Ventromedial hypothalamus lesions induce jejunal epithelial cell hyperplasia through an increase in gene expression of cyclooxygenase

Abstract

BACKGROUND:We demonstrated that ventromedial hypothalamus (VMH) lesions facilitate DNA synthesis, which reflects cell proliferation in abdominal organs, including the liver, pancreas, stomach, small intestine and large intestine, all of which are amply innervated by the vagal nerve. OBJECTIVE: To investigate which area DNA synthesis facilitates and what factors contribute to cell proliferation in the small intestine in VMH-lesioned rats. DESIGN: At 7 days after VMH lesions or sham operations, a segment of rat jejunum was taken for histological examination. A part of the jejunum was also removed from VMH-lesioned and sham-operated rats after 3 days and examined for 5-bromo-2 0 -deoxyuridine (BrdU) incorporation. At 6, 12 and 24 h after VMH lesions, the proximal intestine was removed from individual rats, from the pylorus to the mid-jejunum. Total RNA was extracted from these tissues of each rat, and the levels of epidermal growth factor (EGF) and transforming growth factor (TGF)-a mRNA were determined using reverse-transcription polymerase chain reaction. Cyclooxygenase (COX)-1 and -2 mRNA levels were determined using Northern blotting. RESULTS: Jejunal villi in VMH-lesioned rats were markedly enlarged compared to those of sham-operated rats and jejunal crypts in VMH-lesioned rats more markedly incorporated BrdU. Northern blot analysis revealed an increase in COX-1 mRNA after 6, 12 and 24 h in the jejunum of VMH-lesioned rats. COX-2 mRNA was decreased 6 and 12 h after VMH lesioning; however, it was significantly increased 24 h after VMH lesions in comparison to sham-operated rats. The levels of EGF and TGF-a mRNA were unchanged in VMH lesioned rats. CONCLUSION: VMH lesions induced enlargement of jejunal villi and increased the gene expression of COX-1 in the small intestine. Prostaglandins, probably E 2 , induced by COX-1 may be one candidate factor responsible for the cell proliferation of the small intestinal epithelium in these rats.

Continuous carbachol infusion promotes peripheral cell proliferation and mimics vagus hyperactivity in a rat model of hypothalamic obesity

“…4), which is consistent with results from previous studies of the digestive tract (26). It is likely that enhanced proliferation of the epithelial cells in the duodenal crypts results in duodenal villi elongation.…”

Effects of Gastric Vagotomy on Visceral Cell Proliferation Induced by Ventromedial Hypothalamic Lesions: Role of Vagal Hyperactivity

“…Therefore, these effects may be involved in the resistance to ethanol-induced AGML in VMH-lesioned rats. On the other hand, we previously observed an increase in the gene expression of COX-1 and COX-2 in the jejunum of VMH-lesioned rats (Kageyama et al 2003), which should have the stimulatory effect on cell proliferation. Consequently, it is likely that these factors together contribute to the manifestation of resistance to ethanolinduced AGML.…”

“…To date, we have shown that both COX-1 and -2, but not EGF or TGF-α mRNA levels, are increased in the jejunal epithelial cells of VMH-lesioned rats (Kageyama et al 2003). Further study is required to identify what molecules contribute to the cell proliferation process in the gastric mucosa of these animals.…”

Nutrient-induced intestinal adaption and its effect in obesity

“…Animal models of obesity have been able to reveal similar findings and have shown additional cellular differences. After a brain lesion to the ventromedial nucleus of the hypothalamus (VMH) in laboratory rats, a method that produces obesity, intestinal cell hyperplasia and greater villi length occurs compared with the sham-lesion, lean animals 5 . Obese mouse models also show an increase in intestinal absorption 6 and permeability 7 .…”