Weight Regain and Ingestive Behavior in Women after Metabolic Surgery.

This study investigated associations between maladaptive ingestive behaviors and weight regain in women who underwent metabolic surgery 2-10 years ago. Using a web-based survey, we assessed emotional, external, and restrained eating (Dutch Eating Behavior Questionnaire-DEBQ), food cravings (Food-Craving Inventory-FCI), and other behaviors (e.g., Eating Disorder Examination Questionnaire-EDE-Q; Alcohol Use Disorder Identification Test-Concise-AUDIT-C) in 36 women (42.9 ± 9.5 years old) post-surgery. We found that weight regain was specifically associated with increased frequency of cravings for sweets (r = 0.43), higher global scores in the EDE-Q (r = 0.38), and time elapsed since surgery (r = 0.35; all p's < 0.04). Multiple regression analysis revealed that the association between weight regain and sweet cravings interacted with time after surgery (p = 0.04), with the strongest association observed in women assessed closer to the surgery (i.e., 2.0-2.8 years). The combination of time after surgery and its interaction with sweet cravings accounted for 31% of the individual variations in weight regain (p = 0.005). Notably, among participants who reported alcohol consumption (31 of 36), 55% had an AUDIT-C score indicating hazardous drinking. These findings highlight the relevance of attending to patients' reports of frequent sweet cravings and screening for alcohol use to enhance strategies tailored to prevent weight regain and alcohol-related health problems post-surgery.

Fat-free mass accounts for most of the variance in alcohol elimination rate in women.

BACKGROUND: Understanding how blood alcohol concentrations (BAC) achieved after drinking are determined is critical to predicting alcohol exposure to the brain and other organs and alcohol's effects. However, predicting end-organ exposures is challenging, as there is wide variation in BAC achieved after drinking a specified volume of alcohol. This variation is partly due to differences in body composition and alcohol elimination rates (AER), but there are limited data on how obesity affects AER. Here, we assess associations between obesity, fat-free mass (FFM), and AER in women and examine whether bariatric surgeries, which are linked to an increased risk of alcohol misuse, affect these associations. METHODS: We analyzed data from three studies that used similar intravenous alcohol clamping procedures to estimate AER in 143 women (21 to 64 years old) with a wide range of body mass index (BMI; 18.5 to 48.4 kg/m2 ). Body composition was measured in a subgroup using dual-energy X-ray absorptiometry (n = 42) or Bioimpedance (n = 60), and 19 of the women underwent bariatric surgery 2.1 ± 0.3 years before participation. We analyzed data using multiple linear regression analyses. RESULTS: Obesity and older age were associated with a faster AER (BMI: rs  = 0.70 and age: rs  = 0.61, both p < 0.001). Compared to women with normal weight, AER was 52% faster (95% Confidence Interval: 42% to 61%) in women with obesity. However, BMI lost predictive value when adding fat-free mass (FFM) to the regression model. Age, FFM, and its interaction explained 72% of individual variance in AER (F (4, 97) = 64.3, p < 0.001). AER was faster in women with higher FFM, particularly women in the top tertile of age. After controlling for FFM and age, bariatric surgery was not associated with differences in AER (p = 0.74). CONCLUSIONS: Obesity is associated with a faster AER, but this association is mediated by an obesity-related increase in FFM, particularly in older women. Previous findings of a reduced alcohol clearance following bariatric surgery compared with prior to surgery are likely explained by a reduction in FFM post-surgery.

Pathological bile acid concentrations in chronic cholestasis cause adipose mitochondrial defects.

Background & Aims: Although fat loss is observed in patients with cholestasis, how chronically elevated bile acids (BAs) impact white and brown fat depots remains obscure. Methods: To determine the direct effect of pathological levels of BAs on lipid accumulation and mitochondrial function, primary white and brown adipocyte cultures along with fat depots from two separate mouse models of cholestatic liver diseases, namely (i) genetic deletion of farnesoid X receptor (Fxr); small heterodimer (Shp) double knockout (DKO) and (ii) injury by 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC), were used. Results: As expected, cholestatic mice accumulate high systemic BA levels and exhibit fat loss. Here, we demonstrate that chronic exposure to pathological BA levels results in mitochondrial dysfunction and defective thermogenesis. Consistently, both DKO and DDC-fed mice exhibit lower body temperature. Importantly, thermoneutral (30 °C) housing of the cholestatic DKO mice rescues the decrease in brown fat mass, and the expression of genes responsible for lipogenesis and regulation of mitochondrial function. To overcome systemic effects, primary adipocyte cultures were treated with pathological BA concentrations. Mitochondrial permeability and respiration analysis revealed that BA overload is sufficient to reduce mitochondrial function in primary adipocytes, which is not as a result of cytotoxicity. Instead, we found robust reductions in uncoupling protein 1 (Ucp1), PR domain containing 16 (Prdm16), and deiodinase, iodothyronine, type II (Dio2) transcripts in brown adipocytes upon treatment with chenodeoxycholic acid, whereas taurocholic acid led to the suppression of Dio2 transcript. This BA-mediated decrease in transcripts was alleviated by pharmacological activation of UCP1. Conclusions: High concentrations of BAs cause defective thermogenesis by reducing the expression of crucial regulators of mitochondrial function, including UCP1, which may explain the clinical features of hypothermia and fat loss observed in patients with cholestatic liver diseases. Impact and Implications: We uncover a detrimental effect of chronic bile acid overload on adipose mitochondrial function. Pathological concentration of different BAs reduces the expression of distinct genes involved in energy expenditure, which can be mitigated with pharmacological UCP1 activation.

