Bariatric surgery alters mitochondrial function in gut mucosa.

BACKGROUND: The obesity pandemic has worsened global disease burden, including type 2 diabetes, cardiovascular disease, and cancer. Metabolic/bariatric surgery (MBS) is the most effective and durable obesity treatment, but the mechanisms underlying its long-term weight loss efficacy remain unclear. MBS drives substrate oxidation that has been linked to improvements in metabolic function and improved glycemic control that are potentially mediated by mitochondria-a primary site of energy production. As such, augmentation of intestinal mitochondrial function may drive processes underlying the systemic metabolic benefits of MBS. Herein, we applied a highly sensitive technique to evaluate intestinal mitochondrial function ex vivo in a mouse model of MBS. METHODS: Mice were randomized to surgery, sham, or non-operative control. A simplified model of MBS, ileal interposition, was performed by interposition of a 2-cm segment of terminal ileum into the proximal bowel 5 mm from the ligament of Treitz. After a four-week recovery period, intestinal mucosa of duodenum, jejunum, ileum, and interposed ileum were assayed for determination of mitochondrial respiratory function. Citrate synthase activity was measured as a marker of mitochondrial content. RESULTS: Ileal interposition was well tolerated and associated with modest body weight loss and transient hypophagia relative to controls. Mitochondrial capacity declined in the native duodenum and jejunum of animals following ileal interposition relative to controls, although respiration remained unchanged in these segments. Similarly, ileal interposition lowered citrate synthase activity in the duodenum and jejunum following relative to controls but ileal function remained constant across all groups. CONCLUSION: Ileal interposition decreases mitochondrial volume in the proximal intestinal mucosa of mice. This change in concentration with preserved respiration suggests a global mucosal response to segment specific nutrition signals in the distal bowel. Future studies are required to understand the causes underlying these mitochondrial changes.

Bile diversion, a bariatric surgery, and bile acid signaling reduce central cocaine reward.

The gut-to-brain axis exhibits significant control over motivated behavior. However, mechanisms supporting this communication are poorly understood. We reveal that a gut-based bariatric surgery chronically elevates systemic bile acids and attenuates cocaine-induced elevations in accumbal dopamine. Notably, this surgery reduces reward-related behavior and psychomotor sensitization to cocaine. Utilizing a knockout mouse model, we have determined that a main mediator of these post-operative effects is the Takeda G protein-coupled bile acid receptor (TGR5). Viral restoration of TGR5 in the nucleus accumbens of TGR5 knockout animals is sufficient to restore cocaine reward, centrally localizing this TGR5-mediated modulation. These findings define TGR5 and bile acid signaling as pharmacological targets for the treatment of cocaine abuse and reveal a novel mechanism of gut-to-brain communication.

Intestinal Lymph Collection via Cannulation of the Mesenteric Lymphatic Duct in Mice.

BACKGROUND: We have optimized a technique for cannulation of mesenteric lymph duct (MLD) in mice. Mice have low rates of intestinal lymph production; the MLDs are smaller and associated with fragile vasculature. Previous protocols for lymph collection based on the open lymph fistula model were associated with low success rates in mice. Bariatric surgery procedures worsen success rates due to postoperative adhesions and GI rearrangement. We have used this procedure to collect mesenteric lymph from mice undergoing bile diversion from gall bladder to ileum (GB-IL). HYPOTHESIS: We hypothesize that peptide YY (PYY) levels in mesenteric lymph will increase following nutrient delivery in mice undergoing bile diversion from gall bladder to ileum (GB-IL). METHODS AND RESULTS: We observe that cannulation of the MLD using a needled-catheter maintains lymph vessel integrity, prevents excessive lymph leakage, and is less traumatic, leading to high success rates (>95%). PYY levels in mesenteric lymph after GB-IL were significantly higher post nutrient infusion. The procedure takes approximately 20 min; small rodent surgical experience and practice are required for success. CONCLUSIONS: Intestinal lymph can be collected from mice, including those undergoing bariatric surgical procedures with high success rates by cannulation of the mesenteric lymph duct.

