Effectiveness of anti-obesity medications approved for long-term use in a multidisciplinary weight management program: a multi-center clinical experience.

BACKGROUND AND AIMS: Randomized clinical trials have proven the efficacy and safety of Food and Drug Administration (FDA) approved anti-obesity medications (AOMs) for long-term use. It is unclear whether these outcomes can be replicated in real-world clinical practice where clinical complexities arise. The aim of this study was to evaluate the effectiveness and side effects of these medications in real-world multidisciplinary clinical practice settings. METHODS: We reviewed the electronic medical records (EMR) of patients with obesity who were prescribed an FDA-approved AOM for long-term use in academic and community multidisciplinary weight loss programs between January 2016 and January 2020. INTERVENTION: We assessed percentage total body weight loss (%TBWL), metabolic outcomes, and side effect profile up to 24 months after AOM initiation. RESULTS: The full cohort consisted of 304 patients (76% women, 95.2% White, median age of 50 years old [IQR, 39-58]). The median follow-up time was 9.1 months [IQR, 4.2-14.1] with a median number of 3 visits [IQR, 2-4]. The most prescribed medication was phentermine/topiramate extended-release (ER) (51%), followed by liraglutide (26.3%), bupropion/naltrexone sustained-release (SR) (16.5%), and lorcaserin (6.2%). %TBWL was 5.0%, 6.8%, 9.3%, 10.3%, and 10.5% at 3, 6, 12, 18, and 24 months. 60.2% of the entire cohort achieved at least 5% TBWL. Overall, phentermine/topiramate-ER had the most robust weight loss response during follow-up, with the highest %TBWL at 12 months of 12.0%. Adverse events were reported in 22.4% of patients. Only 9% of patients discontinued the medication due to side effects. CONCLUSIONS: AOMs resulted in significant long-term weight loss, that was comparable to outcomes previously reported in clinical trials.

The effect of gender and obesity in modulating cross-bridge function in cardiac muscle fibers.

The effect of obesity on cross-bridge (CB) function was investigated in mice lacking functional Melanocortin-4 Receptor (MC4R-/-), the loss of which causes dilated cardiomyopathy (DCM) in humans and mice. Skinned cardiac muscle fibers from male and female mice were used, and activated in the presence of Ca2+. To characterize CB kinetics, we changed the length of fibers in sinewaves (15 frequencies: 1‒187 Hz) at a small amplitude (0.2%L0), studied concomitant tension transients, and deduced the kinetic constants of the CB cycle from the ATP and Pi effects. In males, active tension and stiffness during full activation and rigor were ~ 1.5X in WT compared to MC4R-/- mice. This effect was not observed in females. We also observed that ATP binding and subsequent CB detachment steps were not altered by the mutation/gender. The equilibrium constant of the force generation step (K4) and Pi release step (association constant: K5) were not affected by the mutation, but there was a gender difference in WT mice: K4 and K5 were ~ 2.2X in males than in females. Concomitantly, the forward rate constant (r4) and backward rate constant (r-4) of the force generation step were 1.5-2.5X in muscles from female MC4R-/- mice relative to male MC4R-/- mice. However, these effects did not cause a significant difference in CB distributions among six CB states. In both genders, Ca2+ sensitivity decreased slightly (0.12 pCa unit) in mutants. We conclude that the CB functions are differentially affected both by obesity induced in the absence of functional MC4R-/- and gender.

Direct endoscopic placement of percutaneous endoscopic gastrostomies with jejunal extension tubes (PEG-J) using ultra-thin endoscopes - long-term outcomes from a U.S. tertiary referral center.

