Vagal innervation of intestine contributes to weight loss After Roux-en-Y gastric bypass surgery in rats

Abstract

Background: It is conceivable that overstimulation of chemo- and mechano-sensors in the Roux and common limbs by uncontrolled influx of undigested nutrients after Roux-en-Y gastric bypass surgery (RYGB) could lead to exaggerated satiety signaling via vagal afferents and contribute to body weight loss. Because previous clinical and preclinical studies using vagotomy came to different conclusions, the aim was to examine the effects of selective and histologically verified celiac branch vagotomy on reduced food intake and body weight loss induced by RYGB.

Methods: Male Sprague-Dawley rats underwent either RYGB + celiac branch vagotomy (RYGB/VgX, n=15), RYGB + sham celiac branch vagotomy (RYGB/Sham VgX; n=6), Sham RYGB + celiac branch vagotomy (Sham/VgX; n=6), or sham RYGB + sham celiac branch vagotomy (Sham/Sham; n=6), and body weight, body composition, and food choice were monitored for 3 months after intervention.

Results: In rats with RYGB, histologically confirmed celiac branch vagotomy significantly moderated weight loss during the first 40 days after surgery, compared to either sham or failed vagotomy (P<0.05). In contrast, celiac branch vagotomy slightly, but non-significantly, reduced body weight gain in sham RYGB rats compared to sham/sham rats. Furthermore, the significant food intake suppression during the first 32 days after RYGB (P<0.05) was also moderated in rats with verified celiac branch vagotomy.

Conclusions: The results suggest that signals carried by vagal afferents from the mid and lower intestines contribute to the early RYGB-induced body weight loss and reduction of food intake.

Fig. 1

Effect of RYGB with or without celiac branch vagotomy on body weight and composition in rats on a two-choice high (45%) and low (10%) fat diet. Body weight (A), fat mass (B), and lean mass (C) of rats with Roux-en Y gastric bypass surgery plus celiac branch vagotomy (RYGB/VgX, n = 6, closed circles), RYGB plus sham or failed vagotomy (RYGB/Sham VgX, n = 15, open circles), sham operation plus celiac branch vagotomy (Sham/VgX, n = 6, closed squares), and sham operation plus sham vagotomy (Sham/Sham VgX, n = 6, open squares). * p < 0.05, RYGB/VgX vs. RYGB/Sham VgX. ^# p < 0.05, RYGB/VgX vs. Sham/VgX and RYGB/Sham VgX vs. Sham/Sham VgX.

Fig. 2

Effect of RYGB with or without celiac branch vagotomy on daily (A) and cumulative (B) food intake. A two-choice diet consisting of high-fat (45%) and low-fat (10%, regular chow was available throughout the experiment and intake of both diets was measured daily). Mean ± SEM of total calorie intake from both diets is shown. A: ^{^} p <0.05, significant suppression of food intake in RYGB/Sham VgX vs. Sham/Sham VgX; ^# p < 0.05, significantly higher food intake in both RYGB and sham-operated rats with VgX vs. Sham VgX. * p < 0.05, significant interaction between RYGB and VgX, indicating VgX-induced increase in food intake in RYGB rats, but suppression of food intake in sham-operated rats. B: Bars that do not share the same letters are significantly different from each other, p < 0.05.

Fig. 3

Effect of RYGB with or without celiac branch vagotomy in rats on preference for high-fat food. A two-choice diet consisting of high-fat (45%) and low-fat (10%, regular chow was available throughout the experiment and intake of both diets was measured daily. Note that after RYGB but not sham operation, rats progressively reduced preference for the high-fat diet. Mean ± SEM of relative preference for the high-fat diet is shown. * p <0.05 vs. Sham/Sham VgX.

Fig. 4

Effect of RYGB with or without celiac branch vagotomy in rats on fecal output. Mean ± SEM of wet (A) and dry (B) daily fecal output measured 40 days post-surgery is shown. Note that RYGB, but not VgX, had a significant effect on both wet and dry fecal matter. Bars that do not share the same letters are significantly different from each other, p < 0.05.

Fig. 5

Verification of celiac branch vagotomies using the IP Fluorogold retrograde tracing technique [25]. Photomicrographs of representative frontal sections of the caudal brainstem showing retrogradely labeled vagal motor neurons (black) in the dorsal motor nucleus. Note the absence of retrogradely labeled neurons in the lateral pole (lateral to boken white line) of the dorsal motor nucleus in successfully celiac branch vagotomized rats (B,D) but not in sham and failed vagotomies (A,C). Means ± SEM (n = 3–10) of retrogradely labeled (intact) average cells per section in left and right lateral celiac branch columns is shown for each group.