Association of Bariatric Surgery With Major Adverse Liver and Cardiovascular Outcomes in Patients With Biopsy-Proven Nonalcoholic Steatohepatitis.

IMPORTANCE: No therapy has been shown to reduce the risk of serious adverse outcomes in patients with nonalcoholic steatohepatitis (NASH). OBJECTIVE: To investigate the long-term relationship between bariatric surgery and incident major adverse liver outcomes and major adverse cardiovascular events (MACE) in patients with obesity and biopsy-proven fibrotic NASH without cirrhosis. DESIGN, SETTING, AND PARTICIPANTS: In the SPLENDOR (Surgical Procedures and Long-term Effectiveness in NASH Disease and Obesity Risk) study, of 25 828 liver biopsies performed at a US health system between 2004 and 2016, 1158 adult patients with obesity were identified who fulfilled enrollment criteria, including confirmed histological diagnosis of NASH and presence of liver fibrosis (histological stages 1-3). Baseline clinical characteristics, histological disease activity, and fibrosis stage of patients who underwent simultaneous liver biopsy at the time of bariatric surgery were balanced with a nonsurgical control group using overlap weighting methods. Follow-up ended in March 2021. EXPOSURES: Bariatric surgery (Roux-en-Y gastric bypass, sleeve gastrectomy) vs nonsurgical care. MAIN OUTCOMES AND MEASURES: The primary outcomes were the incidence of major adverse liver outcomes (progression to clinical or histological cirrhosis, development of hepatocellular carcinoma, liver transplantation, or liver-related mortality) and MACE (a composite of coronary artery events, cerebrovascular events, heart failure, or cardiovascular death), estimated using the Firth penalized method in a multivariable-adjusted Cox regression analysis framework. RESULTS: A total of 1158 patients (740 [63.9%] women; median age, 49.8 years [IQR, 40.9-57.9 years], median body mass index, 44.1 [IQR, 39.4-51.4]), including 650 patients who underwent bariatric surgery and 508 patients in the nonsurgical control group, with a median follow-up of 7 years (IQR, 4-10 years) were analyzed. Distribution of baseline covariates, including histological severity of liver injury, was well-balanced after overlap weighting. At the end of the study period in the unweighted data set, 5 patients in the bariatric surgery group and 40 patients in the nonsurgical control group experienced major adverse liver outcomes, and 39 patients in the bariatric surgery group and 60 patients in the nonsurgical group experienced MACE. Among the patients analyzed with overlap weighting methods, the cumulative incidence of major adverse liver outcomes at 10 years was 2.3% (95% CI, 0%-4.6%) in the bariatric surgery group and 9.6% (95% CI, 6.1%-12.9%) in the nonsurgical group (adjusted absolute risk difference, 12.4% [95% CI, 5.7%-19.7%]; adjusted hazard ratio, 0.12 [95% CI, 0.02-0.63]; P = .01). The cumulative incidence of MACE at 10 years was 8.5% (95% CI, 5.5%-11.4%) in the bariatric surgery group and 15.7% (95% CI, 11.3%-19.8%) in the nonsurgical group (adjusted absolute risk difference, 13.9% [95% CI, 5.9%-21.9%]; adjusted hazard ratio, 0.30 [95% CI, 0.12-0.72]; P = .007). Within the first year after bariatric surgery, 4 patients (0.6%) died from surgical complications, including gastrointestinal leak (n = 2) and respiratory failure (n = 2). CONCLUSIONS AND RELEVANCE: Among patients with NASH and obesity, bariatric surgery, compared with nonsurgical management, was associated with a significantly lower risk of incident major adverse liver outcomes and MACE.

Roux-en-Y gastric bypass surgery improves hepatic glucose metabolism and reduces plasma kisspeptin levels in morbidly obese patients with type 2 diabetes.

