Metabolic Context Regulates Distinct Hypothalamic Transcriptional Responses to Antiaging Interventions
Figure 3
Differences in hypothalamic gene expression and pathway recruitment between C57Bl/6 and db/db mice under ad libitum, sedentary conditions. (a) Graph of Z-ratios showing that differences in gene expression between C57Bl/6 and db/db mice are primarily attributable to transcriptional upregulation, as opposed to down-regulation. Abbreviations: Eif3s1, eukaryotic translation initiation factor 3, subunit J; Ccdc94, coiled-coil domain containing 94; Dhx9, DEAH (Asp-Glu-Ala-His) box polypeptide 9; Enpp5, ectonucleotide pyrophosphatase/phosphodiesterase 5; Bat5, HLA-B associated transcript 5; Tomm22, translocase of outer mitochondrial membrane 22. (b) Pathways that differ between wild-type and db/db mice under ad libitum, sedentary conditions. Aplp2, amyloid beta (A4) precursor-like protein 2; App, amyloid beta precursor protein; Abcb4, ATP-binding cassette, subfamily B member 4; Mt3, metallothionein 3; Nr1h3, nuclear receptor subfamily 1, group H, member 3; Grm7, glutamate receptor, metabotropic 7; Cdkn1b, cyclin-dependent kinase inhibitor 1B. (c) Pias2 and Slc17a6 expression in C57Bl/6 and db/db mice under ad libitum, sedentary conditions. Arrowheads indicate the hypothalamic nuclei, which were traced over the rostrocaudal extent of the hypothalamus to generate an average index of gene expression that would be directly comparable to the microarray analysis conducted in whole-hypothalamus RNA extracts. Pias2, protein inhibitor of activated STAT 2; Slc17a6, solute carrier family 17 member 6. (d) Graph showing densitometric results of the expression analysis. Consistent with the microarray results, both Pias2 and Slc17a6 were significantly upregulated in the hypothalamus of db/db mice. Asterisk (*) indicates statistical significance at following bidirectional student’s -tests. (e) Further validation through semiquantitative PCR reveals that, as shown by the microarray, Gpx7 mRNA is increased and Tomm22 mRNA is reduced in the hypothalamus of db/db mice.
