Adipose Tissue Storage in the Rapid Remission of Hepatic and Cardiac Metabolic Dysfunction After Bariatric Surgery (CB5)

Adipose Tissue Storage in the Rapid Remission of Hepatic and Cardiac Metabolic Dysfunction After Bariatric Surgery

Improved Adipose Tissue Storage of Dietary Fatty Acids as a New Mechanism for the Rapid Remission of Hepatic and Cardiac Metabolic Dysfunction After Bariatric Surgery

Institut universitaire de cardiologie et de pneumologie de Québec, University Laval, Centre de recherche du Centre hospitalier universitaire de Sherbrooke

The present protocol aims to understand and establish whether there is a causal link between adipose tissue metabolic remodeling and Type 2 Diabetes (T2D) remission after bariatric surgery. All participants will have a bariatric surgery, divided in 2 groups: with or without T2D.

This clinical assay will include 5 visits: the screening visit and four 9-hour postprandial metabolic sessions (A0, A1, B0 and C0) before and after surgery: initial visit: screening before surgery: 2 metabolic sessions A0 and A1 (without/with niacin) will be performed, in random order, at least one week interval. 12 days post surgery: 1 metabolic session B0 (without niacin) 1 year post surgery: 1 metabolic session C0 (without niacin) Each metabolic visit will last 9 hours with: perfusion of stable tracers, ingestion of a liquid meal Positron-Emitting-Tomography (PET) acquisitions using radiopharmaceuticals such as [18F]-fluoro-6-thia-heptadecanoic acid ([18F]-FTHA) and [11C]-palmitate, MRI acquisitions.[18F]fluoro-6-thia-heptadecanoic acid (FTHA). The niacin will be given during metabolic visits A1 as a regulator of lipids metabolism. During these visits, the subjects will ingest 150mg every half hour for 6 hours. Niacin will be used as a pharmacological suppressor of dietary fatty acid (DFA) spillover in order to determine the role played by this mechanism in the reduction of postprandial endogen glucose production (EGP) in T2D after bariatric surgery.

It will be a randomized crossover study prior to bariatric surgery (visits A0 and A1) followed by a longitudinal follow-up study after surgery (visits B0 and C0) in two groups (type 2 diabetes vs. controls). Inside each group, the protocol will be carried out as a within-subject, in which each subject will serve as his/her own control.

Change in liver non-esterified fatty acid (NEFA) uptake, oxidation, esterification and secretion into very low-density lipoprotein (VLDL).

calculated from i.v. and oral stable isotope tracers (mass spectrometry) incorporated into triglyceride-rich lipoproteins and NEFA.

Inclusion Criteria: Aged 18 to 65 BMI 35 kg/m2 Diagnosed T2D - according to Diabetes Canada diagnostics criteria. Diagnosed non-T2D - according to Diabetes Canada diagnostics criteria. Women with a negative serum pregnancy test. Exclusion Criteria: Treatment with an oral contraceptive; Treatment with fibrate, thiazolidinedione, insulin, or beta-blocker, drugs that affect metabolism and cannot be stopped temporarily or which have long-lasting effects; Presence of overt cardiovascular disease, liver or renal failure or other uncontrolled medical conditions; Any other contraindication to surgery or to temporarily suspending current medications for diabetes, lipids or hypertension; Smoking or consumption of more than 2 alcoholic beverages per day; Any contraindication to MRI; A Diabetes Remission (DiaRem) score >8 (low probability of T2D remission); Having participated to a research study with exposure to radiation in the last two years before the start of the study; Pregnant or breastfeeding women; Patients weighing more than 200 kg to respect the weight and gantry limit of our MRI and PET/CT scanners. Being allergic to eggs