Marwa Abu El Haija

All Publications

• Gastric bypass alters diurnal feeding behavior and reprograms hepatic clock to regulate endogenous glucose flux. JCI insight Ye, Y., Abu El Haija, M., Obeid, R., Herz, H., Tian, L., Linden, B., Chu, Y., Guo, D. F., Levine, D. C., Cedernaes, J., Rahmouni, K., Bass, J., Mokadem, M. 2023

  Abstract

  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 its effects on the molecular clock, and its requirement for the metabolic effects of this bariatric procedure in obese mice. We find that RYGB reverses the high fat diet-induced disruption in diurnal eating pattern during the early post-surgery 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 ZT2), but not the "feeding" phase (ZT14). Using a clock gene reporter mouse model (mPer2Luc), we reveal that RYGB induces a liver-specific phase shift in peripheral clock oscillation with no changes to the central clock activity within the suprachiasmatic nucleus (SCN). In addition, we show that weight loss effects are attenuated in obese ClockDelta19 mutant mice post-RYGB that also fail 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.

  View details for DOI 10.1172/jci.insight.166618

  View details for PubMedID 36787197

• Changes in Resting Energy Expenditure After Sleeve Gastrectomy: a Review of the Literature. Obesity surgery Abu El Haija, M., Kohli, R. 2022

  Abstract

  Obesity is a rising medical condition; metabolic and bariatric surgery, mainly sleeve gastrectomy, offers a successful weight loss option which is maintainable. Weight loss is heavily dependent on energy expenditure. Resting energy expenditure (REE) after sleeve gastrectomy has been described in the literature with varying results. In this review, we review all published literature that described REE post sleeve gastrectomy in human. We found that REE goes down after sleeve gastrectomy as the weight loss occurs and REE when adjusted for weight (REE/kg) only goes up significantly in the 2 studies that included youths. REE/kg did not significantly change in studies including adults ages 30 and above. This study is the first that reviews and summarized REE findings post sleeve gastrectomy and more studies are needed especially targeting the pediatric and youth populations.

  View details for DOI 10.1007/s11695-022-06092-y

  View details for PubMedID 35503157

• Stemming the Tide of Gastrointestinal Chronic Granulomatous Disease. Digestive diseases and sciences Cagil, Y., Tong, E., Guimaraes, C., Andrews, J., Abu El Haija, M., Triadafilopoulos, G., Yeh, A. M., Shah, A. 2022

  View details for DOI 10.1007/s10620-022-07492-x

  View details for PubMedID 35397696

• Toll-like receptor 4 and myeloid differentiation factor 88 are required for gastric bypass-induced metabolic effects. Surgery for obesity and related diseases : official journal of the American Society for Bariatric Surgery Abu El-Haija, M., Ye, Y., Chu, Y., Herz, H., Linden, B., Shahi, S. K., Zarei, K., Mangalam, A. K., Mcelroy, S. J., Mokadem, M. 2021

  Abstract

  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 naive 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 likelymediated by gut microbiome.

  View details for DOI 10.1016/j.soard.2021.07.019

  View details for PubMedID 34462225

• Experience With Vertical Sleeve Gastrectomy in Adolescent and Young Adult Ehlers-Danlos Syndrome Patients: a Case Series and Review of the Literature Obesity Surgery Herdes, R. E., Abu El Haija, M., Johnson, K., Shepard, W., Zak, Y., Bruzoni, M., Pratt, J. S. 2021

  View details for DOI 10.1007/s11695-021-05453-3

• The Immediate Impact of the Novel Coronavirus (COVID-19) Pandemic on Adolescents with Severe Obesity – Another Pandemic Asploro Journal of Pediatrics and Child Health Matheson, B. E., Herdes, R. E., Garza, D., Shepard, W. E., Bruzoni, M., Pratt, J. S., Abu El Haija, M. 2021
• Considerations on the role of esophagogastroduodenoscopy in the pediatric metabolic and bariatric surgery patient Surgery for Obesity and Related Diseases Abu EL Haija, M., Browne, N. T., Griggs, C. L., Herdes, R. E., Michalsky, M. P., Ogle, S. B., Zitsman, J. L., Pratt, J. S. 2021

