Figure 1

Hepatic steatosis and inflammation display circadian rhythmicity during steatohepatitis. (A) WT male mice were fed on a control diet (CD) (n = 3–4 mice per ZT) or a methionine and choline deficient diet (MCDD) (n = 5–6 mice per ZT) for 4 weeks and the blood and liver were sampled around the clock every 6 h. (B) Quantification of hepatic steatosis from H&E stained liver sections (%) and total liver triglyceride contents (mg/g of tissue). (C) Hepatic gene expression of Pnpla2 and Fsp27. (D) quantification of inflammatory foci from the H&E staining of liver tissue section samples. (E) Gene expression of Tnfα and Ccl2. (F) Serum ALT and AST activity (IU/L). (G) Gene expression of Tgfβ, Col1α1 and Timp1. All data are expressed as mean ± SEM. Gene expressions are normalized to B2m and expressed relative to the CD ZT3 level. Rhythmicity of the liver complications and related gene expressions was evaluated by nonlinear regression cosine fitting analysis (cosinor) (Supplementary Table S1). The rhythmicity of each parameter is indicated on their respective graph with the corresponding color. ZT3 values were double-plotted to complete the 24 h cycle. *, rhythmic (p < 0.05), nsr, non-significantly rhythmic, nd, not detected.