Differential role of vagus nerve in maintaining diurnal gene expression rhythms in the proximal small intestine

Abstract

Background: We have documented previously diurnal rhythms in intestinal sugar transporter expression. We set out to identify the role of the vagus nerve in these rhythms.

Materials and methods: Sprague-Dawley rats underwent truncal vagotomy (V; n = 9) and were pair-fed with sham-operated (n = 4) and unoperated rats (n = 6). Rats were killed at ZT3 and ZT9 (ZT: Zeitgeber time with ZT0 set at lights-on), the time interval over which sucrase, SGLT1, GLUT2, and GLUT5 expression exhibit significant anticipatory increases. Jejunal RNA expression for the four genes were assessed by Northern blot analysis. SGLT1 and GLUT2 expression was further studied by Western blot analysis and in situ hybridization.

Results: Control rats (sham-operated plus unoperated rats) exhibited the expected increase in RNA levels at ZT9 versus ZT3 for SGLT1, GLUT2, GLUT5, and sucrase (P < 0.01 for each). The diurnal rhythm of mRNA levels for GLUT2 and sucrase, but not for SGLT1 or GLUT5, were blunted in V rats. At protein level, SGLT1 was induced 4.3-fold in control rats (P < 0.01) and 3.8-fold in V rats (P < 0.01), whereas GLUT2 was induced 3.3-fold in control rats (P < 0.01) but only 1.4-fold in V rats (N.S.).

Conclusions: Our results indicate that signaling through the vagus nerve is necessary for the anticipatory induction of GLUT2 and sucrase. Persistence of normal rhythms in both SGLT1 and GLUT5 indicates that diurnal induction of these genes is independent of vagal innervation. Entrainment of anticipatory diurnal gene expression in the intestine occurs via two separate pathways that are differentially dependent on vagal input.