Brown adipose tissue in congenital generalized lipodystrophy and familial partial lipodystrophy

• Grant number: 20/12112-1
• Support Opportunities: Scholarships in Brazil - Doctorate
• Start date: May 01, 2021
• End date: May 31, 2025
• Field of knowledge: Health Sciences - Medicine - Medical Clinics
• Principal Investigator: Licio Augusto Velloso
• Grantee: Maria Eduarda Martelli
• Host Institution: Faculdade de Ciências Médicas (FCM). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
• Associated research grant: 13/07607-8 - OCRC - Obesity and Comorbidities Research Center, AP.CEPID
• Associated scholarship(s): 24/10432-0 - Exploring the brown adipose tissue in Congenital Generalized Lipodystrophy and Familial Partial Lipodystrophy, BE.EP.DR

Abstract

Inherited lipodystrophies can present in generalized and partial forms, and they share the common feature of dysfunctional white adipose tissue (WAT), with a greater extent of fat loss being associated with more severe metabolic complications. Brown adipose tissue (BAT) has a different embryonic origin than WAT, and the presence and functionality of BAT in lipodystrophies are unknown. Objective: To determine whether BAT is present and functional in congenital generalized lipodystrophy (CGL) and familial partial lipodystrophy (FPL).Methodology: This is a multicenter cross-sectional study to be conducted with a non-probabilistic sample of 31 individuals with a confirmed molecular diagnosis of CGL (n=18) and FPL (n=13). The following data will be collected from medical records: personal history of relevant diseases (diabetes, hypertension, dyslipidemia, hepatic steatosis, pancreatitis, cardiovascular diseases), chronic medications (oral antidiabetics, insulin, antihypertensives, statins, fibrates, and leptin), and the most recent biochemical data (glucose, glycated hemoglobin, insulin, HOMA-IR, AST, ALT, total cholesterol and fractions, triglycerides, C-reactive protein, and creatinine). Anthropometric assessments (weight, height, and waist, hip, and neck circumferences) will be conducted. Dual-energy X-ray absorptiometry (DXA) will be used to assess body composition. BAT will be evaluated using the gold standard method of 18F-fluorodeoxyglucose positron emission tomography combined with computed tomography (18F-FDG PET/CT), after two hours of cold exposure in a room acclimated to 18°C, following BARCIST recommendations. Carimas 2.10 software (Turku, Finland) will be used for image analysis. Regions of interest (ROIs) will be drawn in the supraclavicular and cervical areas-main BAT depots in adults. A mean standardized uptake value (SUVmean) ¿1.5 g/ml within the range of -190 to -10 HU will be considered as indicative of BAT presence.BAT activity data from eutrophic, obese (age- and sex-matched), and diabetic volunteers from previous studies will be used as controls. Perspectives: The study aims to determine whether patients with CGL and FPL have active BAT and whether the presence of this tissue is associated with the metabolic complications observed. The clinical relevance lies in the potential to offer a new therapeutic target for managing this disease if BAT activation is observed alongside improvements in existing clinical complications.