Edited by Judit OvádiKeywords: AMP-activated protein kinase b-Subunit Carbohydrate-binding module Glycogen Oligosaccharide a b s t r a c t AMP-activated protein kinase (AMPK) is a heterotrimer of catalytic (a) and regulatory (b and c) subunits with at least two isoforms for each subunit. AMPK b1 is widely expressed whilst AMPK b2 is highly expressed in muscle and both b isoforms contain a mid-molecule carbohydrate-binding module (b-CBM). Here we show that b2-CBM has evolved to contain a Thr insertion and increased affinity for glycogen mimetics with a preference for oligosaccharides containing a single a-1,6 branched residue. Deletion of Thr-101 reduces affinity for single a-1,6 branched oligosaccharides by 3-fold, while insertion of this residue into the equivalent position in the b1-CBM sequence increases affinity by 3-fold, confirming the functional importance of this residue.

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Objective: To evaluate the mechanisms associated with reflux events after sleeve gastrectomy (SG). Summary Background Data: Gastro-esophageal reflux (GERD) post-SG is a critical issue due to symptom severity, impact on quality of life, requirement for reoperation, and potential for Barrett esophagus. The pathophysiology is incompletely delineated. Methods: Post-SG patients, stratified into asymptomatic and symptomatic, underwent protocolized nuclear scintigraphy (n = 83), 24-hour esophageal pH monitoring, and stationary manometry (n = 143) to characterize reflux patterns. Ten patients underwent fasting and postprandial concurrent manometry and pH for detailed analysis of reflux events. Results: Baseline demographics between cohorts were similar: Age 47.2 ± 11.6 versus 44.1 ± 11.3 years (P = 0.121); females 73.2% versus 90.8% (P = 0.005); excess weight loss 53.8 ± 28.1% versus 57.4 ± 25.5% (P = 0.422), follow-up duration 12.3 versus 7.4 months (P = 0.503). Nuclear scintigraphy delineated bolus-induced deglutitive reflux events (29.6% vs 62.5%, P = 0.005) and postprandial reflux events [4 (IQR2) versus 4 (IQR 3) events, P = 0.356]. Total acid exposure was significantly elevated in the symptomatic population (7.7% vs 3.6%, P < 0.001), especially fasting acid exposure (6.0% vs 1.3%, P < 0.001). pH/manometry analysis demonstrated acute elevations of the gastro-esophageal pressure gradient ( > 10 mm Hg) underpinned most reflux events. Swallow-induced intragastric hyper-pressur-ization was associated with individual reflux events in most patients (90% in fasting state and 40% postprandial). Conclusions: We found reflux to be strongly associated with SG and identified 3 unique categories. Bolus-induced deglutitive and postprandial reflux occurred in most patients. Elevated fasting esophageal acid exposure mediated symptoms. Frequent, significant elevation in the gastro-esophageal pressure gradient was the mechanism of reflux and seemed to relate to the noncompliant proximal stomach.

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Background Intermediate to long-term weight regain is a major challenge following sleeve gastrectomy (SG). Physiological changes that mediate the extent of weight loss remain unclear. We aimed to determine if there were specific esophago-gastric transit and emptying alterations associated with weight regain. Material and Methods Participants greater than 12 months post-SG were categorized into optimal (n = 29) and poor weight loss (PWL) (n = 72). All patients underwent a liquid contrast barium swallow demonstrating normal post-surgical anatomy and a protocolized nuclear scintigraphy designed specifically to characterize gastric emptying following SG. Results The %total weight loss in the optimal group was 26.2 ± 10.5 vs. 14.3 ± 8.8% in the PWL group (p = 0.001). Scintigraphy showed PWL had relatively increased gastric emptying half-time (GE 1/2t) 35 (IQR 23) min vs 19 (IQR 5.5) min (p = 0.001). The multivariate regressions delineated GE 1/2t as the best diagnostic measure for PWL (OR 1.16; CI 1.04–1.29, p-value 0.021). The probability of PWL increased by 16% for every 1-min increase above 21 min of GE 1/2t. A threshold of 21 min was found to have 88% sensitivity and 69% specificity predicting poor weight loss. Conclusion Gastric emptying half-times greater than 21 min appear to reliably correlate with poor weight loss following SG. Additionally, further elevations above 21 min in emptying half-time increase the risk of poor weight loss. We have shown nuclear scintigraphy represents a simple and accurate diagnostic tool in patients who experience poor weight loss after SG, provided substantially altered reporting references in interpreting nuclear scintigraphy are applied. Graphical abstract