Figure 1.
Sequencing and mapping messages of hepatic mRNA profiling of normal and diabetic mice.
(A) The high-quality clean reads from high-throughput sequencing. Total liver RNA from 9-week-old normal (N) and diabetic (DB) db/db mice was used to prepare the high-throughput sequencing library. (B) The proportions of high-quality clean reads unmapped and/or mapped to unique genes, multiple genes and genome. (C) The number of genes detected in normal and diabetic mouse liver. (D) The top 15 abundance change genes downregulated or upregulated in diabetic mouse liver. (E) The top 15 fold change genes downregulated or upregulated in diabetic mouse liver.
Figure 2.
Genes and the related biological processes altered in diabetic mouse liver.
(A) The 8551 selected genes as described in Figure S1A were separated into two distinct clusters according to the genes upregulated or downregulated in diabetic (DB) mouse liver compared with normal (N) control. Red lines indicate Cluster A including 1933 upregulated genes in diabetic mouse liver. Blue lines indicate Cluster B including 694 downregulated genes . Purple lines indicate the total 2627 altered genes, which include all genes in Cluster A and B. (B) The clustered genes were assigned to different biological processes based on Gene Ontology using the web tool DAVID. The top 10 biological functions and the case genes in each cluster ranked by P-value were listed (case genes ≥ 10).
Table 1.
The associated genes in the top 5 KEGG pathways significantly altered in diabetic mouse liver.
Figure 3.
The expression of enzymes directly participated in fatty acid β-oxidation, synthesis and storage was increased or not significantly changed in diabetic mouse liver.
(A) Schematic of fatty acid metabolism and the expression of enzymes directly participated in fatty acid oxidation, synthesis and storage in diabetic mouse liver. Red color represents the enzyme genes upregulated in diabetic mouse liver with fold change ≥ 1.5 and FDR < 0.001, gray color indicates no significant change, and white color indicates the genes were not detected. (B–C) The mRNA levels of the enzymes directly participated in fatty acid oxidation, synthesis and storage in normal (N) and diabetic (DB) mouse liver. ACS, acetyl-CoA synthesis; CAT, carnitine acyl transferase; CPT, carnitine palmitoyltransferase; ACD, acyl-CoA dehydrogenase; EHHADH, enoyl-CoA-hydratase/3-hydroxyacyl-CoA dehydrogenase; ACAT, acetyl-CoA acetyltransferase; ACL, ATP citrate lyase; ACC, acetyl-CoA carboxylase; FAS, fatty acid synthase; ELOVL6, long-chain elongase; SCD1, stearoyl-CoA desaturase 1; GPAT, mitochondrial glycerol 3-phosphate acyltransferase; DGAT, diacylglycerol acyltransferase.
Figure 4.
The expression of enzymes directly participated in gluconeogenesis, glycolysis and glycogen metabolism was increased or not significantly changed in diabetic mouse liver.
(A, D) Schematic of gluconeogenesis, glycolysis and glycogen metabolism, and the expression of enzymes directly participated in these processes of diabetic mouse liver. The key enzymes include HK, PFK-1 and PK for glycolysis, G6Pase, FBPase and PEPCK for gluconeogenesis, HK, UDP-GP and GS for glycogen synthesis, and GP for glycogenolysis. Red color represents the upregulated genes in diabetic mouse liver with fold change ≥ 1.5 and FDR < 0.001, gray color indicates no significant change, and white color indicates the genes were not detected. (B, C and E) The mRNA levels of the enzymes directly participated in glycolysis, gluconeogenesis and glycogen metabolism in normal (N) and diabetic (DB) mouse liver. HK, hexokinase; PGI, Phosphoglucoisomerase; PFK-1, phosphofructokinase; ALDB, aldolase; TPI, triose phosphate isomerase; GAPDH, Glyceraldehyde 3-phosphate dehydrogenase; PGK, phosphoglycerokinase; PGM, phosphoglyceromutase; PK, pyruvate kinase; LDH, lactate dehydrogenase; PDH, pyruvate dehydrogenase; PC, pyruvate carboxylase; G6Pase, Glucose-6-Phosphatase; FBPase, Fructose 1,6-bisphosphatase; PEPCK, Phosphoenolpyruvate carboxykinase; UDP-GP, Uridine diphosphoglucose pyrophosphorylase; GS, Glycogen Synthase; GP, Glycogen Phosphorylase.
Figure 5.
An overview of the key fatty acid and glucose metabolic gene nodes and their alteration in the 9-week-old diabetic db/db mouse liver.
The gene nodes and their interactions were obtained from literatures, and the alteration of gene expression was from Table S1. Orange arrows indicate the metabolic flux of glucose and fatty acid. Purple arrows indicate the interaction between different metabolic processes and the indicated signaling pathway. Red arrows show that the indicated process and pathway are expected to be upregulated in diabetic mouse liver based on the detected mRNA levels. Red and gray circles labeled on each gene indicate the genes are upregulated and unaffected in diabetic mouse liver respectively. CD36, fatty acid translocase; GLUT2, glucose transporter 2.
Figure 6.
Diabetes is correlated with different liver diseases at a transcriptional view.
(A) The map of top 5 liver diseases enriched with the genes altered in 9-week-old db/db mouse liver. 2627 altered genes were assigned to different diseases using the web tool FunDO. The sizes of the disease nodes are proportional to the number of enriched genes. (B) The number of hit genes and P-value of the top 5 enriched liver diseases in (A).