Lipid absorption and overall intestinal lymphatic transport are impaired following partial small bowel resection in mice

Short bowel syndrome (SBS) is associated with diminished levels of serum fats caused by unknown mechanisms. We have shown that mesenteric lymphatics remodel to a more primitive state one week after small bowel resection (SBR); therefore, this study focuses on the effect of chronic lymphatic remodeling and magnitude of resection on intestinal fatty acid uptake and transport. C57BL6 and Prox1 creER-Rosa26LSLTdTomato (lymphatic reporter) mice underwent 50% or 75% proximal SBR or sham operations. Functional transport of lipids and fecal fat content was measured and lymphatic vasculature was compared via imaging. There was a significant reduction in functional transport of cholesterol and triglyceride after SBR with increasing loss of bowel, mirrored by a progressive increase in fecal fat content. We also describe significant morphological changes in the lymphatic vasculature in both the lamina propria and mesentery. Intestinal lymphatic drainage assay in vivo demonstrated a marked reduction of systemic absorption after resection. Intestinal lymphatic vessels significantly remodel in the setting of chronic SBS. This remodeling results in impaired intestinal transport of fat via the compromised lymphatic architecture, contributing to decreased fatty acid uptake. We believe that these changes may contribute to the development of IFALD, a major morbidity in patients with SBS.

727 EXOCRINE PANCREATIC INSUFFICIENCY AFTER ESOPHAGECTOMY: A SYSTEMATIC REVIEW OF LITERATURE

Complaints of maldigestion, malabsorption, and unintended weight loss after esophagectomy are often attributed to an impaired exocrine pancreatic function. This review systematically summarizes all literature reporting on the presence of exocrine pancreatic insufficiency (EPI) after esophagectomy and the effect of treatment with pancreatic enzymes on gastrointestinal complaints, body weight, and quality of life. Methods Databases of PubMed, Embase, and Wiley/Cochrane Library were searched systematically until July 2020. Studies reporting on EPI and pancreatic enzyme replacement therapy after esophagectomy were included. Results Four studies, including 158 patients, were selected. Exocrine pancreatic function was investigated in three studies, measured by fecal elastase-1 and 72-hour fecal fat excretion. Fecal elastase-1 levels <200 μg/g were reported in 16% of patients at 4 months, 18% at 6 months, and 31% at 18-24 months postoperatively. A decreased fecal fat absorption was noticed in 57% 1 month postoperatively. Treatment with pancreatic enzymes was reported in two studies. In patients with fecal elastase-1 levels <200 μg/g, 90% of patients reported improvement in symptoms and 70% reported improvement in weight. In patients with complaints of steatorrhea, 87% noticed settlement of symptoms. Conclusion Based on current literature, complaints of maldigestion, malabsorption, and unintended weight loss after esophagectomy are common and can be related to an impaired exocrine pancreatic function. High-quality studies evaluating the presence of EPI and the effect of treatment with pancreatic enzymes after esophagectomy are needed to verify this conclusion.

Exocrine pancreatic insufficiency after esophagectomy: a systematic review of literature

Summary Complaints of maldigestion, malabsorption, and unintended weight loss after esophagectomy are often attributed to an impaired exocrine pancreatic function. This review systematically summarizes all literature reporting on the presence of exocrine pancreatic insufficiency (EPI) after esophagectomy and the effect of treatment with pancreatic enzymes on gastrointestinal complaints, body weight, and quality of life. Databases of PubMed, Embase, and Wiley/Cochrane Library were searched systematically until July 2020. Studies reporting on EPI and pancreatic enzyme replacement therapy after esophagectomy were included. The Newcastle–Ottawa scale was used to assess study quality. Four studies, including 158 patients, were selected. The maximum score for study quality was six (range 4–6). Exocrine pancreatic function was investigated in three studies, measured by fecal elastase-1 and 72-hour fecal fat excretion. Fecal elastase-1 levels <200 μg/g were reported in 16% of patients at 4 months, 18% at 6 months, and 31% at 18–24 months postoperatively. A decreased fecal fat absorption was noticed in 57% 1 month postoperatively. Treatment with pancreatic enzymes was reported in two studies. In patients with fecal elastase-1 levels <200 μg/g, 90% of patients reported improvement in symptoms and 70% reported improvement in weight. In patients with complaints of steatorrhea, 87% noticed settlement of symptoms. Based on current literature, complaints of maldigestion, malabsorption, and unintended weight loss after esophagectomy are common and can be related to an impaired exocrine pancreatic function. High-quality studies evaluating the presence of EPI and the effect of treatment with pancreatic enzymes after esophagectomy are needed to verify this conclusion.