  View details for DOI 10.1016/j.soard.2021.07.010

• NSAID-Induced Enteropathy Affects Regulation of Hepatic Glucose Production by Decreasing GLP-1 Secretion Nutrients Herz, H., Song, Y., Ye, Y., Tian, L., Linden, B., Abu El Haija, M., Chu, Y., Grobe, J., Lengeling, R., Mokadem, M. 2021; 14 (1): 120

  View details for DOI 10.3390/nu14010120

• Endocannabinoid Receptor-1 and Sympathetic Nervous System Mediate the Beneficial Metabolic Effects of Gastric Bypass. Cell reports Ye, Y. n., Abu El Haija, M. n., Morgan, D. A., Guo, D. n., Song, Y. n., Frank, A. n., Tian, L. n., Riedl, R. A., Burnett, C. M., Gao, Z. n., Zhu, Z. n., Shahi, S. K., Zarei, K. n., Couvelard, A. n., Poté, N. n., Ribeiro-Parenti, L. n., Bado, A. n., Noureddine, L. n., Bellizzi, A. n., Kievit, P. n., Mangalam, A. K., Zingman, L. V., Le Gall, M. n., Grobe, J. L., Kaplan, L. M., Clegg, D. n., Rahmouni, K. n., Mokadem, M. n. 2020; 33 (4): 108270

  Abstract

  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.

  View details for DOI 10.1016/j.celrep.2020.108270

  View details for PubMedID 33113371

• Commentary: Children with Gastroesophageal Reflux Disease Consume More Calories and Fat than Controls. Journal of pediatric gastroenterology and nutrition Abu El Haija, M. n., Agostoni, C. n. 2020

  View details for DOI 10.1097/MPG.0000000000002656

  View details for PubMedID 32079981

• Intraoperative Liver Biopsy During Adolescent Bariatric Surgery: Is It Really Necessary? Obesity surgery Jones, R. E., Yeh, A. M., Kambham, N., El Haija, M. A., Pratt, J., Bruzoni, M. 2019

  Abstract

  BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is prevalent in children with obesity and is definitively diagnosed with liver biopsy. However, the utility of routine biopsy during adolescent bariatric surgery remains unknown. We describe the usefulness of routine versus selective intraoperative liver biopsy in adolescents undergoing bariatric surgery.METHODS: A retrospective review of adolescents who received bariatric surgery at our institution between 2007 and 2018 was performed. Prior to 2014, all patients routinely received intraoperative liver biopsy. After 2014, biopsy was performed selectively on an individual basis for transaminitis or clinical concern. Demographic, biochemical, and histopathologic data were compared between patients who underwent routine, selective, or no biopsy.RESULTS: There were 77 patients who received bariatric surgery during the study period: 32 underwent routine biopsy, 13 selective biopsy, and 32 no biopsy. Selective liver biopsy was more likely to show pathologic evidence of fibrosis (84.6% versus 31.2%, p=0.000) and steatosis (100.0% versus 59.4%, p=0.003), and higher mean NAFLD activity score compared with routine biopsies (4.4 versus 2.1, p=0.001). Patients with steatosis had significantly higher preoperative fasting insulin (41.4 versus 21.1mIU/L, p=0.000), and patients with fibrosis had significantly higher glycated hemoglobin (6.1% versus 5.5%, p=0.033) and alanine aminotransferase (81.5 versus 52.7mg/dL, p=0.043). There were no biopsy complications or changes in management due to biopsy results.CONCLUSIONS: Routine intraoperative liver biopsy during adolescent bariatric surgery possesses questionable benefit, as it does not appear to impact short-term postoperative management. Prospective, longitudinal studies are needed to better understand the meaningfulness of liver histopathology in this population.

