| Outcome Measures: |
Primary: Plasma NEFA appearance rate, NEFA appearance will be measured using i.v. administration of \[7,7,8,8-2H\]-palmitate (in 25% human albumin) from time -60 to +360 min, as slightly modified from previous descriptions, using Steele's non steady-state equations. Blood samples to measure plasma palmitate, oleate, linoleate, and total NEFA levels, \[7,7,8,8-2H\]-palmitate enrichments by GC/MS-MS., 2 years|Cardiac and hepatic uptake, will be determined using 11C-palmitate PET/CT. 180 MBq will be administered by bolus injection at postprandial time 90min. After a transmission scan and regional CT (40mA), a 30-min dynamic list-mode PET acquisition will be performed starting at time 90 min on a 18 cm-high thoraco-abdominal segment to include the left cardiac ventricle and most of the liver on a Philips Gemini TOF PET/CT, 2 years|WAT spillover NEFA appearance rates, WAT spillover NEFA will be determined from oral administration of \[U-13C\]-palmitate. Blood samples to measure plasma \[U-13C\]-palmitate and chylomicron-TG \[U-13C\]-palmitate enrichment by GC/MS-MS, 2 years|oxidative metabolism of NEFA, will be assessed by using 13C-palmitate, 2 years|cardiac and hepatic DFA uptake, will be assessed using PET/CT method with oral administration of 18FTHA, 2 years|whole-body organ-specific DFA partitioning, will be determined by whole-body CT (16 mA) followed by PET acquisition of 18FTHA, 2 years | Secondary: Insulin sensitivity, will be determined using the HOMA-IR (based on fasting insulin and glucose levels), 2 years|Insulin secretion rate, will be assessed using deconvolution of plasma C-peptide with standard C-peptide kinetic parameters, 2 years|β-cell function, will be assessed by calculation of the disposition index (DI) that is insulin secretion in response to the ambient insulin, 2 years|WAT size, by biopsy fixed in formalin, 2 years|hormonal response, will be determined using a multiplex assay system, 2 years|Lipoprotein lipase activity, will be assessed as on frozen 150-mg portions from biopsy, 2 years
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