Elevated miR-22 is accompanied by reduced CCNA2, FGF21, FGFR1, and PGC1α in human and mouse steatosis livers.
(A) Hepatic miR-22, CCNA2, FGF21, FGFR1, and PGC1α mRNA levels as well as serum FGF21 concentrations in healthy people and patients with fatty liver. Steatosis was graded by a pathologist based on fat content: grade 0 (normal) ≤5%; grade 1 (mild) = 5%∼33%; grade 2 (moderate) = 34%∼66%; grade 3 (severe) ≥67%, n = 8-9 livers per group. Because only 1 patient had a steatosis score >3, the patients with steatosis grade 2 and 3 were grouped together. One-way ANOVA with Tukey’s t test. ∗p <0.05, ∗∗p <0.01, ∗∗∗p <0.001. (B) Relationships between the expression levels of indicated genes and hepatic fat content; (C) Hepatic miR-22, Ccna2, Fgf21, Fgfr1, and Pgc1α mRNA levels as well as serum FGF21 concentrations in CD- or WD-fed male mice after 6 months of WD feeding. n = 8 mice per group. Two-tailed Student’s t test. ∗p <0.05, ∗∗p <0.01, ∗∗∗p <0.001. (D) Liver histology revealed that miR-22 promotes fat deposition in diet- and alcohol-induced fatty liver models. WD-fed mice (3-months old) received adenovirus control, or miR-22 (1×109 PFU, via tail vein, 3 times in 10 days) after 10 weeks of WD feeding. For the alcoholic steatosis model, 3-month-old male mice were fed a Liber DeCarli diet supplemented with and without 5% alcohol for 3 weeks. The mice received adenovirus control or miR-22 (1×109 PFU, via tail vein, 3 times in 10 days). The same diet was given during the interventions. Representative H&E-stained liver sections are presented. Scale bar indicates 100 μm. (E) The expression levels of miR-22, Fgf21, Fgfr1, and Pgc1α mRNA levels in hepatocytes (Hepa) and NPCs of CD- or WD-fed male mice. Data = mean ± SD, n = 4. One-way ANOVA with Tukey’s t test. ∗p <0.05, ∗∗p <0.01, ∗∗∗p <0.001. CD, control diet; NPCs, non-parenchymal cells; PFUs, plaque-forming units; WD, Western diet.