Fig. 6: The 12-h clock links membrane fluidity to the rate-limiting metabolic processes in fatty acid monounsaturated and phospholipid remodeling pathways.
From: XBP1 links the 12-hour clock to NAFLD and regulation of membrane fluidity and lipid homeostasis
a The schematic diagram of the fatty acid monounsaturated and phospholipid remodeling pathways. The key enzymes SCD1, LPCAT3, and LCAT are shown. b The ratio of palmitoleate (16:1) to palmitate (16:0) (upper panel) and oleate (18:1) to stearate (lower panel) in total liver lipid extracts are shown (n = 4 per group). c Metabolomic analysis of the relative abundance of the PC species in the indicated mouse livers at 15- and 30 weeks of age (n = 4 per group). d–f 12-h gene oscillations of Scd1 (d), Lpcat3 (e), and Lcat (f) plotted against circadian time (CT) from 2-h resolution transcriptome profiling of the Xbp1flx/flx (blue lines) and AlbCre;Xbp1flx/flx (red lines) mice (n = 2 per timepoint). The respective superimposed 12-h rhythmic eigenvalue/pencil parameters of each gene are shown in the lower panels. g–i ChIP-Seq binding enrichment of XBP1s at gene loci of Scd1, chr19:44,388,626-44,388,882 (g), Lpcat3, chr6:124,679,113-124,679,428 (h), and Lcat, chr8:10,594,301-105,943,367 (i) in Xbp1flx/flx at CT0 (left) and CT8 (middle), and in the AlbCre;Xbp1flx/flx mice (right) (n = 3 per group). The y axis represents the average signal in a 5-bp bin (normalized to 500 bp uniquely mapped reads). Unpaired Student’s t-test analysis was performed with p value indicated. Data are graphed as the mean ± SEM. *p < 0.05, **p < 0.005, ***p < 0.001, ****p < 0.0001.