Computed tomography-guided additive manufacturing of Personalized Absorbable Gastrointestinal Stents for intestinal fistulae and perforations.

Small bowel perforations and obstructions are relatively frequent surgical emergencies, are potentially life-threatening, and have multiple etiologies. In general, treatment requires urgent surgical repair or resection and at times can lead to further complications. Stents may be used to help with healing intestinal perforations but use is limited as currently available stents are non-absorbable, are manufactured in a narrow size range, and/or are limited to usage in locations that are accessible for endoscopic removal post-healing. The use of 3D-printed bioresorbable polymeric stents will provide patients with a stent that can prevent leakage, is tailored specifically to their geometry, and will be usable within the small bowel, which is not amenable to endoscopic stent placement. This work focused on the rapid manufacturing of gastrointestinal stents composed of a polycaprolactone-polydioxanone (PCL-PDO) composite. Dynamic Mechanical Analysis (DMA) tests were conducted to separately analyze the effects of composition, the filament formation process, and physiological temperature on the PCL-PDO material properties. The proposed stent design was then modeled using computer-aided design, and Finite Element Analysis (FEA) was used to simulate the effects of physiologically relevant forces on stent integrity. The presence of hydrolysable ester bonds was confirmed using FT-IR spectroscopy. In vitro studies were used to evaluate the biocompatibility of the polymer composite. Further analyses were conducted through stent placement in ex vivo pig intestines. PCL-PDO stents were then 3D-printed and placed in vivo in a pig model.

Alcohol sensitivity in women after undergoing bariatric surgery: a cross-sectional study.

BACKGROUND: Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy (SG), the most common bariatric surgeries performed worldwide, increase the risk to develop an alcohol use disorder. This might be due, in part, to surgery-related changes in alcohol pharmacokinetics. Another risk factor, unexplored within this population, is having a reduced subjective response to alcohol's sedative effects. OBJECTIVES: To assess whether the alcohol sensitivity questionnaire (ASQ), a simple self-report measure, could pinpoint reduced alcohol sensitivity in the bariatric population. SETTING: University medical centers in Missouri and Illinois. METHODS: Women who had RYGB (n = 16), SG (n = 28), or laparoscopic adjustable gastric banding surgery (n = 11) within the last 5 years completed the ASQ for both pre- and postsurgical timeframes, and 45 of them participated in oral alcohol challenge testing postsurgery. Blood alcohol concentration (BAC) and subjective stimulation and sedation were measured before and for 3.5 hours after drinking. RESULTS: In line with faster and higher peak BACs after RYGB and SG than laparoscopic adjustable gastric banding surgery (P < .001), postsurgery ASQ scores were more reduced from presurgery scores after RYGB/SG than after laparoscopic adjustable gastric banding surgery (-2.3 ± .3 versus -1.2 ± .2; P < .05). However, despite the dramatic changes in BAC observed when ingesting alcohol after RYGB/SG surgeries, which resulted in peak BAC that were approximately 50% above the legal driving limit, a third of these women felt almost no alcohol-related sedative effects. CONCLUSIONS: Although RYGB/SG dramatically increased sensitivity to alcohol in all participants, meaningful interindividual differences remained. The ASQ might help identify patients at increased risk to develop an alcohol use disorder after surgery.

Larger omental adipocytes correlate with greater Fetuin-A reduction following sleeve gastrectomy.