INTRODUCTION: Several techniques for PEG-J tube placement have been described, commonly requiring fluoroscopic guidance and/or fixation of the jejunostomy tube (J-tube) into the small intestine. We describe a modified technique for placing jejunostomy tubes under direct visualization through a PEG with the use of ultra-thin endoscopes and steel guidewire. METHODS: A retrospective study at a single tertiary academic center evaluating patients who underwent PEG-J placement between 2010 and 2020. All PEG tubes were placed with a pull-through technique. The Olympus GIF-N180 endoscope was advanced through the PEG to the jejunum and a Savary-Gilliard guidewire was used for placement of the J-tube extension. RESULTS: Fifty-eight patients underwent PEG-J placement (median age 61 years; women 52%). Surgically altered gastric anatomy was observed in 11 patients (19%). Median procedure time was 44 min for new PEG-J tube placement (range 26-103) and 20 min for placement of a J-tube extension through an existing PEG tube (range 9-86) or gastrostomy tract. Technical success rate was in 100%. Sixty-two repeat procedures were performed for J-tube exchange in 27 patients (46%, range 1-9 per patient), of which 51 procedures (82%) were done using the same technique. The most common indication for tube replacement was tube dysfunction (63%, n = 39). The median procedure time for tube exchange was 20 min (range 2-62). No major adverse events were encountered. CONCLUSION: PEG-J tubes can be placed effectively, rapidly, and safely using an ultra-thin caliber endoscope and a stiff steel wire through the PEG tube or mature gastrostomy site, precluding the need for fluoroscopy or oral access. J-tubes can be easily replaced utilizing the same technique.

Copper metabolism domain-containing 1 represses genes that promote inflammation and protects mice from colitis and colitis-associated cancer.

BACKGROUND & AIMS: Activation of the transcription factor nuclear factor-κB (NF-κB) has been associated with the development of inflammatory bowel disease (IBD). Copper metabolism MURR1 domain containing 1 (COMMD1), a regulator of various transport pathways, has been shown to limit NF-κB activation. We investigated the roles of COMMD1 in the pathogenesis of colitis in mice and IBD in human beings. METHODS: We created mice with a specific disruption of Commd1 in myeloid cells (Mye-knockout [K/O] mice); we analyzed immune cell populations and functions and expression of genes regulated by NF-κB. Sepsis was induced in Mye-K/O and wild-type mice by cecal ligation and puncture or intraperitoneal injection of lipopolysaccharide (LPS), colitis was induced by administration of dextran sodium sulfate, and colitis-associated cancer was induced by administration of dextran sodium sulfate and azoxymethane. We measured levels of COMMD1 messenger RNA in colon biopsy specimens from 29 patients with IBD and 16 patients without (controls), and validated findings in an independent cohort (17 patients with IBD and 22 controls). We searched for polymorphisms in or near COMMD1 that were associated with IBD using data from the International IBD Genetics Consortium and performed quantitative trait locus analysis. RESULTS: In comparing gene expression patterns between myeloid cells from Mye-K/O and wild-type mice, we found that COMMD1 represses expression of genes induced by LPS. Mye-K/O mice had more intense inflammatory responses to LPS and developed more severe sepsis and colitis, with greater mortality. More Mye-K/O mice with colitis developed colon dysplasia and tumors than wild-type mice. We observed a reduced expression of COMMD1 in colon biopsy specimens and circulating leukocytes from patients with IBD. We associated single-nucleotide variants near COMMD1 with reduced expression of the gene and linked them with increased risk for ulcerative colitis. CONCLUSIONS: Expression of COMMD1 by myeloid cells has anti-inflammatory effects. Reduced expression or function of COMMD1 could be involved in the pathogenesis of IBD.

Atypical presentation of an epiphrenic esophageal diverticulum 20 years post fundoplication: a case report and review.

Esophageal diverticulum is a rare condition characterized by the herniation of the esophageal mucosa outside the esophageal wall. Here, we explore the prevalence of ED and its associated esophageal dysmotility. We also shed light on the potential impact of previous surgical interventions, such as Nissen's fundoplication, on the development of ED. This manuscript presents the case of a 72-year-old woman with a history of Nissen's fundoplication surgery who experienced worsening symptoms of dysphagia, heartburn and postprandial cough. Despite exhibiting a normal motility pattern, upper endoscopy revealed a large epiphrenic esophageal diverticulum. The patient underwent successful surgical resection with myotomy, resulting in the resolution of symptoms with no complications. This case highlights the rarity of symptomatic ED and the need to recognize it while choosing the optimal treatment modality.

Pharmaco-endoscopic therapy for weight regain post-gastric bypass: a case report.

