Figure 2. Selective PKCλ/ι Deficiency in Hepatocytes Results in Metabolic Reprogramming.

(A) Top 5 GSEA results of Prkci^f/f;Alb-Cre vs Prkci^f/f livers (n = 3) using compilation H and C5 (MSigDb).

(B-E) GSEA of the indicated genesets.

(F) qPCR of FAO/OXPHOS-related genes in Prkci^f/f (n = 6) and Prkci^f/f;Alb-Cre (n = 8) livers.

(G and H) Plasma ketone body (G) and hepatic triacylglycerol (H) in Prkci^f/f and Prkci^f/f;Alb-Cre mice (n = 8) after 12 h fasting followed by 2 h of refeeding.

(I and J) OCR in primary hepatocytes isolated from Prkci^f/f and Prkci^f/f;Alb-Cre mice (n = 5).

(K) Upstream Regulator Analysis by IPA in Prkci^f/f;Alb-Cre livers vs Prkci^f/f livers (n = 3).

(L) NextBio analysis of gene overlap between genes upregulated in Prkci^f/f;Alb-Cre livers vs Prkci^f/f livers (n = 3, Bioset1, Bs1) and PPARα binding gene set (Biogroup 1, Bg1).

(M and N) Images of DHE assay in Prkci^f/f and Prkci^f/f;Alb-Cre livers (M) and positive area quantification (N) (n = 4). Scale bar, 100 μm.

(O) NextBio analysis of gene overlap between genes upregulated in Prkci^f/f;Alb-Cre livers vs Prkci^f/f livers (n = 3, Bioset1, Bs1) and NRF2 binding gene set (Biogroup 1, Bg1).

(P and Q) NQO1 IHC (P) and immunoblot (Q) in Prkci^f/f and Prkci^f/f;Alb-Cre livers. Scale bar, 100 μm.

(R) qPCR of NRF2 target genes in Prkci^f/f (n = 6) and Prkci^f/f;Alb-Cre (n = 8) livers.

(S) Nfe2l2 expression levels (RNA-seq, FPKM) in Prkci^f/f (n = 3 for chow diet and DEN/HFD) and Prkci^f/f;Alb-Cre (n = 3 and n = 4 for chow and DEN/HFD, respectively) livers.

(T) Immunoblots of indicated proteins in sgPrkci or sgC cells.

(U and V) IF images left) and design of the NRF2 reporter (right) (U). Scale bar, 10 μm. Quantification of NRF2 activity (n > 10 cells) (V).

Mean ± SEM. *p < 0.05, **p < 0.01, ***p < 0.001. See also Figure S3.