Roux-en-Y gastric bypass surgery (RYGB) is known to improve whole-body glucose metabolism in patients with type 2 diabetes (T2D), although the mechanisms are not entirely clear and are likely multifactorial. The aim of this study was to assess fasting hepatic glucose metabolism and other markers of metabolic activity before and after RYGB in patients with and without T2D. Methods: Metabolic characteristics of patients who are obese with T2D were compared with those without the disease (non-T2D) before and 1 and 6 mo after RYGB. Fasting plasma insulin and the insulin:glucagon ratio were markedly reduced as early as 1 mo after RYGB in both patients with T2D and without T2D. Despite this reduction, endogenous glucose production and fasting plasma glucose levels were lower in both groups after RYGB, with the reductions being much larger in T2D. Plasma kisspeptin, an inhibitor of insulin secretion, was reduced only in T2D after surgery. Improved hepatic glucose metabolism and lower plasma kisspeptin in T2D after RYGB may link improved hepatic function with enhanced insulin responsiveness after surgery.NEW & NOTEWORTHY Our manuscript is the first, to the best of our knowledge, to present data showing that Roux-en-Y gastric bypass surgery (RYGB) lowers fasting kisspeptin levels in patients who are obese with type 2 diabetes. This lowering of kisspeptin is important because it could link improvements in liver glucose metabolism after RYGB with increased insulin responsiveness also seen after surgery.

Role of Bile Acids and GLP-1 in Mediating the Metabolic Improvements of Bariatric Surgery.

BACKGROUND & AIMS: Bile diversion to the ileum (GB-IL) has strikingly similar metabolic and satiating effects to Roux-en-Y gastric bypass (RYGB) in rodent obesity models. The metabolic benefits of these procedures are thought to be mediated by increased bile acids, although parallel changes in body weight and other confounding variables limit this interpretation. METHODS: Global G protein-coupled bile acid receptor-1 null (Tgr5-/-) and intestinal-specific farnesoid X receptor null (FxrΔ/E) mice on high-fat diet as well as wild-type C57BL/6 and glucagon-like polypeptide 1 receptor deficient (Glp-1r-/-) mice on chow diet were characterized following GB-IL. RESULTS: GB-IL induced weight loss and improved oral glucose tolerance in Tgr5-/-, but not FxrΔ/E mice fed a high-fat diet, suggesting a role for intestinal Fxr. GB-IL in wild-type, chow-fed mice prompted weight-independent improvements in glycemia and glucose tolerance secondary to augmented insulin responsiveness. Improvements were concomitant with increased levels of lymphatic GLP-1 in the fasted state and increased levels of intestinal Akkermansia muciniphila. Improvements in fasting glycemia after GB-IL were mitigated with exendin-9, a GLP-1 receptor antagonist, or cholestyramine, a bile acid sequestrant. The glucoregulatory effects of GB-IL were lost in whole-body Glp-1r-/- mice. CONCLUSIONS: Bile diversion to the ileum improves glucose homeostasis via an intestinal Fxr-Glp-1 axis. Altered intestinal bile acid availability, independent of weight loss, and intestinal Akkermansia muciniphila appear to mediate the metabolic changes observed after bariatric surgery and might be manipulated for treatment of obesity and diabetes.

Proline Precursors and Collagen Synthesis: Biochemical Challenges of Nutrient Supplementation and Wound Healing.

Wound healing is a complex process marked by highly coordinated immune fluxes into an area of tissue injury; these are required for re-establishment of normal tissue integrity. Along with this cascade of cellular players, wound healing also requires coordinated flux through a number of biochemical pathways, leading to synthesis of collagen and recycling or removal of damaged tissues. The availability of nutrients, especially amino acids, is critical for wound healing, and enteral supplementation has been intensely studied as a potential mechanism to augment wound healing-either by increasing tensile strength, decreasing healing time, or both. From a practical standpoint, although enteral nutrient supplementation may seem like a reasonable strategy to augment healing, a number of biochemical and physiologic barriers exist that limit this strategy. In this critical review, the physiology of enteral amino acid metabolism and supplementation and challenges therein are discussed in the context of splanchnic physiology and biochemistry. Additionally, a review of studies examining various methods of amino acid supplementation and the associated effects on wound outcomes are discussed.

Metabolic responses to exogenous ghrelin in obesity and early after Roux-en-Y gastric bypass in humans.