About 1 in every 4 patients who undergo bariatric surgery regains significant amount of weight some time along their journey, posing it as a serious problem that needs to be addressed in a pandemic of obesity. Lifestyle modification, anti-obesity medications, and bariatric endoscopy are multiple therapeutic options that can be used to support any weight loss attempt. A 53-year-old woman with morbid obesity who responded adequately to gastric-bypass regained significant weight 8 years later. We initially approached her post-operative weight regain in a behavioral, pharmacologic non-invasive manner; however, she failed to appropriately respond to several anti-obesity medications. Upper endoscopy revealed a dilated gastric pouch and gastro-jejunal anastomosis (GJA) that was reduced using argon plasma coagulation (APC), but also with a modest response. We then added liraglutide to her APC endo-therapy sessions and subsequentially patient started losing significantly more weight. For selective post-bariatric surgery weight re-gainers, endoscopic and pharmaco-therapy combined may be needed for more effective results.

Candy cane syndrome presenting with refractory heartburn 15 years after Roux-en-Y bypass.

Candy cane syndrome (CCS) is a rare complication of Roux-en-Y gastric bypass (RYGB), in which the afferent jejunal limb is excessively long. Common symptoms include abdominal pain, nausea and vomiting. A 57-year-old female with a history of RYGB 15 years prior to presentation reported 7 months of persistent heartburn refractory to proton pump inhibitors. Upper endoscopy revealed a 9 cm blind, afferent jejunal limb. After the blind limb was resected laparoscopically, her symptoms resolved. Fifteen years is the longest duration reported from time of RYGB to symptom onset of CCS. Furthermore, heartburn is less frequently seen as a presenting complaint of CCS. Clinicians should thus maintain a high index of suspicion for CCS in patients with refractory heartburn and a history of RYGB, regardless of how long ago the RYGB was performed.

Toll-like Receptor 4 Differentially Modulates Cardiac Function in Response to Chronic Exposure to High-Fat Diet and Pressure Overload.

BACKGROUND/AIM: The impact of myocardial stressors such as high-fat diet (HFD) and pressure overload has been extensively studied. Toll-like receptor 4 (TLR4) deficiency has been suggested to have a protective role in response to these stressors, although some conflicting data exist. Furthermore, there is limited information about the role of TLR4 on cardiac remodeling in response to long-term exposure to stressors. This study aims to investigate the effects of TLR4 deficiency on cardiac histology and physiology in response to chronic stressors. METHODS: TLR4-deficient (TLR4-/-) and wild-type (WT) mice were subjected to either HFD or a normal diet (ND) for 28 weeks. Another group underwent abdominal aortic constriction (AAC) or a sham procedure and was monitored for 12 weeks. Inflammatory markers, histology, and echocardiography were used to assess the effects of these interventions. RESULTS: TLR4-/- mice exhibited reduced cardiac hypertrophy and fibrosis after long-term HFD exposure compared to ND without affecting cardiac function. On the other hand, TLR4 deficiency worsened cardiac function in response to AAC, leading to decreased ejection fraction (EF%) and increased end-systolic volume (ESV). CONCLUSIONS: TLR4 deficiency provided protection against HFD-induced myocardial inflammation but impaired hemodynamic cardiac function under pressure overload conditions. These findings highlight the crucial role of TLR4 and its downstream signaling pathway in maintaining cardiac output during physiologic cardiac hypertrophy in response to pressure overload.

Gastric bypass alters diurnal feeding behavior and reprograms the hepatic clock to regulate endogenous glucose flux.

The molecular clock machinery regulates several homeostatic rhythms, including glucose metabolism. We previously demonstrated that Roux-en-Y gastric bypass (RYGB) has a weight-independent effect on glucose homeostasis and transiently reduces food intake. In this study we investigate the effects of RYGB on diurnal eating behavior as well as on the molecular clock and this clock's requirement for the metabolic effects of this bariatric procedure in obese mice. We find that RYGB reversed the high-fat diet-induced disruption in diurnal eating pattern during the early postsurgery phase of food reduction. Dark-cycle pair-feeding experiments improved glucose tolerance to the level of bypass-operated animals during the physiologic fasting phase (Zeitgeber time 2, ZT2) but not the feeding phase (ZT14). Using a clock gene reporter mouse model (mPer2Luc), we reveal that RYGB induced a liver-specific phase shift in peripheral clock oscillation with no changes to the central clock activity within the suprachiasmatic nucleus. In addition, we show that weight loss effects were attenuated in obese ClockΔ19 mutant mice after RYGB that also failed to improve glucose metabolism after surgery, specifically hepatic glucose production. We conclude that RYGB reprograms the peripheral clock within the liver early after surgery to alter diurnal eating behavior and regulate hepatic glucose flux.

