NDRG1 Activity in Fat Depots Is Associated With Type 2 Diabetes and Impaired Incretin Profile in Patients With Morbid Obesity

ObjectiveWe aimed to investigate insulin-, mTOR- and SGK1-dependent signaling basal states in morbidly obese patients’ fat. We analyzed the correlation between the signaling activity, carbohydrate metabolism, and incretin profiles of patients.MethodsThe omental and subcutaneous fat was obtained in patients with obesity. The omental study included 16 patients with normal glucose tolerance (NGT) and 17 patients with type 2 diabetes mellitus (T2DM); the subcutaneous study included 9 NGT patients and 12 T2DM patients. Insulin resistance was evaluated using the hyperinsulinemic euglycemic clamp test and HOMA-IR index. The oral glucose tolerance test (OGTT) for NGT patients and mixed meal tolerance test (MMTT) for T2DM patients were performed. The levels of incretins (GLP-1, GIP, oxyntomodulin) and glucagon were measured during the tests. Signaling was analyzed by Western blotting in adipose tissue biopsies.ResultsWe have shown equal levels of basal phosphorylation of insulin- and mTOR-dependent signaling in omental fat depot in NGT and T2DM obese patients. Nevertheless, pNDRG1-T346 was decreased in omental fat of T2DM patients. Correlation analysis has shown an inverse correlation of pNDRG1-T346 in omental fat and diabetic phenotype (HbA1c, impaired incretin profile (AUC GLP-1, glucagon)). Moreover, pNDRG1-T346 in subcutaneous fat correlated with impaired incretin levels among obese patients (inverse correlation with AUC glucagon and AUC GIP).ConclusionsAccording to results of the present study, we hypothesize that phosphorylation of pNDRG1-T346 can be related to impairment in incretin hormone processing. pNDRG1-T346 in adipose tissue may serve as a marker of diabetes-associated impairments of the systemic incretin profile and insulin sensitivity.

V-OG01 Minimally invasive oesophagectomy: Technique of linear stapled anastomosis

Background Several anastomotic techniques have been described when performing an oesophagectomy. Each technique has its own merits and drawbacks. The stapled side to side technique creates a widely patent anastomosis with low stricture rate. Methods This video highlights the technique adopted and developed over the last 5 years. There are several key steps that need to be adhered to, to create a reliable, robust and reproducible anastomosis. These include the orientation of the oesophagus during transection, the use of mucosal retaining sutures, the use of a 34 bougie for the oesophagotomy and the correct retraction of the conduit when performing the anastomosis. Results The anastomosis was successfully performed without complications. Check endoscopy revealed a widely patent secure join. The anastomosis typically now takes 15–18 minutes. At the end of the procedure, the conduit cap was buried under the pleura and the anastomosis wrapped in omental fat. The patient was discharged on day 10 on a low residue diet. Conclusions This technique has been adopted and developed over the last 5 years. It has proved reliable and reproducible with a low stricture rate and a very low leak rate. It is easier to perform than a total hand sewn anastomosis and permits visualisation of the luminal oesophagus prior to anastomosis.

Falcıform lıgament torsıon caused by omental hernıa through the foramen of morgagnı

Introduction: Torsion of the falciform ligament, one of the rarest causes of acute abdominal pain, often presents with pain in the right upper quadrant and epigastrium. Case Presentation: In this case, we present the computed tomography (CT) and magnetic resonance imaging (MRI) findings of torsion of the falciform ligament that occured in the presence of omental fat herniation through the foramen of Morgagni in an 88-year-old female patient who presented to the emergency department with acute epigastric pain. Conclusion: Torsion of the falciform ligament may develop secondary to omental hernia in the setting of Morgagni hernia and should be taken in consideration as one of the rarest causes of acute abdominal pain, even in elderly patients.

236 Omental Fat Torsion Masquerading Clinically as Acute Appendicitis in a Young Male Patient: A Rare Aetiology of Acute Abdomen and The Value of Diagnostic Laparoscopy

Acute abdominal pain is a common surgical presentation and acute appendicitis remains the top differential for most young adults. Omental fat torsion has emerged as a rare aetiology of an acute surgical abdomen in the younger population that closely mimics acute appendicitis in its clinical presentation. Preoperative diagnosis is extremely challenging in this age group due to the rarity of the condition and the non-specific nature of its clinical and laboratory findings, and hence most reported diagnoses were made intra-operatively. We report a case of omental fat torsion in a 22-year-old male who presented with clinical features that were highly suggestive of acute appendicitis. However, the diagnostic laparoscopy revealed a normally looking appendix and terminal ileum, with the presence of a twisted segment of the greater omentum in the right lumbar region. A laparoscopic omentectomy and a prophylactic appendectomy to prevent furture acute appendicitis were performed with an uneventful postoperative recovery. Histology confirmed omental fat infarction and a normal appendix. This reported case highlights a rare cause of right iliac fossa pain and demonstrates the value of diagnostic laparoscopy in the context of clinically suspected acute appendicitis in younger male patients. Diagnostic imaging was not deemed necessary in our patient given the strong clinical suspicion of acute appendicitis. Prompt laparoscopy led to definitive diagnosis as well as treatment and avoided the radiation exposure necessitated during a diagnostic computed tomography scan.

Extracellular vesicles derived from ascitic fluid enhance growth and migration of ovarian cancer cells

Ovarian cancer is associated with a high mortality rate due to diagnosis at advanced stages. Dissemination often occurs intraperitoneally within the ascites fluid. The microenvironment can support dissemination through several mechanisms. One potential ascites factor which may mediate dissemination are EVs or extracellular vesicles that can carry information in the form of miRNAs, proteins, lipids, and act as mediators of cellular communication. We present our observations on EVs isolated from ascitic supernatants from patients diagnosed with high grade serous ovarian carcinoma in augmenting motility, growth, and migration towards omental fat. MicroRNA profiling of EVs from malignant ascitic supernatant demonstrates high expression of miR 200c-3p, miR18a-5p, miR1246, and miR1290 and low expression of miR 100- 5p as compared to EVs isolated from benign ascitic supernatant. The migration of ovarian cancer spheroids towards omental fat is enhanced in the presence of malignant ascitic EVs. Gene expression of these cells showed increased expression of ZBED2, ZBTB20, ABCC3, UHMK1, and low expression of Transgelin and MARCKS. We present evidence that ovarian ascitic EVs increase the growth of ovarian cancer spheroids through miRNAs.

Circadian clock dysfunction in human omental fat links obesity to metabolic inflammation

To unravel the pathogenesis of obesity and its complications, we investigate the interplay between circadian clocks and NF-κB pathway in human adipose tissue. The circadian clock function is impaired in omental fat from obese patients. ChIP-seq analyses reveal that the core clock activator, BMAL1 binds to several thousand target genes. NF-κB competes with BMAL1 for transcriptional control of some targets and overall, BMAL1 chromatin binding occurs in close proximity to NF-κB consensus motifs. Obesity relocalizes BMAL1 occupancy genome-wide in human omental fat, thereby altering the transcription of numerous target genes involved in metabolic inflammation and adipose tissue remodeling. Eventually, clock dysfunction appears at early stages of obesity in mice and is corrected, together with impaired metabolism, by NF-κB inhibition. Collectively, our results reveal a relationship between NF-κB and the molecular clock in adipose tissue, which may contribute to obesity-related complications.