NT-PGC-1α deficiency attenuates high-fat diet-induced obesity by modulating food intake, fecal fat excretion and intestinal fat absorption

Transcriptional coactivator PGC-1α and its splice variant NT-PGC-1α regulate metabolic adaptation by modulating many gene programs. Selective ablation of PGC-1α attenuates diet-induced obesity through enhancing fatty acid oxidation and thermogenesis by upregulation of NT-PGC-1α in brown adipose tissue (BAT). Recently, we have shown that selective ablation of NT-PGC-1α reduces fatty acid oxidation in BAT. Thus, the objective of this study was to test our hypothesis that NT-PGC-1α−/− mice would be more prone to diet-induced obesity. Male and female NT-PGC-1α+/+ (WT) and NT-PGC-1α−/− mice were fed a regular chow or 60% high-fat (HF) diet for 16 weeks. Contrary to our expectations, both male and female NT-PGC-1α−/− mice fed HFD were protected from diet-induced obesity, with more pronounced effects in females. This lean phenotype was primarily driven by reduced dietary fat intake. Intriguingly, HFD-fed female, but not male, NT-PGC-1α−/− mice further exhibited decreased feed efficiency, which was closely associated with increased fecal fat excretion and decreased uptake of fatty acids by the intestinal enterocytes and adipocytes with a concomitant decrease in fatty acid transporter gene expression. Collectively, our results highlight the role for NT-PGC-1α in regulating whole body lipid homeostasis under HFD conditions.

Potato Fibers Have Positive Effects on Subjective Appetite Sensations in Healthy Men, but Not on Fecal Fat Excretion: A Randomized Controlled Single-Blind Crossover Trial

Dietary fibers can affect appetite and gut metabolism, but the effect of the novel potato fibers FiberBind and rhamnogalacturonan I (RG-I) is unknown. We, therefore, aimed to investigate the effect of daily intake of FiberBind and RG-I on appetite sensations and fecal fat excretion. In a single-blinded, randomized, three-way crossover trial, wheat buns with FiberBind, RG-I, or low fiber (control) were consumed by 18 healthy men during a 21-day period. Appetite sensation and blood samples during a 3 h meal test, fecal fat content, and ad libitum energy intake were assessed after each period. Compared to RG-I and control, FiberBind caused a higher composite satiety score (6% ± 2% and 5% ± 2%), lower prospective food consumption (5% ± 2% and 6% ± 2%), and lower desire to eat (7% ± 3% and 6% ± 3%) (all p < 0.05). FiberBind also caused higher satiety (6% ± 2%) and fullness (9% ± 3%) compared to RG-I (all p < 0.01). No effects on fecal fat excretion or energy intake were found. The RG-I fiber caused higher postprandial glucose concentration compared to FiberBind (p < 0.05) and higher insulin concentration at 180 min compared to control (p < 0.05). Compared to the control, RG-I and FiberBind lowered peak insulin concentration (both p < 0.05) and delayed time to peak for glucose (both p < 0.05). In conclusion, FiberBind intake could be beneficial for appetite regulation, but neither FiberBind nor RG-I affected fecal fat excretion or energy intake.