Role of the Autonomic Nervous System in Mechanism of Energy and Glucose Regulation Post Bariatric Surgery.

Even though lifestyle changes are the mainstay approach to address obesity, Sleeve gastrectomy (SG) and Roux-en-Y gastric bypass (RYGB) are the most effective and durable treatments facing this pandemic and its associated metabolic conditions. The traditional classifications of bariatric surgeries labeled them as "restrictive," "malabsorptive," or "mixed" types of procedures depending on the anatomical rearrangement of each one of them. This conventional categorization of bariatric surgeries assumed that the "restrictive" procedures induce their weight loss and metabolic effects by reducing gastric content and therefore having a smaller reservoir. Similarly, the "malabsorptive" procedures were thought to induce their main energy homeostatic effects from fecal calorie loss due to intestinal malabsorption. Observational data from human subjects and several studies from rodent models of bariatric surgery showed that neither of those concepts is completely true, at least in explaining the multiple metabolic changes and the alteration in energy balance that those two surgeries induce. Rather, neuro-hormonal mechanisms have been postulated to underly the physiologic effects of those two most performed bariatric procedures. In this review, we go over the role the autonomic nervous system plays- through its parasympathetic and sympathetic branches- in regulating weight balance and glucose homeostasis after SG and RYGB.

Toll-like receptor 4 and myeloid differentiation factor 88 are required for gastric bypass-induced metabolic effects.

BACKGROUND: Toll-like receptor 4 (TLR4) has been suggested as one of the forefront cross-communicators between the intestinal bacteria and the host to regulate inflammatory signals and energy homeostasis. High-fat diet-induced inflammation is mediated by changes in gut microbiota and requires a functional TLR-4, the deficiency of which renders mice resistant to diet-induced obesity and its associated metabolic dysfunction. Furthermore, gut microbiota was suggested to play a key role in the beneficial effects of Roux-en-Y gastric bypass (RYGB), a commonly performed bariatric procedure. OBJECTIVES: To explore whether TLR4, myeloid differentiation factor 8 (MyD88; 1 of its key downstream signaling regulators) and gut microbiota play an integrative role in RYGB-induced metabolic outcomes. SETTING: Animal- based study. METHOD: We performed RYGB in TLR4 and MyD88 knock-out (KO) mice and used fecal microbiota transplant (FMT) from RYGB-operated animals to these genetic mouse models to address our questions. RESULTS: We demonstrate that RYGB reduces TLR4 expression explicitly in the small and large intestine of C57Blc/6J mice. We also show that TLR4 KO mice have an attenuated glucoregulatory response to RYGB. In addition, we reveal that MyD88 KO mice fail to respond to all RYGB-induced metabolic effects. Finally, fecal microbiota transplant from RYGB-operated mice into TLR4 KO and MyD88 KO naïve recipients fails to induce a metabolic phenotype similar to that of the donors, as it does in wild-type recipients. CONCLUSION: TLR4 and MyD88 are required for RYGB-induced metabolic response that is likely mediated by gut microbiome.

NSAID-Induced Enteropathy Affects Regulation of Hepatic Glucose Production by Decreasing GLP-1 Secretion.

BACKGROUND/AIM: Given their widespread use and their notorious effects on the lining of gut cells, including the enteroendocrine cells, we explored if chronic exposure to non-steroidal anti-inflammatory drugs (NSAIDs) affects metabolic balance in a mouse model of NSAID-induced enteropathy. METHOD: We administered variable NSAIDs to C57Blk/6J mice through intragastric gavage and measured their energy balance, glucose hemostasis, and GLP-1 levels. We treated them with Exendin-9 and Exendin-4 and ran a euglycemic-hyperinsulinemic clamp. RESULTS: Chronic administration of multiple NSAIDs to C57Blk/6J mice induces ileal ulcerations and weight loss in animals consuming a high-fat diet. Despite losing weight, NSAID-treated mice exhibit no improvement in their glucose tolerance. Furthermore, glucose-stimulated (glucagon-like peptide -1) GLP-1 is significantly attenuated in the NSAID-treated groups. In addition, Exendin-9-a GLP-1 receptor antagonist-worsens glucose tolerance in the control group but not in the NSAID-treated group. Finally, the hyper-insulinemic euglycemic clamp study shows that endogenous glucose production, total glucose disposal, and their associated insulin levels were similar among an ibuprofen-treated group and its control. Exendin-4, a GLP-1 receptor agonist, reduces insulin levels in the ibuprofen group compared to their controls for the same glucose exchange rates. CONCLUSIONS: Chronic NSAID use can induce small intestinal ulcerations, which can affect intestinal GLP-1 production, hepatic insulin sensitivity, and consequently, hepatic glucose production.

