Selective depletion of hepatic Kupffer cells significantly alleviated hepatosteatosis and intrahepatic inflammation induced by high fat diet.
OBJECTIVE
To address the impact of Kupffer cell ablation via intraperitoneal injection of gadolinium chloride (GdCl3) on hepatosteatosis, intrahepatic inflammation and other metabolic derangements induced by high-fat diet (HFD).


METHODS
C57/BCL male mice were fed with either standard normal diet or HFD. Meanwhile, mice received an intraperitoneal injection of either natural saline (5mL/kg) or 0.2% GdCl3 solution (10mg/kg) twice a week. After 8 weeks, intraperitoneal glucose tolerance test (IPGTT) was performed. F4/80 expression was quantified by immunohistochemistry, immunofluorescence and quantitative (q) RT-PCR. Adipokines in liver were detected via qRT-PCR.


RESULTS
HFD led to clear Kupffer cell infiltration and migration into areas surrounding the hepatic central vein. Both F4/80 expression and F4/80-positive cells in the liver were significantly reduced after GdCl3 administration (both p<0.01). Liver triglyceride and cholesterol deposition decreased dramatically after GdCl3 administration (p<0.01, p<0.05, respectively). TNF-a and IL-6 expression in mouse liver decreased significantly after Kupffer cell depletion (both p<0.01). Daily diet amount, weight and the area under IPGTT curve of the mice fed with HFD were clearly decreased after Kupffer cell depletion, though not statistically significant (all p>0.05).


CONCLUSIONS
Selective depletion of hepatic Kupffer cells significantly alleviated hepatosteatosis and intrahepatic inflammation induced by HFD.
Department of Endocrinology and Metabolism, Fundan University, Shanghai, China.
Lili
L
Chen
Hongying
H
Ye
Xiaolong
X
Zhao
Qing
Q
Miao
Yiming
Y
Li
Renming
R
Hu
D000818:Animals; D000943:Antigens, Differentiation / Q000032:analysis; D001786:Blood Glucose / Q000032:analysis; D059305:Diet, High-Fat; D005234:Fatty Liver / Q000517:prevention & control*; D005682:Gadolinium / Q000633:toxicity; D007249:Inflammation / Q000517:prevention & control*; D007333:Insulin Resistance; D015850:Interleukin-6 / Q000235:genetics; D007728:Kupffer Cells / Q000502:physiology*; D008099:Liver / Q000378:metabolism / Q000473:pathology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics
D000943:Antigens, Differentiation; D001786:Blood Glucose; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; C036763:monocyte-macrophage differentiation antigen; D005682:Gadolinium; C038958:gadolinium chloride