Table 1.
Primer sequences and probes used for real-time reverse transcription polymerase chain reaction.
Table 2.
Body and liver weights of the mice.
Table 3.
Biochemical data of serum.
Fig 1.
Photomicrographs of the liver of TSOD mice at the ages of 3 and 9 months.
A-D) In male and female TSOD mice, intralobular and portal inflammation is observed, although hepatic steatosis and ballooning are not conspicuous. Intralobular inflammation tends to be more severe in male mice than in females at 3 months. (H&E staining, original magnification ×200).
Fig 2.
Photomicrographs of the liver of db/db mice at 3 and 9 months.
A-D) In db/db mice, steatosis is conspicuous in both 3- and 9-month-old mice. Intralobular and portal inflammation is milder compared to that in TSOD mice, and ballooning is not conspicuous at both ages. Steatosis is more severe in male mice than females at 3 months. (H&E staining, original magnification ×200).
Table 4.
Histopathological findings.
Fig 3.
Image analysis for quantification of steatosis.
A-E) There is no significant sex difference in the frequency of steatotic area in 3- and 9-month-old TSOD mice (one-tailed t-test for young mice and two-tailed t-test for old mice). F-J) The frequency of steatotic area is significantly higher in 3-month-old male db/db mice than females (one-tailed t-test); however, significant sex differences are not observed at 9 months (two-tailed t-test). (A-D,F-I: Original magnification ×400).
Fig 4.
Image analysis for quantification of fibrosis.
A-J) The frequency of Sirius red-positive fibrotic area is significantly higher in male mice than in female mice in TSOD and db/db mice at the age of 3 months (one-tailed t-test); however, significant sex differences are not observed in both strains at 9 months (two-tailed t-test). (A-D,F-I: Original magnification ×400).
Fig 5.
Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining of liver tissues.
A-D) Positively stained hepatocytes are observed in 3-month-old male (A) and female (B) TSOD mice and 9-month-old male (C) and female (D) db/db mice (original magnification ×400). E) The number of positively stained hepatocytes is significantly higher in 3-month-old male TSOD mice than in females (one-tailed t-test), but there is no significant sex difference in 9-month-old TSOD mice. F) For db/db mice, there is no significant sex difference in both age groups.
Fig 6.
Triglyceride (TG) and total cholesterol (T-Cho) levels in the liver.
A) At 3 months of age, TG levels in the livers of TSOD mice show no significant sex difference; however, at 9 months, they are significantly higher in females than in males (two-tailed t-test). For db/db mice, hepatic TG levels are significantly higher in male mice than in females at 3 and 9 months of age (one-tailed t-test for young mice and two-tailed t-test for old mice). B) T-Cho levels in the livers of male db/db mice are significantly higher than those in females at 3 and 9 months of age (one-tailed t-test for young mice and two-tailed t-test for old mice).
Fig 7.
Hepatic expression levels of genes determined by real-time reverse transcription polymerase chain reaction.
A) The expression levels of fibroblast growth factor (FGF)21 mRNA are significantly higher in female TSOD mice than males at 3 months and significantly higher in female TSOD and db/db mice than males at 9 months (two-tailed t-test). B-D) For the expression levels of myeloid differentiation primary response (MYD)88, peroxisome proliferator-activated receptor (PPAR)α, and PPARγ, significant sex differences are not observed in both strains and age groups (two-tailed t-test).