Blackcurrant (Ribes nigrum) Consumption Prevents Non‐alcoholic Steatohepatitis in C57BL/6J Mice with Diet‐induced Obesity
Authors: Lee Yoojin , Pham Tho X. , Bae Minkyung , Hu Siqi , O'Neill Edward , Han Catherine , Caceres Christian , Park Young‐Ki , Lee Ji‐Young 
Published: November 2023

Non‐alcoholic steatohepatitis (NASH) is characterized by excessive fat accumulation and inflammation in the liver. NASH further progresses to cirrhosis and hepatocellular carcinoma. With increased prevalence of NASH particularly in obese population, preventative/therapeutic strategies for NASH are needed. To investigate whether consumption of whole blackcurrant (Ribes nigrum) can prevent the development of obesity‐induced NASH, male C57BL/6J mice at age of 7 weeks were fed one of the following 4 diets for 24 weeks: a low fat control (LF; 13 % energy from fat); a LF with blackcurrant (LF‐BC; 6% of freeze‐dried whole blackcurrant powder by weight); an obesogenic high fat/high sucrose control (HF/HS; 57%/28% energy from fat/sucrose); and a HF/HS containing 6% blackcurrant powder (HF/HS‐BC). HF/HS markedly increased body weights of mice, and blackcurrant did not alter body weights both in lean and obese mice. Hepatic triglyceride levels of HF/HS‐BC group were significantly lower than HF/HS control although liver weights were not significantly different. Hepatic mRNA abundance of F4/80, a macrophage marker, was significantly increased by HF/HS, which was attenuated by blackcurrant to the similar level of LF groups. M1 macrophage markers, e.g., CD11c and monocyte chemoattractant protein 1 (MCP‐1), and fibrogenic genes, e.g., transforming growth factor β1 and collagen type I alpha 1, were significantly higher in HF/HS group than HF/HS‐BC group. Furthermore, blackcurrant significantly decreased the expression of CD206, a M2 macrophage marker, MCP‐1, and toll‐like receptor 4 in obese mice. The gene analysis demonstrated that blackcurrant attenuated obesity‐induced expression of pro‐inflammatory and pro‐fibrogenic genes. Using serum miRNA array, we found that HF/HS significantly increased serum levels of miR‐122‐5p and miR‐192‐5p, known serum markers of NAFLD, compared with LF control. However, the levels were significantly lower in mice fed the HF/HS‐BC diet. Additionally, plasma alanine aminotransferase concentrations were significantly decreased by blackcurrant consumption in both lean and obese mice at 16 and 24 weeks on the experimental diets, supporting the protective role of blackcurrant in the development of NASH. To gain insight into the anti‐inflammatory effect of blackcurrant, flow cytometric analysis was conducted for the determination of monocyte phenotypes in the spleen and bone marrow. There were no significant differences in Ly6C− to Ly6C+ ratios and total numbers of bone marrow monocytes. However, in the spleen, HF/HS diet significantly decreased the ratios of Ly6C− to Ly6C+ monocytes while significantly increasing the number of total splenic monocytes compared with LF control. The increased number of total splenic monocytes by HF/HS was significantly attenuated by blackcurrant. Taken together, our data indicate that whole blackcurrant exerts anti‐inflammatory and anti‐fibrotic actions in obese mice with NASH, at least in part, by preventing an increase in splenic monocyte population induced by obesity. Therefore, blackcurrant consumption may be beneficial for the prevention of NASH in obese population.Support or Funding InformationUSDA AFRI 2016‐67017‐24463