AIMS: Ghrelin is a gastric-derived hormone that stimulates growth hormone (GH) secretion and has a multi-faceted role in the regulation of energy homeostasis, including glucose metabolism. Circulating ghrelin concentrations are modulated in response to nutritional status, but responses to ghrelin in altered metabolic states are poorly understood. We investigated the metabolic effects of ghrelin in obesity and early after Roux-en-Y gastric bypass (RYGB). MATERIALS AND METHODS: We assessed central and peripheral metabolic responses to acyl ghrelin infusion (1 pmol kg-1 min-1 ) in healthy, lean subjects (n = 9) and non-diabetic, obese subjects (n = 9) before and 2 weeks after RYGB. Central responses were assessed by GH and pancreatic polypeptide (surrogate for vagal activity) secretion. Peripheral responses were assessed by hepatic and skeletal muscle insulin sensitivity during a hyperinsulinaemic-euglycaemic clamp. RESULTS: Ghrelin-stimulated GH secretion was attenuated in obese subjects, but was restored by RYGB to a response similar to that of lean subjects. The heightened pancreatic polypeptide response to ghrelin infusion in the obese was attenuated after RYGB. Hepatic glucose production and hepatic insulin sensitivity were not altered by ghrelin infusion in RYGB subjects. Skeletal muscle insulin sensitivity was impaired to a similar degree in lean, obese and post-RYGB individuals in response to ghrelin infusion. CONCLUSIONS: These data suggest that obesity is characterized by abnormal central, but not peripheral, responsiveness to ghrelin that can be restored early after RYGB before significant weight loss. Further work is necessary to fully elucidate the role of ghrelin in the metabolic changes that occur in obesity and following RYGB.

Arginine-Dual roles as an onconutrient and immunonutrient.

Arginine is an important player in numerous biologic processes and studies have demonstrated its importance for cellular growth that becomes limiting in states of rapid turnover (e.g., malignancy). Thus, arginine deprivation therapy is being examined as an adjuvant cancer therapy, however, arginine is also necessary for immune destruction of malignant cells. Herein we review the data supporting arginine deprivation or supplementation in cancer treatment and the currently registered trials aimed at understanding these divergent strategies. J. Surg. Oncol. 2017;115:273-280. © 2016 Wiley Periodicals, Inc.

Jejunal administration of glucose enhances acyl ghrelin suppression in obese humans.

Ghrelin is a gastric hormone that stimulates hunger and worsens glucose metabolism. Circulating ghrelin is decreased after Roux-en-Y gastric bypass (RYGB) surgery; however, the mechanism(s) underlying this change is unknown. We tested the hypothesis that jejunal nutrient exposure plays a significant role in ghrelin suppression after RYGB. Feeding tubes were placed in the stomach or jejunum in 13 obese subjects to simulate pre-RYGB or post-RYGB glucose exposure to the gastrointestinal (GI) tract, respectively, without the confounding effects of caloric restriction, weight loss, and surgical stress. On separate study days, the plasma glucose curves obtained with either gastric or jejunal administration of glucose were replicated with intravenous (iv) infusions of glucose. These "isoglycemic clamps" enabled us to determine the contribution of the GI tract and postabsorptive plasma glucose to acyl ghrelin suppression. Plasma acyl ghrelin levels were suppressed to a greater degree with jejunal glucose administration compared with gastric glucose administration (P < 0.05). Jejunal administration of glucose also resulted in a greater suppression of acyl ghrelin than the corresponding isoglycemic glucose infusion (P ≤ 0.01). However, gastric and isoglycemic iv glucose infusions resulted in similar degrees of acyl ghrelin suppression (P > 0.05). Direct exposure of the proximal jejunum to glucose increases acyl ghrelin suppression independent of circulating glucose levels. The enhanced suppression of acyl ghrelin after RYGB may be due to a nutrient-initiated signal in the jejunum that regulates ghrelin secretion.

Insurance payor status and risk of major adverse cardiovascular and cerebrovascular events after metabolic and bariatric surgery.