BACKGROUND: Shortly after bariatric surgery, insulin sensitivity improves and circulating Fetuin-A (FetA) declines. Elevated FetA may decrease insulin sensitivity by inhibiting insulin receptor autophosphorylation. FetA also mediates inflammation through toll-like receptor 4 and influences monocyte migration and macrophage polarization in the adipocyte. The role of dietary changes on FetA is unclear. It is also unknown whether changes in FetA are associated with adipocyte size, an indicator of insulin sensitivity. METHODS: Sleeve gastrectomy patients (n = 39) were evaluated prior to the preoperative diet, on the day of surgery (DOS) and six-weeks postoperatively. At each visit, diet records, anthropometrics and fasting blood were collected. Adipocyte diameter was measured in omental adipose collected during surgery. RESULTS: Although significant weight loss did not occur during the preoperative diet, HOMA-IR improved (p < 0.0001) and FetA decreased by 12% (p = 0.01). Six-weeks postoperatively, patients lost 9% of body weight (p = 0.02) and FetA decreased an additional 26% (p < 0.0001). HOMA-IR was unchanged during this time. Omental adipocyte size on DOS was not associated with preoperative changes in dietary intake, body composition or HOMA-IR. However, adipocyte size was strongly associated with both pre- (r = 0.41, p = 0.03) and postoperative (r = - 0.44, p = 0.02) change in FetA. CONCLUSION: FetA began to decrease during the preoperative diet. Greater FetA reduction during this time was associated with smaller adipocytes on DOS. Therefore, immediate, post-bariatric improvements in glucose homeostasis may be partly explained by dietary changes. The preoperative diet protocol significantly reduced insulin resistance, a modifiable risk factor for other non-bariatric procedures. Therefore, this dietary protocol may also be used preoperatively for procedures beyond bariatric surgery.

Insulin/IGF-1 enhances intestinal epithelial crypt proliferation through PI3K/Akt, and not ERK signaling in obese humans.

The intestinal epithelium is continuously regenerated through proliferation and differentiation of stem cells located in the intestinal crypts. Obesity affects this process and results in greater stem cell proliferation and altered tissue growth and function. Obesity-induced high levels of insulin and insulin-like growth factor-1 in the stem cell niche are found to impact proliferation in rodents indicating that insulin and insulin-like growth factor-1 receptors may play a role in modulating intestinal epithelial stem cell proliferation. To determine whether insulin or insulin-like growth factor-1 can induce proliferation in human intestinal epithelial stem cells, and if two downstream insulin and insulin-like growth factor-1 receptor signaling pathways, PI3K/Akt and ERK, are involved, we used primary small intestinal epithelial crypts isolated from obese humans and investigated (1) the effect of insulin or insulin-like growth factor-1 on crypt proliferation, and (2) the effect of insulin and insulin-like growth factor-1 signaling inhibitors on insulin or insulin-like growth factor-1-induced proliferation. We found that insulin and insulin-like growth factor-1 enhanced the proliferation of crypt cells, including intestinal epithelial stem cells. Inhibition of the PI3K/Akt pathway attenuated insulin and insulin-like growth factor-1-induced proliferation, but inhibition of the ERK pathway had no effect. These results suggest that the classical metabolic PI3K pathway and not the canonical proliferation ERK pathway is involved in the insulin/insulin-like growth factor-1-induced increase in crypt proliferation in obese humans, which may contribute to abnormal tissue renewal and function. Impact statement This study investigates if insulin or insulin-like growth factor-1 (IGF-1) induces intestinal epithelial proliferation in humans, and if insulin and IGF-1 receptor signaling is involved in this process in obesity. Although obesity-induced high levels of insulin and IGF-1 in the stem cell niche are found to impact the proliferation of intestinal epithelial stem cells in rodents, we are the first to investigate this effect in humans. We found that insulin and IGF-1 enhanced the proliferation of intestinal crypts (including stem cells and other crypt cells) isolated from obese humans, and PI3K/Akt, and not ERK signaling was involved in insulin or IGF-1-induced proliferation. The imbalance in signaling between PI3K/Akt and ERK pathways may point to a pathway-specific impairment in insulin/IGF-1 receptor signaling. We propose that this may contribute to reciprocal relationships between insulin/IGF-1 receptor resistance and intestinal epithelial proliferation that leads to abnormal tissue renewal and function.

Obesity in trauma: outcomes and disposition trends.

BACKGROUND: Obesity's effect on the outcomes of trauma patients remains inconclusive. METHODS: A retrospective review of all falls, motor vehicle collisions (MVCs), and penetrating trauma patients admitted from January 2008 to December 2012 was performed. The outcomes evaluated included mortality, length of stay at hospital, and discharge disposition. Patients were grouped according to the body mass index (BMI) and stratified by injury severity scores. RESULTS: Two thousand one hundred ninety six patients were analyzed; 132 penetrating, 913 falls, and 1,151 MVCs. Penetrating traumas had no significant difference in outcomes. In falls, obese patients had a lower mortality (P = .035). In MVCs, obese patients had longer hospitalizations (P = .02), and mild and moderate MVC injuries were less likely to be discharged home (P = .032 and .003). Obese patients sustained fewer head injuries in falls and MVCs (P = .005 and .043, respectively). CONCLUSIONS: In falls, a higher BMI may benefit patients. However, an increasing BMI is associated with a longer length of stay at hospital, and decreased likelihood of discharge to home.