Gut Microbiota Represent a Major Thermogenic Biomass.

Evidence supports various roles for microbial metabolites in the control of multiple aspects of host energy flux including feeding behaviors, digestive efficiency, and energy expenditure, but few studies have quantified the energy utilization of the biomass of the gut microbiota itself. Because gut microbiota exist in an anoxic environment, energy flux is expected to be anaerobic; unfortunately, commonly utilized O2/CO2 respirometry-based approaches are unable to detect anaerobic energy flux. To quantify the contribution of the gut microbial biomass to whole-animal energy flux, we examined the effect of surgical reduction of gut biomass in C57BL/6J mice via cecectomy and assessed energy expenditure using methods sensitive to anaerobic flux, including bomb and direct calorimetry. First, we determined that cecectomy caused an acceleration of weight gain over several months due to a reduction in combined total host plus microbial energy expenditure, as reflected by an increase in energy efficiency (ie, weight gained per calorie absorbed). Second, we determined that under general anesthesia, cecectomy caused immediate changes in heat dissipation that were significantly modified by short-term pretreatment with dietary or pharmaceutical interventions known to modify the microbiome, and confirmed that these effects were undetectable by respirometry. We conclude that while the cecum only contributes approximately 1% of body mass in the mouse, this organ contributes roughly 8% of total resting energy expenditure, that this contribution is predominantly anaerobic, and that the composition and abundance of the cecal microbial contents can significantly alter its contribution to energy flux.

Case of relapsing sulfasalazine-induced hypersensitivity syndrome upon re-exposure.

Sulfasalazine-induced hypersensitivity syndrome (SIHS) is a serious systemic delayed adverse drug reaction that is associated with significant morbidity and mortality. Here, we report the first case, to our knowledge, of a patient with previously unidentified SIHS who developed a significantly more rapid and extreme recurrence on re-exposure to sulfasalazine. The patient is a 58-year-old woman with asymptomatic Crohn's disease who, 10 days after initiating sulfasalazine, developed fevers, diffuse rash, pancytopenia, hypotension and hepatitis without a definitive source of infection. Sixteen days after her first hospitalisation, she was restarted on sulfasalazine and was readmitted within 10 hours with a similar but more serious presentation, requiring vasopressors. She did recover completely without any further recurrence to date, after definitively discontinuing sulfasalazine. This case demonstrates the importance of recognising SIHS early in patients to prevent re-exposure to sulfasalazine and to ensure timely initiation of appropriate treatment.

Endocannabinoid Receptor-1 and Sympathetic Nervous System Mediate the Beneficial Metabolic Effects of Gastric Bypass.

The exact mechanisms underlying the metabolic effects of bariatric surgery remain unclear. Here, we demonstrate, using a combination of direct and indirect calorimetry, an increase in total resting metabolic rate (RMR) and specifically anaerobic RMR after Roux-en-Y gastric bypass (RYGB), but not sleeve gastrectomy (SG). We also show an RYGB-specific increase in splanchnic sympathetic nerve activity and "browning" of visceral mesenteric fat. Consequently, selective splanchnic denervation abolishes all beneficial metabolic outcomes of gastric bypass that involve changes in the endocannabinoid signaling within the small intestine. Furthermore, we demonstrate that administration of rimonabant, an endocannabinoid receptor-1 (CB1) inverse agonist, to obese mice mimics RYGB-specific effects on energy balance and splanchnic nerve activity. On the other hand, arachidonoylethanolamide (AEA), a CB1 agonist, attenuates the weight loss and metabolic signature of this procedure. These findings identify CB1 as a key player in energy regulation post-RYGB via a pathway involving the sympathetic nervous system.

Transcriptional Basis for Rhythmic Control of Hunger and Metabolism within the AgRP Neuron.