BACKGROUND: Patients with Medicare/Medicaid insurance receive metabolic and bariatric surgery (MBS) at lower rates than privately insured (PI) patients. Although studies on some surgical procedures report that Medicare/Medicaid insurance confers increased postoperative complication rates and a longer length of stay, less is known about these outcomes after MBS. Among often-feared postoperative complications are major adverse cardiovascular and cerebrovascular events (MACEs). Although these events are rare after MBS, they have a significant impact on morbidity and mortality. OBJECTIVES: This study aimed to examine the effect of insurance payor status on MACEs after MBS. SETTING: The Healthcare Cost and Utilization Project National Inpatient Sample (HCUP-NIS). METHODS: HCUP-NIS was queried for cases including sleeve gastrectomy or Roux-en-Y gastric bypass between 2012 and 2019. Bivariate associations between patient-level factors and MACEs were assessed via Rao-Scott χ2 tests. Adjusted and unadjusted risks of insurance payor status for MACEs were evaluated using logistic regression. RESULTS: Incidence of MACEs was higher in both Medicare (.75% versus .11%; P < .001) and Medicaid (.15% versus .11%; P < .001) groups than in the PI group. After adjustment for high-risk demographics, high-risk co-morbidities, socioeconomic variables, and hospital factors, insurance status of Medicare (odds ratio [OR]: 1.60, 95% confidence interval [CI]: 1.23, 2.07; P = .0026) or Medicaid (OR: 1.55, 95% CI: 1.12, 2.16; P = .0026) remained an independent risk factor for MACEs. CONCLUSIONS: Our findings underscore the significance of Medicaid/Medicare payor status as an independent predictor of postoperative MACEs in MBS. The results of this study can have a significant impact on deepening our understanding of socioeconomic and health system-related issues that can be targeted to improve outcomes in both MBS and other surgical specialties.

Early marginal ulceration prevalence following primary RYGB: a rare events model of the MBSAQIP 2015-2021.

PURPOSE: Marginal ulceration (MU) following Roux-en-Y gastric bypass (RYGB) is an established complication, with early MU (within 30-days of operation) being less understood compared to its late counterpart. This study aims to identify risk factors for early MU in patients undergoing primary RYGB. METHODS: Utilizing data from the Metabolic and Bariatric Surgery Accreditation Quality Improvement Project (MBSAQIP 2015-2021), 1,346,468 records were evaluated. After exclusions for revisions, conversions, pediatric cases, nonbinary gender, missing body mass index (BMI) data, and missing operative time; 291,625 cases of primary RYGB were included for full analysis and rare events modeling of early MU. RESULTS: The prevalence of early MU was .29% (n = 850). Higher rates of early MU were associated with BMI, race, history of diabetes mellitus (DM), prior thrombotic complications (deep vein thrombosis (DVT) and pulmonary embolism (PE)), prior percutaneous cardiac intervention (PTC), immunosuppressive therapy, and anticoagulation status. Additionally, procedural aspects like the nonspecialization of the surgeon and longer operative times also correlated with higher early MU rates. Rare-events regression modeling noted significant associations of early MU with younger age, diabetes requiring insulin, history of PTC, DVT, immunosuppressive therapy, and anticoagulation status. CONCLUSION: Early MU remains a relatively rare complication. The lower than previously reported occurrence suggests possible improvements in both patient preparation and surgical technique. The identification of relevant risk factors enables better perioperative and intraoperative management of patients at risk of developing early MU.

Impact of progressive chronic kidney disease stage on postoperative outcomes in metabolic surgery-a propensity-matched analysis using the Metabolic and Bariatric Surgery Accreditation and Quality Improvement database.

