Selective Depletion of Hepatic Kupffer Cells Significantly Alleviated Hepatosteatosis and Intrahepatic Inflammation Induced by High Fat Diet

Abstract

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). 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. 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). Selective depletion of hepatic Kupffer cells significantly alleviated hepatosteatosis and intrahepatic inflammation induced by HFD.