The alignment of fasting and feeding with the sleep/wake cycle is coordinated by hypothalamic neurons, though the underlying molecular programs remain incompletely understood. Here, we demonstrate that the clock transcription pathway maximizes eating during wakefulness and glucose production during sleep through autonomous circadian regulation of NPY/AgRP neurons. Tandem profiling of whole-cell and ribosome-bound mRNAs in morning and evening under dynamic fasting and fed conditions identified temporal control of activity-dependent gene repertoires in AgRP neurons central to synaptogenesis, bioenergetics, and neurotransmitter and peptidergic signaling. Synaptic and circadian pathways were specific to whole-cell RNA analyses, while bioenergetic pathways were selectively enriched in the ribosome-bound transcriptome. Finally, we demonstrate that the AgRP clock mediates the transcriptional response to leptin. Our results reveal that time-of-day restriction in transcriptional control of energy-sensing neurons underlies the alignment of hunger and food acquisition with the sleep/wake state.

Total pancreatectomy with islet cell transplantation vs intrathecal narcotic pump infusion for pain control in chronic pancreatitis.

AIM: To evaluate pain control in chronic pancreatitis patients who underwent total pancreatectomy with islet cell transplantation or intrathecal narcotic pump infusion. METHODS: We recognized 13 patients who underwent intrathecal narcotic pump (ITNP) infusion and 57 patients who underwent total pancreatectomy with autologous islet cell transplantation (TP + ICT) for chronic pancreatitis (CP) pain control between 1998 and 2008 at Indiana University Hospital. All patients had already failed multiple other modalities for pain control and the decision to proceed with either intervention was made at the discretion of the patients and their treating physicians. All patients were evaluated retrospectively using a questionnaire inquiring about their pain control (using a 0-10 pain scale), daily narcotic dose usage, and hospital admission days for pain control before each intervention and during their last follow-up. RESULTS: All 13 ITNP patients and 30 available TP + ICT patients were evaluated. The mean age was approximately 40 years in both groups. The median duration of pain before intervention was 6 years and 7 years in the ITNP and TP + ICT groups, respectively. The median pain score dropped from 8 to 2.5 (on a scale of 0-10) in both groups on their last follow up. The median daily dose of narcotics also decreased from 393 mg equivalent of morphine sulfate to 8 mg in the ITNP group and from 300 mg to 40 mg in the TP + ICT group. No patient had diabetes mellitus (DM) before either procedure whereas 85% of those who underwent pancreatectomy were insulin dependent on their last evaluation despite ICT. CONCLUSION: ITNP and TP + ICT are comparable for pain control in patients with CP however with high incidence of DM among those who underwent TP + ICT. Prospective comparative studies and longer follow up are needed to better define treatment outcomes.

Leptin Is Required for Glucose Homeostasis after Roux-en-Y Gastric Bypass in Mice.

BACKGROUND & AIMS: Leptin, the protein product of the ob gene, increases energy expenditure and reduces food intake, thereby promoting weight reduction. Leptin also regulates glucose homeostasis and hepatic insulin sensitivity via hypothalamic proopiomelanocortin neurons in mice. Roux-en-Y gastric bypass (RYGB) induces weight loss that is substantial and sustained despite reducing plasma leptin levels. In addition, patients who fail to undergo diabetes remission after RYGB are hypoletinemic compared to those who do and to lean controls. We have previously demonstrated that the beneficial effects of RYGB in mice require the melanocortin-4 receptor, a downstream effector of leptin action. Based on these observations, we hypothesized that leptin is required for sustained weight reduction and improved glucose homeostasis observed after RYGB. METHODS: To investigate this hypothesis, we performed RYGB or sham operations on leptin-deficient ob/ob mice maintained on regular chow. To investigate whether leptin is involved in post-RYGB weight maintenance, we challenged post-surgical mice with high fat diet. RESULTS: RYGB reduced total body weight, fat and lean mass and caused reduction in calorie intake in ob/ob mice. However, it failed to improve glucose tolerance, glucose-stimulated plasma insulin, insulin tolerance, and fasting plasma insulin. High fat diet eliminated the reduction in calorie intake observed after RYGB in ob/ob mice and promoted weight regain, although not to the same extent as in sham-operated mice. We conclude that leptin is required for the effects of RYGB on glucose homeostasis but not body weight or composition in mice. Our data also suggest that leptin may play a role in post-RYGB weight maintenance.