title: Continuous carbachol infusion promotes peripheral cell proliferation and mimics vagus hyperactivity in a rat model of hypothalamic obesity.
abstract: Lesions of the ventromedial hypothalamus (VMH) result in obesity and enhanced cellular proliferation in various organs, including the pancreas, gastrointestinal tract, and liver. Previous studies have suggested that vagal hyperactivity, rather than overeating, induces the peripheral cell proliferation in VMH-lesioned rats. The goal of the present study was to investigate the mechanism of peripheral cell proliferation in VMH-lesion-induced obesity by infusing rats with the acetylcholine agonist, carbachol, and then measuring cellular proliferation in the pancreas and duodenum using immunohistochemistry. The ventromedial hypothalamus was bilaterally lesioned in five rats. In other rats, the bilateral vagus nerves were ligated (vagotomized), and saline or carbachol was continuously administered by an osmotic minipump (n = 5 in each group). Three days later, rats were killed, and cell proliferation was assessed in the pancreas and the duodenum using immunohistochemistry for proliferating cell nuclear antigen (PCNA). Additionally, cellular proliferation in the duodenum was more precisely examined by assessing incorporation of 5-bromo-2'-deoxyuridine (BrdU). Cellular proliferation was higher in rats that received carbachol infusions and in rats with VMH-lesions when compared with control rats (P < 0.05, respectively). The pancreatic PCNA-expressing cells were predominantly identified as the B-cells of the islets of Langerhans. These data demonstrate that carbachol infusion can induce pancreatic and duodenal cell proliferation to a degree that was comparable to that in vagal hyperactivity induced by VMH lesions.
authors.affiliation: Department of Applied Biology, Kyoto Institute of Technology, Kyoto, Japan. ryoshimu@kit.ac.jp
authors.forename: Ryoichi
authors.initials: R
authors.lastname: Yoshimura
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Omori
authors.forename: Shingo
authors.initials: S
authors.lastname: Somekawa
authors.forename: Toshimasa
authors.initials: T
authors.lastname: Osaka
authors.forename: Rokuro
authors.initials: R
authors.lastname: Ito
authors.forename: Shuji
authors.initials: S
authors.lastname: Inoue
authors.forename: Yasuhisa
authors.initials: Y
authors.lastname: Endo
mesh_terms: D000818:Animals; D001835:Body Weight; D002217:Carbachol / Q000008:administration & dosage / Q000494:pharmacology; D049109:Cell Proliferation / Q000187:drug effects*; D018679:Cholinergic Agonists / Q000008:administration & dosage / Q000494:pharmacology; D004195:Disease Models, Animal; D004386:Duodenum / Q000166:cytology / Q000378:metabolism; D004435:Eating; D005260:Female; D007031:Hypothalamus / Q000187:drug effects / Q000378:metabolism; D009765:Obesity / Q000378:metabolism*; D010179:Pancreas / Q000166:cytology / Q000378:metabolism; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D014628:Vagotomy; D014630:Vagus Nerve / Q000187:drug effects / Q000502:physiology
chemical_list: D018679:Cholinergic Agonists; D018809:Proliferating Cell Nuclear Antigen; D002217:Carbachol