  View details for DOI 10.1007/s11695-019-04136-4

  View details for PubMedID 31446562

• Diagnosis and management of children with Blue Rubber Bleb Nevus Syndrome: A multi-center case series. Digestive and liver disease : official journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver Isoldi, S., Belsha, D., Yeop, I., Uc, A., Zevit, N., Mamula, P., Loizides, A. M., Tabbers, M., Cameron, D., Day, A. S., Abu-El-Haija, M., Chongsrisawat, V., Briars, G., Lindley, K. J., Koeglmeier, J., Shah, N., Harper, J., Syed, S. B., Thomson, M. 2019

  Abstract

  BACKGROUND: Blue Rubber Bleb Nevus Syndrome (BRBNS) is a rare, severe, sporadically occurring disorder characterized by multiple venous malformations.AIMS: To present and analyze a case series of pediatric patients with BRBNS and to describe diagnostic approaches and management options applied.PATIENTS AND METHODS: Multicenter, retrospective study, evaluating the diagnosis and management of children with BRBNS.RESULTS: Eighteen patients diagnosed with BRBNS were included. Cutaneous venous malformations were observed in 78% and gastrointestinal venous malformations in 89%. Lesions were also found in other organs including muscles, joints, central nervous system, eyes, parotid gland, spine, kidneys and lungs. Gastrointestinal lesions were more common in the small intestine than in stomach or colon. The management varied significantly among centers. Endoscopic therapy and surgical therapy alone failed to prevent recurrence of lesions. In younger children and in patients with musculoskeletal or other organ involvement, sirolimus was used with 100% success rate in our series (5 patients treated) although poor compliance with subtherapeutic sirolimus trough levels led to recurrence in a minority.CONCLUSIONS: Considering the multi-organ involvement in BRBNS, diagnosis and management requires a multidisciplinary approach. The treatment includes conservative, medical, endoscopic and surgical options. Prospective multicenter studies are needed to identify the optimal management of this rare condition.

  View details for DOI 10.1016/j.dld.2019.04.020

  View details for PubMedID 31358484

• Incidental finding of a huge ovarian serous cystadenoma in an adolescent female with menorrhagia SAGE OPEN MEDICAL CASE REPORTS Abu Sulb, A., Abu El Haija, M., Muthukumar, A. 2016; 4: 2050313X16645755

  Abstract

  Pelvic tumors in adolescent females are very uncommon. While the most common presentation is pelvic discomfort, we report the case of a 14-year-old female presenting with menorrhagia which is an unusual initial complaint for a large pelvic tumor. Adolescent females who present with heavy menstrual bleeding initially undergo assessment to rule out a bleeding disorder. In this case, careful history and physical examination helped in making a quick diagnosis and management. Ultrasound of abdomen showed a huge cystic mass due to serous cystadenoma of the ovary.

  View details for DOI 10.1177/2050313X16645755

  View details for Web of Science ID 000443420000009

  View details for PubMedID 27489715

  View details for PubMedCentralID PMC4927290

• Glycaemic regulation and insulin secretion are abnormal in cystic fibrosis pigs despite sparing of islet cell mass CLINICAL SCIENCE Uc, A., Olivier, A. K., Griffin, M. A., Meyerholz, D. K., Yao, J., Abu-El-Haija, M., Buchanan, K. M., Calderon, O., Abu-El-Haija, M., Pezzulo, A. A., Reznikov, L. R., Hoegger, M. J., Rector, M. V., Ostedgaard, L. S., Taft, P. J., Gansemer, N. D., Ludwig, P. S., Hornick, E. E., Stoltz, D. A., Ode, K. L., Welsh, M. J., Engelhardt, J. F., Norris, A. W. 2015; 128 (2): 131–42

