The Effect of Intragastric Administration of Botulinum Toxin Type A on Reducing Adiposity in a Rat Model of Obesity Using Micro-CT and Histological Examinations

Abstract

Background/aims: Botulinum toxin type A (BTX), a long-acting inhibitor of muscular contraction in both striated and smooth muscles, is responsible for gastric motility. The aim of this study was to investigate the effects of an endoscopic intragastric BTX injection on weight loss, body fat accumulation, and gastric emptying time.

Methods: The BTX group consisted of 15 obese rats in which 20 U of BTX were injected into the gastric antrum. The saline group consisted of 15 obese rats injected with 20 U of saline, and the control group included 10 obese rats that did not receive a surgical intervention. The gastric emptying time, biochemical parameters, and body fat volume were evaluated using micro-computed tomography (micro-CT) and histologic evaluations.

Results: The postoperative body weight of the BTX group was significantly lower than those of the other groups (p<0.001) at 6 weeks after the operation. The gastric emptying time (156±54 minutes) was significantly delayed in the BTX group. The BTX group showed significantly lower lipid levels than the other groups. A reduction in body fat volume was observed in the BTX group using micro-CT and histological evaluations.

Conclusions: BTX application to the gastric antrum represents a potentially effective treatment for obesity and may help improve the lipid profile by increasing the gastric emptying time.

Keywords: Botulinum toxins; Endoscopes; Obesity.

Fig. 1

Representative micro-computed tomography images obtained from two animals in the control (A) and botulinum toxin type A (BTX) (B) groups are shown, with the fat-specific threshold applied. Fat tissue is shown in gray.

Fig. 2

Time courses of body weight in the control, saline, and botulinum toxin type A (BTX) groups. *A significant difference at p<0.01 level compared to the saline group; ^†A significant difference p<0.01 level compared to the control group.

Fig. 3

Time courses of food intake in the control, saline, and botulinum toxin type A (BTX) groups.

Fig. 4

Gastric emptying time values of the three groups on surgery day (A), day 15 (B), and day 30 (C) after surgery. BTX, botulinum toxin type A; HFD, high fat diet. *A significant difference p<0.05 level compared to the control group; ^†A significant difference at p<0.05 level compared to the saline group.

Fig. 5

The values of serum lipid parameters in the three groups are shown; high-density lipoprotein (HDL, A), low-density lipoprotein (LDL, B), total cholesterol (C), and triglyceride (D). The botulinum toxin type A (BTX) group showed a significantly lower total cholesterol level (p<0.05) and LDL level (p<0.01) than the control group at 4 weeks after surgery. A significant difference at *p<0.01, ^†p<0.05 level compared to the saline group; A significant difference ^‡p<0.01, ^§p<0.05 level compared to the control group.

Fig. 6

The effect of botulinum toxin type A (BTX) on body fat volume is shown in the micro-computed tomography images; (A) before BTX injection, (B) 28 days after BTX injection, and (C) 46 days after BTX injection. The reductions tended to be maintained until 46 days after surgery. HFD, high fat diet. A significant difference at *p<0.001, ^†p<0.01, ^‡p<0.05 level compared to the saline group; A significant difference ^§p<0.001, ^||p<0.01, ^¶p<0.05 level compared to the control group.

Fig. 7

Effects of botulinum toxin type A (BTX) on reducing epididymal (A) and perinephric fat (B). The weights of the epididymal fat pad and perinephric fat pad were lower in the BTX group than in the other groups. HFD, high fat diet. *A significant difference at p<0.01 level compared to the saline group; A significant difference ^†p<0.01, ^‡p<0.05 level compared to the control group.

Fig. 8

Effects of botulinum toxin type A (BTX) on reducing the hepatic lipid levels. (A) Oil Red O staining in liver tissue sections from the three groups at 6 weeks after surgery. (B) The histopathological scores of fat deposits calculated from the Oil Red O staining were not significantly different among the three groups.