A276 TOTAL PANCREATIC LIPOMATOSIS AND EXOCRINE PANCREATIC INSUFFICIENCY IN A PATIENT WITH CELIAC DISEASE: AN UNUSUAL ENTITY

Background Exocrine pancreatic insufficiency (EPI) is characterized by maldigestion and malabsorption of nutrients and is most commonly caused by diseases of the pancreatic parenchyma including chronic pancreatitis and cystic fibrosis (CF). However, EPI is also observed in other conditions including celiac disease (CD). Aims We report a case of EPI in a patient with CD found to have total fatty replacement of the pancreas. Methods A case report and review of the literature were performed. Results Case Report: A 42-year-old man with CD on gluten-free diet (GFD) presented with a two-year history of increasing bowel frequency (4–6 times daily) and steatorrhea. Quantitative fecal fat over 72 hours confirmed fecal fat excretion of 101g/day; N &lt; 7g) and total stool weight of 3761g. Nadir weight was 67.6 kg. There was a dramatic response to pancreatic enzyme replacement therapy (PERT) with marked improvement in bowel habits and weight gain to 74.8 kg over half a year. There is no history of pancreatitis, abdominal pain or alcohol abuse. He does not smoke but drinks 1–2 units of alcohol per week at most. Family history is negative for pancreatitis and pancreatic malignancy. On examination, following PERT, the patient appeared well-developed and nourished. He did not have clinical features or biochemical evidence of fat-soluble vitamin deficiency following PERT. Anti-tTG was equivocal (7.6 U/mL; N &lt; 7 U/mL). IgG subclasses were normal. Chromogranin was mildly elevated (100mcg/L; N &lt; 94mcg/L), but gastrin (15ng/L) and 24-hour urine for 5-hydroxyindoleacetate [5-HIAA] (23umol/d) were normal. Endoscopic evaluations including upper endoscopy, colonoscopy, and capsule endoscopy demonstrated intact duodenal villous architecture without inflammation, no microscopic colitis, and no small bowel mucosal disease, respectively. CT of the abdomen revealed total fatty replacement of the pancreas with no pancreatic parenchyma (Figure 1). Sweat sodium test was positive (67 mmol/L, N &lt; 60 mmol/L) but CFTR gene sequencing was negative. There was no evidence of diabetes, hyperlipidemia, hyperferritinemia, Cushing’s syndrome, or hepatic disease on biochemical investigations. Literature Review: Total pancreatic lipomatosis (TPL), or fatty replacement of the pancreas, is a rare cause of EPI which leads to maldigestion, malabsorption, and malnutrition. The pathogenesis of TPL is poorly understood but predisposing factors include obesity, diabetes mellitus, hyperlipidemia, malnutrition, Cushing’s syndrome, hemochromatosis, chronic pancreatitis and CF. EPI can also manifest in patients with CD due to active small bowel inflammation or chronic pancreatitis. Last but not least, there appears to be higher prevalence of CD in CF patients. Conclusions Persistent steatorrhea with weight loss despite GFD in patients with CD should prompt other considerations of EPI and trial of PERT. Funding Agencies None

Elimination of 72-Hour Quantitative Fecal Fat Testing by Restriction, Laboratory Consultation, and Evaluation of Specimen Weight and Fat Globules

Background The 72-h quantitative fecal fat test has been mostly obsolete for many years. Our objective was to reduce and eliminate the use of this test, while providing suitable alternatives. Methods We assessed (2010–2016) utilization of the fecal fat test in Calgary, Central Alberta, and Southern Alberta, Canada. Alternatives were identified through literature review and consultation with gastroenterologist stakeholders. Logistic regression and ROC curves were used to characterize discrimination power of 72-h specimen weight on abnormal fat excretion. This was also examined in 91 subspecimens that were additionally tested for the presence of fat globules. Results As 69% of fecal fat tests (total, 106/year) were on adults (age ≥ 18), stakeholders agreed that adult specimens should not be tested until ordering physicians consulted with a clinical biochemist. This change reduced fecal fat testing by 81% to 20/year in 2015. The 72-h specimen weight was a significant predictor of abnormal fat excretion [P &lt; 0.001; area under curve (AUC) = 0.75–0.79, n = 115–417] in historic fecal fat data. A similar result was observed among subspecimens (AUC = 0.70), which improved when additionally considering the presence of fat globules (AUC = 0.74). Stakeholders consented to replacing fecal fat with a comparison of specimen weight to cutpoints with 80% specificity for abnormal fat excretion, and the test for fat globules. Conclusion Through stakeholder engagement, we implemented changes that eliminated 72-h quantitative fecal fat testing in a large geographic region in Alberta, Canada. Future fecal fat orders would be reflexed to an assessment of 72-h specimen weight and a qualitative test for fat globules in stool.