  Abstract

  Diabetes is a common and significant co-morbidity in cystic fibrosis (CF). The pathogenesis of cystic fibrosis related diabetes (CFRD) is incompletely understood. Because exocrine pancreatic disease is similar between humans and pigs with CF, the CF pig model has the potential to contribute significantly to the understanding of CFRD pathogenesis. We determined the structure of the endocrine pancreas in fetal, newborn and older CF and non-CF pigs and assessed endocrine pancreas function by intravenous glucose tolerance test (IV-GTT). In fetal pigs, pancreatic insulin and glucagon density was similar between CF and non-CF. In newborn and older pigs, the insulin and glucagon density was unchanged between CF and non-CF per total pancreatic area, but increased per remnant lobular tissue in CF reflecting exocrine pancreatic loss. Although fasting glucose levels were not different between CF and non-CF newborns, CF newborns demonstrated impaired glucose tolerance and increased glucose area under the curve during IV-GTT. Second phase insulin secretion responsiveness was impaired in CF newborn pigs and significantly lower than that observed in non-CF newborns. Older CF pigs had elevated random blood glucose levels compared with non-CF. In summary, glycaemic abnormalities and insulin secretion defects were present in newborn CF pigs and spontaneous hyperglycaemia developed over time. Functional changes in CF pig pancreas were not associated with a decline in islet cell mass. Our results suggest that functional islet abnormalities, independent of structural islet loss, contribute to the early pathogenesis of CFRD.

  View details for DOI 10.1042/CS20140059

  View details for Web of Science ID 000349363600006

  View details for PubMedID 25142104

  View details for PubMedCentralID PMC4346161

• Dyserythropoiesis in a child with pyruvate kinase deficiency and coexistent unilateral multicystic dysplastic kidney PEDIATRIC BLOOD & CANCER Abu El Haija, M., Qian, Y., Muthukumar, A. 2014; 61 (8): 1463–65

  Abstract

  Pyruvate kinase (PK) deficiency is the commonest enzyme deficiency in the glycolytic pathway leading to hemolytic anemia secondary to decreased Adenosine Triphosphate (ATP) synthesis in the red cells. synthesis. PK deficiency due to mutations in the PKLR (1q21) gene leads to highly variable clinical presentation ranging from severe fetal anemia to well compensated anemia in adults. We describe dyserythropoiesis in the bone marrow of a child with transfusion dependent anemia and unilateral multicystic dysplastic kidney (MCDK) mimicking Congenital Dyserythropoietic Anemia type I (CDA type I). Persistently low erythrocyte PK levels and double heterozygous mutations present in the PKLR gene confirmed the diagnosis of PK deficiency.

  View details for DOI 10.1002/pbc.24953

  View details for Web of Science ID 000337698600025

  View details for PubMedID 24481986

• Pancreatic and biliary secretion are both altered in cystic fibrosis pigs AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY Uc, A., Giriyappa, R., Meyerholz, D. K., Griffin, M., Ostedgaard, L. S., Tang, X., Abu-El-Haija, M., Stoltz, D. A., Ludwig, P., Pezzulo, A., Abu-El-Haija, M., Taft, P., Welsh, M. J. 2012; 303 (8): G961–G968

  Abstract

  The pancreas, liver, and gallbladder are commonly involved in cystic fibrosis (CF), and acidic, dehydrated, and protein-rich secretions are characteristic findings. Pancreatic function studies in humans have been done by sampling the jejunal fluid. However, it has been difficult to separately study the function of pancreatic and biliary systems in humans with CF, because jejunal fluid contains a mixture of bile and pancreatic fluids. In contrast, pancreatic and biliary ducts open separately into the porcine intestine; therefore, biliary and pancreatic fluid can be individually analyzed in CF pigs. We studied newborn wild-type (WT) and CF pigs and found that CFTR was localized to the pancreatic ducts. We collected bile and pancreatic fluid and analyzed pancreatic enzymes with activity assays and immunoblot. Pancreatic enzyme expression was significantly decreased in CF compared with WT pigs. The volume and pH of pancreatic fluid were significantly lower and protein concentration was >5-fold higher in CF pigs. Secretin stimulation increased pancreatic fluid volume and pH in WT, but not CF, pigs. Baseline bile volume did not differ between WT and CF pigs, but volume did not increase in response to secretin in CF pigs. Bile pH was lower and protein concentration was twofold higher in CF pigs. These results indicate that pancreatic and biliary secretions are altered in CF pigs. Abnormal pancreatic and biliary secretion in CF may have important implications in disease pathogenesis.

