Vagal innervation of the hepatic portal vein and liver is not necessary for Roux-en-Y gastric bypass surgery-induced hypophagia, weight loss, and hypermetabolism

Abstract

Objective: To determine the role of the common hepatic branch of the abdominal vagus on the beneficial effects of Roux-en-Y gastric bypass (RYGB) on weight loss, food intake, food choice, and energy expenditure in a rat model.

Background: Although changes in gut hormone patterns are the leading candidates in RYGB's effects on appetite, weight loss, and reversal of diabetes, a potential role for afferent signaling through the vagal hepatic branch potentially sensing glucose levels in the hepatic portal vein has recently been suggested in a mouse model of RYGB.

Methods: Male Sprague-Dawley rats underwent either RYGB alone (RYGB; n = 7), RYGB + common hepatic branch vagotomy (RYGB + HV; n = 6), or sham procedure (sham; n = 9). Body weight, body composition, meal patterns, food choice, energy expenditure, and fecal energy loss were monitored up to 3 months after intervention.

Results: Both RYGB and RYGB + HV significantly reduced body weight, adiposity, meal size, and fat preference, and increased satiety, energy expenditure, and respiratory exchange rate compared with sham procedure, and there were no significant differences in these effects between RYGB and RYGB + HV rats.

Conclusions: Integrity of vagal nerve supply to the liver, hepatic portal vein, and the proximal duodenum provided by the common hepatic branch is not necessary for RYGB to reduce food intake and body weight or increase energy expenditure. Specifically, it is unlikely that a hepatic portal vein glucose sensor signaling RYGB-induced increased intestinal gluconeogenesis to the brain depends on vagal afferent fibers.

Fig. 1

Schematic diagram showing the site of common hepatic branch vagotomy. The diagram is a ventral view of the rat abdomen and based on traced vagal branches and blood vessel supply. The neurovascular bundle containing the hepatoesophageal artery (ahe) and the common hepatic branch were slightly lifted by means of a microhook and cauterized with a high temperature micro-cautery device near the gray arrow. The common hepatic branch further divides into fascicles running along the hepatic artery proper and portal vein, to innervate the hepatic hilus region, and the gastroduodenal artery, innervating the proximal duodenum and pancreas. Abbreviations: ahp = common hepatic artery; ac = celiac artery; ags = left gastric artery; agdd = gastroduodenal artery.

Fig. 2

Body weight change (A) and body composition 3 months after surgery (B,C) of rats with Roux-en-Y gastric bypass surgery (RYGB, n = 7, open squares), rats with Roux-en Y gastric bypass surgery plus common hepatic branch vagotomy (RYGB + HV, n = 6, closed circles), sham-operated rats (n = 9, open circles). Bars that do not share the same letters are significantly (p < 0.05) different from each other (based on ANOVA followed by Bonferrroni-adjusted multiple comparisons). The times of measurements of meal patterns, fat preference, energy expenditure, and fecal energy content are indicated by gray bars.

Fig. 3

Food and water intake of sham-operated (white bars, n = 9), RYGB (dark grey bars, n = 7), and RYGB + HV rats (black bars, n = 6). (A) Intake of Ensure for days 3–9 post-surgery. (B) Total calorie intake with choice of Ensure, high-fat diet, and chow, for days 10–22 post-surgery. (C) Water intake measured on 5 consecutive days, five weeks post-surgery, when on 2-choice diet.

Fig. 4

Liquid meal patterns assessed 12–18 days after RYGB (dark grey bars, n = 6), RYGB + HV (black bars, n = 6), and sham-surgery (white bars, n = 8). Average meal size (A), meal frequency (B), intermeal interval (C), meal duration (D), satiety ratio (E), and total intake (F). Bars that do not share the same letters are significantly different from each other (p<0.05), based on two-way ANOVA).

Fig. 5

Food choice and fat preference of RYGB and sham-operated, obese and lean rats. (A) Total calorie intake from chow and high fat diet in two-choice paradigm. (B) Relative fat preference. Bars that do not share the same letters are significantly different from each other (p<0.05), based on two-way ANOVA.

Fig. 6

Energy expenditure (EE) and respiratory exchange rate (RER) measured during three consecutive days, 10 weeks after RYGB (open squares and dark gray bars, n = 6), RYGB + HV (filled circles and black bars, n = 6), or sham surgery (open circles and white bars, n = 8). A, B: Diurnal variation of energy expenditure expressed per lean body mass (A) and RER (B). C–F: Average dark (C,E) and light phase (D,F) energy expenditure and RER over 3 days. Bars that do not share the same letters are significantly different from each other (p<0.05), based on separate one-way ANOVAs followed by Tukey’s multiple comparisons tests.

Fig. 7

Fecal energy content assessed 10 weeks after RYGB (dark grey bars, n = 6), RYGB + HV (black bars, n = 6), and sham-surgery (white bars, n = 8). Bars that do not share the same letters are significantly different from each other (p<0.05), based on one-way ANOVA followed by Tukey’s multiple comparisons tests.