The relationship between weight loss and cognitive function in bariatric surgery.

BACKGROUND: Previously, we reported short-term improvements in auditory attention, oromotor processing speed, and executive function during the active weight loss phase following bariatric surgery that persisted out to 3 months. In this study, our aims were to investigate the relationship between weight loss and cognitive performance in these patients 1 year following vertical sleeve gastrectomy (VSG) and Roux-en Y gastric bypass (RYGB) surgery and to determine whether preoperative cognitive performance predicted weight loss. METHODS: Adult women ages 18-55 approved for bariatric surgery completed a cognitive battery prior to and at 2, 12, 24, and 52 weeks following VSG (N = 17) or RYGB (N = 18). Scores from each task were assigned to one of the following cognitive domains: auditory attention, processing speed, memory, and executive functioning. Weight loss and cognitive scores for each domain were calculated and compared between cohorts. RESULTS: RYGB surgery resulted in greater weight loss at 1-year follow-up relative to VSG. Both VSG and RYGB procedures resulted in improved performance on different measures of auditory attention and both surgery groups improved across all processing speed tasks. Within the executive function domain, both groups showed improvements, but only the RYGB procedure resulted in improved performance in the Trail Making Test. Baseline auditory attention and memory performance predicted weight loss at 1 year following RYGB but not VSG surgery. Controlling for baseline cognitive performance, percent total weight loss predicted auditory attention at 1 year following RYGB but not VSG surgery. CONCLUSIONS: Bariatric surgery type may result in selective improvements in cognition during the first year following surgery. Presurgical cognitive performance as well as surgery type appears to influence weight loss outcomes.

Investigating relationships between post-prandial gut hormone responses and taste liking ratings prior to and following bariatric surgery: a pilot study.

BACKGROUND: Alterations in gut hormone secretion and reported changes in taste preferences have been suggested to contribute to the weight-reducing effects of bariatric surgery. However, a link between changes in gut hormone secretion and taste preferences following bariatric surgery has yet to be elucidated. METHODS: Here we examined the potential relationships between gut hormone responses (GLP-1 and PYY3-36 peak, ghrelin trough) to a test meal of Ensure and liking ratings for taste mixtures varying in sugar and fat content before and following bariatric surgery (vertical sleeve gastrectomy (VSG): N = 4; Roux-en Y gastric bypass (RYGB): N = 8). RESULTS: Significant increases in GLP-1 and PYY3-36 peak and a significant drop in ghrelin trough were observed following surgery. Pre- and postoperation, patients with higher postprandial GLP-1 or PYY3-36 peaks gave lower liking ratings for mixtures containing a combination of fat and sugar (half and half + 20% added sugar) whereas, for the combined surgery analyses, no relationships were found with solutions comprised of high fat (half and half + 0% sugar), predominantly high sugar (skim milk + 20% added sugar), or low fat and low sugar (skim milk + 0% added sugar). Within the RYGB patients, patients with the greatest increase in postprandial GLP-1 peak from preoperation to postoperation also demonstrated the greatest decrease in liking for half & half + 20% added sugar and skim milk + 20% added sugar, but not the unsweetened version of each solution. No pre- or postoperative relationship between ghrelin and liking ratings were observed. CONCLUSION: Gut hormone responses following bariatric surgery may contribute to taste processing of sugar+fat mixtures and together influence weight loss.

The Neuro-Endo-Microbio-Ome Study: A Pilot Study of Neurobiological Alterations Pre- Versus Post-Bariatric Surgery.

BACKGROUND: Plausible phenotype mechanisms following bariatric surgery include changes in neural and gastrointestinal physiology. This pilot study aims to investigate individual and combined neurologic, gut microbiome, and plasma hormone changes pre- versus post-vertical sleeve gastrectomy (VSG), Roux-en-Y gastric bypass (RYGB), and medical weight loss (MWL). We hypothesized post-weight loss phenotype would be associated with changes in central reward system brain connectivity, differences in postprandial gut hormone responses, and increased gut microbiome diversity. METHODS: Subjects included participants undergoing VSG, n = 7; RYGB, n = 9; and MWL, n = 6. Ghrelin, glucagon-like peptide-1, peptide-YY, gut microbiome, and resting state functional magnetic resonance imaging (rsfMRI; using fractional amplitude of low-frequency fluctuations [fALFF]) were measured pre- and post-intervention in fasting and fed states. We explored phenotype characterization using clustering on gut hormone, microbiome, and rsfMRI datasets and a combined analysis. RESULTS: We observed more widespread fALFF differences post-bariatric surgery versus post-MWL. Decreased post-prandial fALFF was seen in food reward regions post-RYGB. The highest number of microbial taxa that increased post-intervention occurred in the RYGB group, followed by VSG and MWL. The combined hormone, microbiome, and MRI dataset most accurately clustered samples into pre- versus post-VSG phenotypes followed by RYGB subjects. CONCLUSION: The data suggest surgical weight loss (VSG and RYGB) has a bigger impact on brain and gut function versus MWL and leads to lesser post-prandial activation of food-related neural circuits. VSG subjects had the greatest phenotype differences in interactions of microbiome, rsfMRI, and gut hormone features, followed by RYGB and MWL. These results will inform future prospective research studying gut-brain changes post-bariatric surgery.

The APB study: apixaban pharmacokinetics in bariatric patients before to 1 year after vertical sleeve gastrectomy or Roux-en-Y gastric bypass.

