Effect of vertical sleeve gastrectomy on alcohol consumption and preferences in dietary obese rats and mice: A plausible role for altered ghrelin signaling

Abstract

Vertical sleeve gastrectomy (VSG) and Roux-en-Y gastric bypass (RYGB) are the most common surgical options for the treatment of obesity and metabolic disorder. Whereas RYGB may result in greater and more durable weight loss, recent clinical and pre-clinical studies in rats have raised concerns that RYGB surgery may increase risk for alcohol use disorder (AUD). In contrast, recent clinical reports suggest a lesser risk for AUD following VSG, although no preclinical studies have been done to confirm that. Therefore, the present study sought to determine the effects of VSG on ethanol intake and preferences in rodent models using protocols similar to those previously used in animal studies for RYGB. Male Sprague Dawley rats and male C57B6 mice were made obese on a high fat diet (60%kcal from fat) and received VSG or no surgery (controls). All animals then were given access to increasing concentrations of ethanol (2%, 4%, 6%, and 8%), presented for few days each. Compared to controls, VSG rats consumed significantly less of 2, 6 and 8% ethanol and showed significantly reduced preferences to 6 and 8% ethanol over water. VSG mice also displayed reduced intake and preference for 6 and 8% ethanol solutions. After a two-week period of forced abstinence, 8% ethanol was reintroduced and the VSG rats and mice continued to exhibit reduced consumption and less preference for ethanol. Regarding the underlying mechanism, we hypothesized that the removal of the ghrelin producing part of the stomach in the VSG surgery is a possible contributor to the observed reduced ethanol preference. To test for functional changes at the ghrelin receptors, the VSG and control rats were given IP injections of acyl-ghrelin (2.5nmol and 5nmol) prior to ethanol access. Neither concentration of ghrelin resulted in a significant increase in 8% ethanol consumption of VSG or control subjects. Next, the rats were given IP injections of the ghrelin receptor antagonist, JMV (2.5mg/kg body weight). This dose induced a significant reduction in 8% ethanol consumption in the VSG group, but no effect on ethanol intake in the controls. While ghrelin injection was uninformative, increased sensitivity to subthreshold doses of the ghrelin receptor antagonist may indicate reduced ghrelin signaling following VSG. Overall, these findings suggest that bariatric patients with increased susceptibility to AUD may benefit from receiving VSG instead of RYGB surgery, and that changes in ghrelin signaling, at least in part, may play a role in the differential AUD risks between the two most commonly performed bariatric surgical procedures.

Vertical Sleeve Gastrectomy Attenuates Hedonic Feeding Without Impacting Alcohol Drinking in Rats

“…Our data indicate that VSG reduced intake of alcohol at low concentration and that this phenomenon is diminished as the concentration of alcohol is escalated. These data are in agreement with a recent preclinical study that found reduced alcohol intake after VSG surgery ( 26 ). However, in that study, VSG rats and mice consumed significantly less alcohol at all concentrations tested.…”

Systematic review of olfactory shifts related to obesity

“…In other words, RYGB was more invasive to the vagal innervation of the gastrointestinal tract than SG. Furthermore, these procedural differences between SG and RYGB are found to alter food and alcohol consumption, based on evidence from recent animal studies . Here, we propose that these differences can also explain the differential olfactory outcomes following RYGB and SG.…”

Roux‐en‐Y gastric bypass surgery normalizes dopamine D1, D2, and DAT levels

“…Vertical sleeve gastrectomy is another common surgical option for the treatment of obesity. Rats that underwent this surgery underwent the removal of the ghrelin producing part of the stomach and showed a decreased preference for alcohol than control subjects (Orellana, Jamis, Horvath, & Hajnal, ). There has been other studies comparing different bariatric techniques that found increased drinking in RYGB groups but not gastric banding (Conason et al, ; King et al, ; Suzuki, Haimovici, & Chang, ; Svensson et al, ).…”