Botulinum toxin injected in the gastric wall reduces body weight and food intake in rats

Aliment Pharmacol Ther. 2000 Jun;14(6):829-34. doi: 10.1046/j.1365-2036.2000.00765.x.

Abstract

Background: Botulinum toxin is a powerful, long-acting inhibitor of muscular contractions in both voluntary and smooth muscle. It acts by blocking the release of the neurotransmitter acetylcholine. In the stomach, propulsive contractions of the antrum are necessary for the gastric contents to pass into the duodenum.

Aims: To investigate whether intramuscular injections of botulinum toxin type A into the gastric antrum of rats would cause a reduction in food intake and hence body weight, by inhibition of gastric emptying.

Materials and methods: This was a prospective, randomized, 3-way parallel group study in rats. The first group was anaesthetized, laparotomized and given 20 U of botulinum toxin type A by intramuscular injection into the gastric antrum (botulinum toxin type A group, n=14). The second group was anaesthetized, laparotomized and injected with saline (sham group, n=14) and the third group did not have any intervention (control group, n=5). Food intake was measured daily for 7 weeks and body weight was measured daily for 10 weeks.

Results: There was a significant difference in loss of body weight between the two treated groups (14.0 +/- 8.2% botulinum toxin type A group, 4.4 +/- 2.7% sham group; P < 0.001). Further, the time to reach the weight nadir was significantly longer in the botulinum toxin type A group (8.7 +/- 3.9 days) compared with the sham group (5.3 +/- 3.8 days; P < 0.04). There were no significant differences between the sham and control groups for any of the body weight parameters. The minimum dietary intake was significantly lower in the botulinum toxin type A group than in the sham group (37.8 +/- 21.8% of the basal value in the botulinum toxin type A group, vs. 65.5 +/- 32.0 in the sham group, P < 0.05). In addition, the time to reach the nadir was significantly prolonged (8.2 +/- 3.5 days, botulinum toxin type A group vs. 4.9 +/- 1.7 days, sham group, P < 0.001).

Conclusions: The parallel reduction of body weight and food intake in botulinum toxin type A treated animals is consistent with a long lasting inhibition of the antral pump. This is probably due to slowed gastric emptying leading to early satiety. Patients with morbid obesity might benefit from endoscopic injections of botulinum toxin type A into the stomach wall.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Dyskinesia Agents / administration & dosage
  • Anti-Dyskinesia Agents / pharmacology*
  • Body Weight / drug effects
  • Botulinum Toxins / administration & dosage
  • Botulinum Toxins / pharmacology*
  • Eating / drug effects*
  • Gastric Emptying / drug effects*
  • Gastric Emptying / physiology
  • Obesity / therapy
  • Prospective Studies
  • Pyloric Antrum / drug effects*
  • Pyloric Antrum / physiology
  • Random Allocation
  • Rats
  • Rats, Wistar
  • Stomach

Substances

  • Anti-Dyskinesia Agents
  • Botulinum Toxins

Grants and funding