BACKGROUND: Metabolic surgery (MS) is effective in improving renal parameters for individuals with obesity and chronic kidney disease (CKD). Despite recognized benefits, concerns linger about the perioperative safety of patients with CKD undergoing MS. This study aimed to identify the CKD stage associated with the most significant increase in postoperative complications. METHODS: The Metabolic and Bariatric Surgery Accreditation and Quality Improvement Program database (2017-2021) was used to identify patients undergoing laparoscopic gastric sleeve (SG) or Roux-en-Y gastric bypass (RYGB). Propensity matching was used to quantify the risk for adverse outcomes associated with progressive CKD stage. RESULTS: In total, 688,583 patients (483,898 without CKD and 204,685 with CKD stages I-V) were examined. Endpoints included length of stay (LOS) >5 days, infection, serious complications, major adverse cardiovascular events (MACE), and death. Both SG and RYGB exhibited a linear increase in risk of infection and death. For SG, patients who were stage IIIa/IIIb demonstrated the greatest risk for LOS >5 days (odds ratio [OR] 1.23; 95% confidence interval [CI] (1.05-1.45); P = .011), serious complications (OR 2.83; 95% CI 1.87-4.30; P < .001), and MACE (OR 2.82; 95% CI 1.81-4.37; P < .001). For RYGB, patients who were stage IIIa/IIIb the exhibited greatest risk of MACE (OR 1.67; 95% CI 1.06-2.62; P = .027). CONCLUSIONS: Although it is generally accepted that worsening CKD correlates with greater surgical risk, this analysis identified CKD stage III as a major inflection point for risk of LOS >5 days, serious complications, and MACE. These findings are useful for counseling and procedure selection and suggest a need for heightened attention to CKD stage III patients undergoing MS.

Limitations of the 2015-2021 Metabolic and Bariatric Surgery Accreditation and Quality Improvement Program database for emergency bariatric operations.

BACKGROUND: The Metabolic and Bariatric Surgery Quality Improvement Project (MBSAQIP) is the largest bariatric surgery-specific clinical data set. OBJECTIVES: In 2020, the definition of emergency cases was altered to include only revisional or conversion cases and not primary cases. The aim of this study was to examine how this change affects the utility of the data set for emergency case tracking. SETTING: MBSAQIP database. METHODS: Emergency cases were extracted from available MBSAQIP data (2015-2021). A comparison of co-morbidity profiles was done, specifically before and after the recent change to how "emergency" is defined in the data set. RESULTS: Eleven thousand and twenty-nine of the 1,048,575 total cases were coded as "emergency cases." From 2015 to 2019, 10,574 emergency cases were performed (∼2115 cases/yr), markedly decreasing in 2020 and 2021 to 455 cases (∼228 cases/yr). Before 2020, the most common procedures were the unlisted procedure of the stomach (45.14%, n = 3101), gastric band removal (25.3%, n = 2676), and reduction of internal hernia (11.8%, n = 1244). Between 2020 and 2021, this distribution changed with Roux-en-Y gastric bypass (RYGB), the most common emergency procedure (29.23%, n = 133). As expected from the change that captured only revisional cases, the average operative length was greater between 2020 and 2021 (127.6 versus 86.5 min). CONCLUSIONS: Capturable emergency cases declined in 2020, a trend related to changing the definition of emergency as part of MBSAQIP standards. This change excludes data on internal hernia reduction and does not likely reflect a real change in the prevalence of emergency bariatric cases. Because capture for emergency cases has diminished, so has any prior utility of using MBSAQIP data for studying emergency cases.

Sex- and operation-dependent effects on 5-year weight loss results of bariatric surgery.

BACKGROUND: Weight loss response after bariatric surgery is highly variable, and several demographic factors are associated with differential responses to surgery. Preclinical studies demonstrate numerous sex-specific responses to bariatric surgery, but whether these responses are also operation dependent is unknown. OBJECTIVE: To examine sex-specific weight loss outcomes up to 5 years after laparoscopic Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy (SG). SETTING: Single center, university, United States. METHODS: Retrospective, observational cohort study including RYGB (n = 5057) and vertical SG (n = 2041) patients from a single, academic health center. Percentage total weight loss (TWL) over time was examined with generalized linear mixed models to determine the main and interaction effects of surgery type on weight loss by sex. RESULTS: TWL demonstrated a strong sex-by-procedure interaction, with women having a significant advantage with RYGB compared with SG (adjusted difference at 5 yr: 8.0% [95% CI: 7.5-8.5]; P < .001). Men also experienced greater TWL over time with RYGB or SG, but the difference was less and clinically insignificant (adjusted difference at 5 yr: 2.9% [2.0-3.8]; P < .001; P interaction between sex and procedure type = .0001). Overall, women had greater TWL than men, and RYGB patients had greater TWL than SG patients (adjusted difference at 5 yr: 3.1% [2.4-3.2] and 6.9% [6.5-7.3], respectively; both P < .0001). Patients with diabetes lost less weight compared with those without (adjusted difference at 5 yr: 3.0% [2.7-3.2]; P < .0001). CONCLUSIONS: Weight loss after bariatric surgery is sex- and procedure-dependent. There is an association suggesting a clinically insignificant difference in weight loss between RYGB and SG among male patients at both the 2- and 5-year postsurgery time points.

