Non-alcoholic fatty liver disease and non-alcoholic steatohepatitis are characterized by an increase in hepatic triglyceride content with infiltration of immune cells, which can cause steatohepatitis and hepatic insulin resistance. C-C chemokine receptor 7 (CCR7) is primarily expressed in immune cells, and CCR7 deficiency leads to the development of multi-organ autoimmunity, chronic renal disease and autoimmune diabetes. Here, we investigated the effect of CCR7 on hepatic steatosis in a mouse model and its underlying mechanism. Our results demonstrated that body and liver weights were higher in the CCR7 '/' mice than in the wild-type (WT) mice when they were fed a high-fat diet. Further, glucose tolerance and insulin sensitivity were markedly diminished in CCR7 '/' mice. The number of invariant natural killer T (iNKT) cells was reduced in the livers of the CCR7 '/' mice. Moreover, liver inflammation was detected in obese CCR7 '/' mice, which was ameliorated by the adoptive transfer of hepatic mononuclear cells from WT mice, but not through the transfer of hepatic mononuclear cells from CD1d '/' or interleukin-10-deficient (IL-10 '/') mice. Overall, these results suggest that CCR7 + mononuclear cells in the liver could regulate obesity-induced hepatic steatosis via induction of IL-10-expressing iNKT cells.
Bibliographical noteFunding Information:
We thank Dr Martin Lipp from Max Delbruck Center for Molecular Medicine for CCR7−/− mice. This research was supported by the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Science, ICT and Future Planning (NRF-2017R1A2B2001963, NRF-2016R1A4A1010115 and NRF-2016R1A6A3A11932829). This study was also supported by a grant from the Korean Health Technology R&D Project, Ministry of Health & Welfare, Republic of Korea (HI15C0450). This study was supported by 2015 Research Grant from Kangwon National University (No. 520150291).
All Science Journal Classification (ASJC) codes
- Medicine (miscellaneous)
- Endocrinology, Diabetes and Metabolism
- Nutrition and Dietetics