BACKGROUND: The optimal regimen for prevention and treatment of venous thromboembolism in bariatric surgical patients remains controversial. Direct oral anticoagulants are potentially advantageous over other agents, but inadequate evidence exists regarding their effects in bariatric surgical patients. OBJECTIVES: To investigate single-dose pharmacokinetic (PK) and pharmacodynamic (PD) parameters of apixaban when administered to patients undergoing vertical sleeve gastrectomy (VSG) or Roux-en-Y gastric bypass (RYGB) and to determine whether the PK and PD parameters are affected by type of bariatric surgery and weight loss in the immediate and postoperative period up to 12 months. SETTING: University Hospital and A Bariatric Center of Excellence, Baltimore, Maryland. METHODS: Adults with a body mass index ≥35 kg/m2 approved for bariatric surgery were enrolled in a single-center, open-label, nonrandomized, single-dose clinical study (NCT No. 02406885; www. CLINICALTRIALS: gov). Apixaban PK and PD parameters were measured after a single 5 mg dose of the drug was given preoperatively and at 1, 6, and 12 months postoperatively in patients undergoing VSG and RYGB. Change in PK parameters was assessed as maximum concentration, time to maximum concentration, elimination half-life, and area under the concentration-time curve from 0-72 hours and change in PD parameters were assessed by chromogenic factor X activity. RESULTS: Of 33 patients enrolled, 28 (14 VSG, 14 RYGB) completed all visits and were analyzed. Most patients (89%) were female, with a mean age of 43.8 years and a body mass index of 48.7 kg/m2. Area under the concentration-time curve from 0-72 hours increased from baseline to 1 month (1009.1 to 1232.9 ng/mL/hr, P = .002), returned to baseline at 6 months (1000.9 ng/mL/hr, P = .88), and decreased significantly at 12 months (841.8 ng/mL/hr, P = .001). Maximum concentration did not change significantly. Predose factor X activity dropped significantly from 113% preoperatively to 89.8 % at 12 months postoperatively (P < .0001). Three-hour postdose factor X activity was significantly lower at 1, 6, and 12 months postoperatively versus preoperatively. However, the magnitude of the decrease from predose to 3-hour postdose was not significantly altered by surgery. CONCLUSION: The effect of either VSG or RYGB on apixaban PK and PD parameters is minimal. Factor X activity after 5 mg apixaban was lower in postoperative versus preoperative bariatric patients, but this effect appears to be primarily the result of a decrease in factor X activity from bariatric surgery itself and not a postoperative change in apixaban PK and PD parameters. Future studies should investigate the safety, efficacy, and clinical outcomes of apixaban and other direct oral anticoagulants perioperatively and beyond 12 months following bariatric surgery.

One Year Follow-Up of Taste-Related Reward Associations with Weight Loss Suggests a Critical Time to Mitigate Weight Regain Following Bariatric Surgery.

BACKGROUND: Weight regain is a concerning issue in bariatric patients. We previously demonstrated that taste-related reward processing was associated with six-month weight loss outcomes following Roux-en-Y gastric bypass (RYGB) but not vertical sleeve gastrectomy (VSG). Here, we assessed whether these taste factors persisted in predicting weight loss, and weight regain, at one year post-surgery. METHODS: Adult women enrolled in a longitudinal study of taste preferences following bariatric surgery completed behavioral and neuroimaging assessments at one year post-surgery. RESULTS: RYGB produced better weight loss relative to VSG, with weight regain and greater weight loss variability observed from six months to one year post-VSG. Changes in liking for high fat at 2 weeks post-surgery from baseline remained a predictor of weight loss in RYGB, but other predictors did not persist. Average liking ratings rebounded to baseline and higher self-reported food cravings and dietary disinhibition correlated with poorer weight loss at one year post-surgery. CONCLUSION: Initial anatomical and metabolic changes resulting from RYGB that reset neural processing of reward stimuli in the mesolimbic pathway appear to be temporary and may be contingent upon post-operative eating behaviors returning to preoperative obesogenic tendencies. Six months post-surgery may be a critical window for implementing interventions to mitigate weight gain.

Taste-related reward is associated with weight loss following bariatric surgery.

BACKGROUNDBariatric surgeries are the most effective treatments for successful and sustained weight loss, but individuals vary in treatment response. Understanding the neurobiological and behavioral mechanisms accounting for this variation could lead to the development of personalized therapeutic approaches and improve treatment outcomes. The primary objectives of this study were to investigate changes in taste preferences and taste-induced brain responses after Roux-en-Y gastric bypass (RYGB) and vertical sleeve gastrectomy (VSG) and to identify potential taste-related predictors of weight loss.METHODSFemales, ages 18 to 55, with a body mass index greater than or equal to 35 kg/m2, and approved for bariatric surgery at the Johns Hopkins Center for Bariatric Surgery were recruited for participation. Demographics, anthropometrics, liking ratings, and neural responses to varying concentrations of sucrose plus fat mixtures were assessed before and after surgery via visual analog scales and functional MRI.RESULTSBariatric surgery produced decreases in liking for sucrose-sweetened mixtures. Greater preference for sucrose-sweetened mixtures before surgery was associated with greater weight loss in RYGB, but not VSG. In the RYGB group only, individuals who showed lower taste-induced activation in the ventral tegmental area (VTA) before surgery and greater changes in taste-induced VTA activation 2 weeks following surgery experienced increased weight loss.CONCLUSIONThe anatomical and/or metabolic changes associated with RYGB may more effectively "reset" the neural processing of reward stimuli, thereby rescuing the blunted activation in the mesolimbic pathway found in patients with obesity. Further, these findings suggest that RYGB may be particularly effective in patients with a preference for sweet foods.FUNDINGNIH K23DK100559 and Dalio Philanthropies.