BMI ≥ 70: A Multi-Center Institutional Experience of the Safety and Efficacy of Metabolic and Bariatric Surgery Intervention.

PURPOSE: With the escalating prevalence of obesity, healthcare providers are increasingly managing patients with a body mass index (BMI) exceeding 70. The aim of this study was to describe the perioperative experiences of this demographic group at two institutions. METHODS: An analysis encompassing 84 patients presenting with BMI ≥ 70 kg/m2 from two institutions was conducted. Data included patient demographics, 30-day postoperative outcomes, and weight-loss at different intervals (30 days, 6 months, 1 year). Additionally, rates of emergency department (ED) utilization, readmission, and reoperation in the first postoperative year were examined. RESULTS: Most patients were black (66.7%) and female (86.9%) with a mean age of 41.7 years. The majority underwent laparoscopic sleeve gastrectomy (SG, 88.1%). Patients exhibited a marked decrease in BMI (7.84% at 30 days, 20.13% at 6 months, and 26.83% at 1 year). Average length of stay was comparable across procedure (F(3,80) = 0.016, p = .997). While 30-day complications were minimal (0.7%), 14.4% of patients experienced ED visits within 30 days, escalating to 19.6% by six months and 25% at 1 year. Readmission and reoperation rates at 1 year were 6.45% and 4.83%, respectively. CONCLUSION: With global obesity rates rising, clinicians are being challenged to care for patients with BMI ≥ 70 kg/m2. Analysis of two institutions demonstrated low rates of 30-days complications but increased readmission rates and ED utilization in this patient population. Despite increased resource utilization, the study suggests that BMI ≥ 70 kg/m2 alone should not be a deterrent for surgery, emphasizing the need for nuanced care in this expanding demographic.

FGF21 as a mediator of adaptive changes in food intake and macronutrient preference in response to protein restriction.

Free-feeding animals navigate complex nutritional landscapes in which food availability, cost, and nutritional value can vary markedly. Animals have thus developed neural mechanisms that enable the detection of nutrient restriction, and these mechanisms engage adaptive physiological and behavioral responses that limit or reverse this nutrient restriction. This review focuses specifically on dietary protein as an essential and independently defended nutrient. Adequate protein intake is required for life, and ample evidence exists to support an active defense of protein that involves behavioral changes in food intake, food preference, and food motivation, likely mediated by neural changes that increase the reward value of protein foods. Available evidence also suggests that the circulating hormone fibroblast growth factor 21 (FGF21) acts in the brain to coordinate these adaptive changes in food intake, making it a unique endocrine signal that drives changes in macronutrient preference in the context of protein restriction. This article is part of the Special Issue on "Food intake and feeding states".

Clinical Outcomes of Metabolic Surgery on Diuretic Use in Patients With Heart Failure.

