Fatty acid metabolism in the liver, measured by positron emission tomography, is increased in obese individuals.
OBJECTIVE
Hepatic lipotoxicity results from and contributes to obesity-related disorders. It is a challenge to study human metabolism of fatty acids (FAs) in the liver. We combined (11)C-palmitate imaging by positron emission tomography (PET) with compartmental modeling to determine rates of hepatic FA uptake, oxidation, and storage, as well as triglyceride release in pigs and human beings.


METHODS
Anesthetized pigs underwent (11)C-palmitate PET imaging during fasting (n = 3) or euglycemic hyperinsulinemia (n = 3). Metabolic products of FAs were measured in arterial, portal, and hepatic venous blood. The imaging methodology then was tested in 15 human subjects (8 obese subjects); plasma (11)C-palmitate kinetic analyses were used to quantify systemic and visceral lipolysis.


RESULTS
In pigs, PET-derived and corresponding measured FA fluxes (FA uptake, esterification, and triglyceride FA release) did not differ and were correlated with each other. In human beings, obese subjects had increased hepatic FA oxidation compared with controls (mean +/- standard error of the mean, 0.16 +/- 0.01 vs 0.08 +/- 0.01 micromol/min/mL; P = .0007); FA uptake and esterification rates did not differ between obese subjects and controls. Liver FA oxidation correlated with plasma insulin levels (r = 0.61, P = .016), adipose tissue (r = 0.58, P = .024), and systemic insulin resistance (r = 0.62, P = .015). Hepatic FA esterification correlated with the systemic release of FA into plasma (r = 0.71, P = .003).


CONCLUSIONS
PET imaging can be used to measure FA metabolism in the liver. By using this technology, we found that obese individuals have increased hepatic oxidation of FA, in the context of adipose tissue insulin resistance, and increased FA flux from visceral fat. FA flux from visceral fat is proportional with the mass of the corresponding depot.
Iozzo
Patricia
P
Turku PET Centre, and Department of Medicine, University of Turku, Turku, Finland. patricia.iozzo@ifc.cnr.it
Bucci
Marco
M
Roivainen
Anne
A
Någren
Kjell
K
Järvisalo
Mikko J
MJ
Kiss
Jan
J
Guiducci
Letizia
L
Fielding
Barbara
B
Naum
Alexandru G
AG
Borra
Ronald
R
Virtanen
Kirsi
K
Savunen
Timo
T
Salvadori
Piero A
PA
Ferrannini
Ele
E
Knuuti
Juhani
J
Nuutila
Pirjo
P
D000818:Animals; D002250:Carbon Radioisotopes; D016022:Case-Control Studies; D004195:Disease Models, Animal; D005215:Fasting / Q000097:blood; D005227:Fatty Acids / Q000097:blood*; D006801:Humans; D006946:Hyperinsulinism / Q000097:blood / Q000000981:diagnostic imaging; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance; D050152:Intra-Abdominal Fat / Q000378:metabolism* / Q000473:pathology; D008066:Lipolysis; D008099:Liver / Q000098:blood supply / Q000000981:diagnostic imaging* / Q000378:metabolism; D008279:Magnetic Resonance Imaging; D008875:Middle Aged; D009765:Obesity / Q000097:blood / Q000000981:diagnostic imaging* / Q000473:pathology; D010084:Oxidation-Reduction; D019308:Palmitic Acid; D049268:Positron-Emission Tomography; D011446:Prospective Studies; D019275:Radiopharmaceuticals; D013552:Swine; D014280:Triglycerides / Q000097:blood; D015854:Up-Regulation
D002250:Carbon Radioisotopes; D005227:Fatty Acids; D007328:Insulin; D019275:Radiopharmaceuticals; D014280:Triglycerides; D019308:Palmitic Acid