Gathaiya, Nicola

ObjectiveThis study tested whether substrate concentrations or fatty acid storage proteins predict storage of endogenous lipids in visceral adipose tissue (VAT) and upper body subcutaneous adipose tissue (UBSQ) fat.MethodsThe day prior to surgery, 25 patients undergoing bariatric procedures received an infusion of autologous [1‐14C]triolein‐labeled very low‐density lipoprotein (VLDL) particles, and during surgery, they received a continuous [U‐13C]palmitate infusion/bolus [9,10‐3H]palmitate tracer. VAT and UBSQ fat were collected to measure VLDL‐triglyceride (TG) storage, direct free fatty acid (FFA) storage rates, CD36 content, lipoprotein lipase (LPL), acyl‐CoA synthetase, diacylglycerol acetyl‐transferase, and glycerol‐3‐phosphate acyltransferase activities.ResultsStorage of VLDL‐TG and FFA‐palmitate in UBSQ and VAT was not different. Plasma palmitate concentrations correlated with palmitate storage rates in UBSQ and VAT (r = 0.46, P = 0.02 and r = 0.46, P = 0.02, respectively). In VAT, VLDL‐TG storage was correlated with VLDL concentrations (r = 0.53, P < 0.009) and LPL (r = 0.42, P < 0.05). In UBSQ, VLDL‐TG storage was correlated with LPL (r = 0.42, P < 0.05). CD36, acyl‐CoA synthetase, glycerol‐3‐phosphate acyltransferase, and diacylglycerol acetyl‐transferase were not correlated with VLDL‐TG or palmitate storage.ConclusionsAdipose storage of VLDL‐TG is predicted by VLDL‐TG concentrations and LPL; FFA concentrations predict direct adipose tissue FFA storage rates.

AbstractObjectiveNonalcoholic fatty liver disease can lead to hepatic inflammation/damage. Understanding the physiological mechanisms that contribute to excess hepatic lipid accumulation may help identify effective treatments.DesignWe recruited 25 nondiabetic patients with severe obesity scheduled for bariatric surgery. To evaluate liver export of triglyceride fatty acids, we measured very-low-density lipoprotein (VLDL)–triglyceride secretion rates the day prior to surgery using an infusion of autologous [1-14C]triolein-labeled VLDL particles. Ketone body response to fasting and intrahepatic long-chain acylcarnitine concentrations were used as indices of hepatic fatty acid oxidation. We measured intraoperative hepatic uptake rates of plasma free fatty acids using a continuous infusion of [U-13C]palmitate, combined with a bolus dose of [9,10-3H]palmitate and carefully timed liver biopsies. Total intrahepatic lipids were measured in liver biopsy samples to determine fatty liver status. The hepatic concentrations and enrichment from [U-13C]palmitate in diacylglycerols, sphingolipids, and acyl-carnitines were measured using liquid chromatography/tandem mass spectrometry.ResultsAmong study participants with fatty liver disease, intrahepatic lipid was negatively correlated with VLDL-triglyceride secretion rates (r = −0.92, P = 0.01) but unrelated to hepatic free fatty acid uptake or indices of hepatic fatty acid oxidation. VLDL-triglyceride secretion rates were positively correlated with hepatic concentrations of saturated diacylglycerol (r = 0.46, P = 0.02) and sphingosine-1-phosphate (r = 0.44, P = 0.03).ConclusionWe conclude that in nondiabetic humans with severe obesity, excess intrahepatic lipid is associated with limited export of triglyceride in VLDL particles rather than increased uptake of systemic free fatty acids.

Positron emission tomography (PET) radiopharmaceuticals can noninvasively measure free fatty acid (FFA) uptake into adipose tissue. We studied 29 volunteers to test whether abdominal and femoral subcutaneous adipose tissue FFA uptake measured using [1- 11 C]palmitate PET agrees with FFA storage rates measured using an intravenous bolus of [1- 14 C]palmitate and adipose biopsies. The dynamic left ventricular cavity PET images combined with blood sample radioactivity corrected for the 11 CO 2 content were used to create the blood time activity curve (TAC), and the constant ( K i ) was determined using Patlak analysis of the TACs generated for regions of interest in abdominal subcutaneous fat. These data were used to calculate palmitate uptake rates in abdominal subcutaneous adipose tissue (µmol·kg −1 ·min −1 ). Immediately after the dynamic imaging, a static image of the thigh was taken to measure the standardized uptake value (SUV) in thigh adipose tissue, which was scaled to each participant’s abdominal adipose tissue SUV to calculate thigh adipose palmitate uptake rates. Abdominal adipose palmitate uptake using PET [1- 11 C]palmitate was correlated with, but significantly ( P < 0.001) greater than, FFA storage measured using [1- 14 C]palmitate and adipose biopsy. Thigh adipose palmitate measured using PET calculation was positively correlated ( R 2 = 0.44, P < 0.0001) with and not different from the biopsy approach. The relative differences between PET measured abdominal subcutaneous adipose tissue palmitate uptake and biopsy-measured palmitate storage were positively correlated ( P = 0.03) with abdominal subcutaneous fat. We conclude that abdominal adipose tissue FFA uptake measured using PET does not equate to adipose FFA storage measured using biopsy techniques.

PET radiopharmaceuticals can noninvasively measure free fatty acid (FFA) tissue uptake. Investigators often use PET scan-derived data to calculate FFA flux. We tested whether the [1-11C]palmitate PET measures of palmitate flux provide results equivalent to a continuous infusion of [U-13C]palmitate. Nine volunteers participated in study 1 to evaluate whether a rapidly (10–20 s) given bolus of [1-11C]palmitate affects calculated flux results. Thirty volunteers participated in study 2, which was identical to study 1 except that the [1-11C]palmitate bolus was given over 1 min. Volunteers in both studies also received a continuous intravenous infusion of [U-13C]palmitate. Plasma palmitate concentrations and enrichment were measured by liquid chromatography-mass spectrometry. The PET/CT images were analyzed on a workstation running PMOD. Palmitate flux was estimated using PET time-activity curve (TAC) data from regions of interest in the left ventricle (LV) and aorta both with and without hybrid TACs that employed the11CO2-corrected data for the first 5 min and the11CO2-corrected blood radioactivity for the remainder of the PET scan. Palmitate flux in study 1 measured with PET [1-11C]palmitate and [U-13C]palmitate were not correlated, and the PET [1-11C]palmitate flux was significantly less than the [U-13C]palmitate measured flux. In study 2, the palmitate flux using PET [1-11C]palmitate hybrid LV models provided closer mean estimates of [U-13C]palmitate measured flux. The best PET calculation approaches predicted 64% of the interindividual variance in [U-13C]palmitate measured flux. Palmitate kinetics measured using [1-11C]palmitate/PET do not provide the same palmitate kinetic results as the continuous infusion [U-13C]palmitate approach.