The beneficial impacts of metabolic surgery (MS) on patients with heart failure (HF) are incompletely characterized. We aimed to describe the cardiac and metabolic effects of MS in patients with HF and hypothesized that patients with HF would experience both improved metabolic and HF profiles using glycemic control and diuretic dependency as surrogate markers. In this single-center, university-affiliated academic study in the United States, a review of 2,342 hospital records of patients who underwent MS (2017 to 2023) identified 63 patients with a medical history of HF. Preoperative characteristics, 30-day outcomes, and up to 2-year biometric and metabolic outcomes, medication usage, and emergency department utilization were collected. At 24 months, mean body mass index change was -16 kg/m2 (p <0.001) that corresponded to a mean percentage total body weight loss of 29% (p <0.001). Weight loss was accompanied by significant reductions in hemoglobin A1c (p <0.001) and a 65% decrease in diuretic use at 24 months after surgery (p <0.001). Similarly, emergency visits for cardiac conditions (p = 0.06) and intravenous diuresis (p = 0.07) trended favorably at 1 year after surgery compared with 1 year before surgery but were not statistically significant. In conclusion, in patients with HF who were carefully selected, MS appears to provide significant reduction in oral diuretic dependency, and metabolic improvements with trends toward lower rates of emergency department utilization.

Enhanced Patient Portal Engagement Associated with Improved Weight Loss Outcomes in Post-Bariatric Surgery Patients.

Background: Bariatric surgery is an effective intervention for obesity, but it requires comprehensive postoperative self-management to achieve optimal outcomes. While patient portals are generally seen as beneficial in engaging patients in health management, the link between their use and post-bariatric surgery weight loss remains unclear. Objective: This study investigated the association between patient portal engagement and postoperative body mass index (BMI) reduction among bariatric surgery patients. Methods: This retrospective longitudinal study included patients who underwent Roux-en-Y gastric bypass (RYGB) or sleeve gastrectomy (SG) at Vanderbilt University Medical Center (VUMC) between January 2018 and March 2021. Using generalized estimating equations, we estimated the association between active days of postoperative patient portal use and the reduction of BMI percentage (%BMI) at 3, 6, and 12 months post-surgery. Covariates included duration since surgery, the patient's age at the time of surgery, gender, race and ethnicity, type of bariatric surgery, severity of comorbid conditions, and socioeconomic disadvantage. Results: The study included 1,415 patients, mostly female (80.9%), with diverse racial and ethnic backgrounds. 805 (56.9%) patients underwent RYGB and 610 (43.1%) underwent SG. By one-year post-surgery, the mean (SD) %BMI reduction was 31.1% (8.3%), and the mean (SD) number of patient portal active days was 61.0 (41.2). A significantly positive association was observed between patient portal engagement and %BMI reduction, with variations revealed over time. Each 10-day increment of active portal use was associated with a 0.57% ([95% CI: 0.42- 0.72], P < .001) and 0.35% ([95% CI: 0.22- 0.49], P < .001) %BMI reduction at 3 and 6 months postoperatively. The association was not statistically significant at 12 months postoperatively (ß=-0.07, [95% CI: -0.24- 0.09], P = .54). Various portal functions, including messaging, visits, my record, medical tools, billing, resources, and others, were positively associated with %BMI reduction at 3- and 6-months follow-ups. Conclusions: Greater patient portal engagement, which may represent stronger adherence to postoperative instructions, better self-management of health, and enhanced communication with care teams, was associated with improved postoperative weight loss. Future investigations are needed to identify important portal features that contribute to the long-term success of weight loss management.

FGF21 acts in the brain to drive macronutrient-specific changes in behavioral motivation and brain reward signaling.

Dietary protein restriction induces adaptive changes in food preference, increasing protein consumption over carbohydrates or fat. We investigated whether motivation and reward signaling underpin these preferences. In an operant task, protein-restricted male mice increased their responding for liquid protein rewards, but not carbohydrate, fat, or sweet rewards. The protein restriction-induced increase in operant responding for protein was absent in Fgf21-KO mice and mice with neuron-specific deletion of the FGF21 co-receptor beta-Klotho (KlbCam2ka) mice. Fiber photometry recording of VTA dopamine neurons revealed that oral delivery of maltodextrin triggered a larger activation of dopamine neurons as compared to casein in control-fed mice, while casein produced a larger response in protein-restricted mice. This restriction-induced shift in nutrient-specific VTA dopamine signaling was lost in Fgf21-KO mice. These data demonstrate that FGF21 acts in the brain to induce a protein-specific appetite by specifically enhancing the reward value of protein-containing foods and the motivation to consume them.