Super paramagnetic iron oxide MRI shows defective Kupffer cell uptake function in non-alcoholic fatty liver disease.
BACKGROUND
The pathogenesis of non-alcoholic fatty liver disease (NAFLD) is incompletely understood. Kupffer cells (KCs), phagocytic liver-resident macrophages, provide a protective barrier against egress of endotoxin from the portal to the systemic circulation. It is not known if KC phagocytic function is impaired in NAFLD. Super-paramagnetic iron oxide (SPIO) magnetic resonance imaging is a comparative technology dependent on KC phagocytic function.


OBJECTIVE
To evaluate KC uptake function, in patients and experimental animals with NAFLD, using SPIO.


METHODS
Abdominal CT and histological examination of liver biopsy specimens were used to estimate the degree of steatosis in patients with NAFLD and controls with chronic hepatitis C. SPIO-MRI was then performed in all patients. Normal rats fed a methionine-choline-deficient diet to induce non-alcoholic steatohepatitis (NASH), the more severe stage of NAFLD, and obese, insulin resistant, Zucker fa/fa rats with steatohepatitis, were also studied with SPIO-MRI and analysed for hepatic uptake of fluorescent microbeads. Immunohistochemical analysis evaluated the numbers of KCs in patients and rat livers.


RESULTS
Relative signal enhancement (RSE), inversely proportional to KC function, was higher in patients with NAFLD than in controls and with the degree of steatosis on CT. RSE also positively correlated with the degree of steatosis on histology and was similarly higher in rats with induced severe NAFLD (NASH). On immunohistochemistry, defective phagocytic function was the result of reduced phagocytic uptake and not due to reduced KC numbers in rats or patients with NAFLD.


CONCLUSIONS
KC uptake function is significantly impaired in patients with NAFLD and experimental animals with NASH, worsens with the degree of steatosis and is not due to a reduction of KC numbers.
Asanuma
Taketoshi
T
Department of Radiology, Graduate School of Veterinary Medicine, Hokkaido University, Sapporo, Hokkaido, Japan.
Ono
Masafumi
M
Kubota
Kei
K
Hirose
Akira
A
Hayashi
Yoshihiro
Y
Saibara
Toshiji
T
Inanami
Osamu
O
Ogawa
Yasuhiro
Y
Enzan
Hideaki
H
Onishi
Saburo
S
Kuwabara
Mikinori
M
Oben
Jude A
JA
D000818:Animals; D002452:Cell Count; D003287:Contrast Media; D003911:Dextrans; D004195:Disease Models, Animal; D005234:Fatty Liver / Q000473:pathology* / Q000503:physiopathology; D005260:Female; D052203:Ferrosoferric Oxide; D006801:Humans; D007728:Kupffer Cells / Q000502:physiology*; D008102:Liver Circulation / Q000502:physiology; D008279:Magnetic Resonance Imaging / Q000379:methods; D058185:Magnetite Nanoparticles; D008297:Male; D008833:Microcirculation / Q000502:physiology; D010587:Phagocytosis / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D011924:Rats, Zucker; D012720:Severity of Illness Index
D003287:Contrast Media; D003911:Dextrans; D058185:Magnetite Nanoparticles; C065507:ferumoxides; D052203:Ferrosoferric Oxide