0.5 (y-axis) across Wild-type Hep-K O (x-axis) for carboxymethylcellulose and diethylhexyl phthalate, respectively. Figure 3C is a bar graph titled Hepatic triglyceride, plotting concentration (micrograms per milligram liver tissue), ranging from 0 to 4 in unit increments (y-axis) across Wild type and Hep-K O (x-axis) for carboxymethylcellulose and diethylhexyl phthalate. Figure 3D is one set of stained tissues displayed two columns, namely, control and diethylhexyl phthalate and two rows, namely, Wild type and Hep-K O. Figure 3E is one set of stained tissues and one bar graph. The stained tissue displays two columns, namely, control and diethylhexyl phthalate for peroxisome proliferator-activated receptor lowercase gamma staining and two rows, namely, Wild type and Hep-K O. A closeup image displays Hepatocytes and Non-hepatocyte cells in control. The bar graph titled Hepatic pathological severity, plotting evaluating score, ranging from 0 to 20 in increments of 5 (y-axis) across Wild type and Hep-K O (x-axis) for carboxymethylcellulose and diethylhexyl phthalate. Figure 3F is one set of stained tissues and two bar graphs. The stained tissue displays two columns, namely, control and diethylhexyl phthalate for Macrophages staining and two rows, namely, Wild type and Hep-K O with a scale bar of 200 micrometers. The two bar graphs titled C L E C 4 F begin superscript positive end superscript Kupffer cells and F 4 by 80 begin superscript positive end superscript Macrophages, plotting cell numbers per site, ranging from 0 to 150 in increments of 50 and 0 to 400 in increments of 100 (y-axis) across Wild type and Hep-K O (x-axis) for carboxymethylcellulose and diethylhexyl phthalate, respectively.

Effect of hepatocyte-specific PPARγ knockout in DEHP-induced fatty liver. Wild-type (WT; n=7/group) and hepatocyte-specific PPARγ knockout (Hep-KO; n=5/group) C57BL/6J male mice were treated with 0.5% (wt/vol) sodium carboxymethylcellulose (CMC; vehicle control) or DEHP (625mg/kg BW) by daily gavage for 28 d. (A) Liver weight and liver index of mice at the end of the treatment. The data are provided in Table S14. (B) Plasma level of triglycerides (TGs), cholesterol (CHO), high-density lipoprotein cholesterol (HDLC), low-density lipoprotein cholesterol (LDLC), alkaline phosphatase (ALP), and cholinesterase (CHE) of WT (n=57/group) and Hep-KO (n=45/group) mice at the end of the treatment. The data are provided in Table S15. (C) Hepatic TG concentration in the liver of WT (n=7/group) and Hep-KO (n=5/group) mice at the end of the treatment. The data are provided in Table S16. (D) Representative histology images (up) and quantification of hepatic steatosis (down) in the WT (n=7/group) and Hep-KO (n=5/group) mice at the end of the treatment. The data are provided in Table S17. (E) Representative immunohistochemistry (IHC) images of PPARγ expression in the liver of WT and Hep-KO mice at the end of the treatment. (F) Immunofluorescence staining of CLEC4F (red) and F4/80 (green) in the mouse liver (left). Cell nuclei were stained with DAPI (blue). Cells with positive stain in the liver sections of WT (n=7/group) and Hep-KO (n=5/group) mice were quantified using the ImageXpress system under 20×magnification. The data are provided in Table S18. All data are expressed as mean±SD. The data were analyzed using one-way ANOVA followed by Bonferroni’s multiple comparisons test. *p<0.05, **p<0.01, ***p<0.001 compared with the vehicle control (CMC). Note: ANOVA, analysis of variance; BW, body weight; CT, control; DAPI, 4′,6-diamidino-2-phenylindole; DEHP, diethylhexyl phthalate; Hep-KO, hepatic PPAR knockout mice; Mac-KO, macrophage-specific PPAR knockout mice; PPAR, peroxisome proliferator-activated receptor; SD, standard deviation.