BACKGROUND/AIMS: 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). METHODOLOGY: 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.
BACKGROUND/AIMS: 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). METHODOLOGY: 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.
Authors: Detlef Schuppan; Henning Grønbæk; Konstantin Kazankov; Simon Mark Dahl Jørgensen; Karen Louise Thomsen; Holger Jon Møller; Hendrik Vilstrup; Jacob George Journal: Nat Rev Gastroenterol Hepatol Date: 2019-03 Impact factor: 46.802