  View details for DOI 10.1152/ajpgi.00030.2012

  View details for Web of Science ID 000309980500008

  View details for PubMedID 22936270

  View details for PubMedCentralID PMC3469695

• Pancreatic Damage in Fetal and Newborn Cystic Fibrosis Pigs Involves the Activation of Inflammatory and Remodeling Pathways AMERICAN JOURNAL OF PATHOLOGY Abu-El-Haija, M., Ramachandran, S., Meyerholz, D. K., Abu-El-Haija, M., Griffin, M., Giriyappa, R. L., Stoltz, D. A., Welsh, M. J., McCray, P. B., Uc, A. 2012; 181 (2): 499–507

  Abstract

  Pancreatic disease has onset in utero in humans with cystic fibrosis (CF), and progresses over time to complete destruction of the organ. The exact mechanisms leading to pancreatic damage in CF are incompletely understood. Inflammatory cells are present in the pancreas of newborn pigs with CF (CF pigs) and humans, which suggests that inflammation may have a role in the destructive process. We wondered whether tissue inflammation and genes associated with inflammatory pathways were increased in the pancreas of fetal CF pigs [83 to 90 days gestation (normal pig gestation is ~114 days)] and newborn pigs. Compared with fetal pigs without CF (non-CF pigs), in fetal CF pigs, the pancreas exhibited patchy inflammation and acinar atrophy, with progression in distribution and severity in neonatal CF pigs. Large-scale transcript profiling revealed that the pancreas in fetal and newborn CF pigs exhibited significantly increased expression of proinflammatory, complement cascade, and profibrotic genes when compared with fetal and newborn non-CF pigs. Acinar cells exhibited increased apoptosis in the pancreas of fetal and newborn CF pigs. α-Smooth muscle actin and transforming growth factor β1 were increased in both fetal and newborn CF pig pancreas, suggesting activation of profibrotic pathways. Cell proliferation and mucous cell metaplasia were detected in newborn, but not fetal, CF pigs, indicating that they were not an initiator of pathogenesis but a response. Proinflammatory, complement cascade, proapoptotic, and profibrotic pathways are activated in CF pig pancreas, and likely contribute to the destructive process.

  View details for DOI 10.1016/j.ajpath.2012.04.024

  View details for Web of Science ID 000307141800015

  View details for PubMedID 22683312

  View details for PubMedCentralID PMC3409440

• Simplified and versatile method for isolation of high-quality RNA from pancreas BIOTECHNIQUES Griffin, M., Abu-El-Haija, M., Abu-El-Haija, M., Rokhlina, T., Uc, A. 2012; 52 (5): 332–34

  Abstract

  Isolation of high-quality RNA from pancreas is challenging because the organ contains large quantities of RNases and undergoes autolysis upon harvest. Here we present a simplified perfusion method of the pancreas using an RNase inhibitor. The technique consistently yields high-quality RNA from stored pancreas samples suitable for molecular biology applications, including quantitative RT-PCR. Yields are comparable to RNA isolated from pancreas immediately, but superior to RNA isolated from stored samples that were snap-frozen or immersed in an RNase inhibitor solution. In addition, when compared to the previously reported in situ ductal perfusion technique, our method does not cause histological artifacts.

  View details for DOI 10.2144/0000113862

  View details for Web of Science ID 000304577000009

  View details for PubMedID 22578126

  View details for PubMedCentralID PMC3738267