Blackcurrant (Ribes nigrum) Prevents Obesity‐Induced Nonalcoholic Steatohepatitis in Mice

Abstract

Objective: With increasing prevalence of nonalcoholic steatohepatitis (NASH), effective strategies to prevent NASH are needed. This study investigated whether the consumption of blackcurrant (Ribes nigrum) can prevent the development of obesity-induced NASH in vivo. Methods: Male C57BL/6J mice were fed a low-fat control diet, a low-fat diet with 6% whole blackcurrant powder, an obesogenic high-fat/high-sucrose control diet (HF), or a high-fat/high-sucrose diet containing 6% whole blackcurrant powder (HF-B) for 24 weeks. Results: HF significantly increased, whereas HF-B markedly decreased, liver weights and triglyceride. Furthermore, blackcurrant attenuated obesity-induced infiltration of macrophages in the liver, in particular, the M1 type, and also suppressed the hepatic expression of fibrogenic genes and fibrosis. Flow cytometric analysis showed that HF significantly increased the percentages of monocytes of total splenocytes, which was markedly attenuated by blackcurrant. HF-B decreased lipopolysaccharide-stimulated mRNA expression of interleukin 1β and tumor necrosis factor α in splenocytes, compared with those from HF controls. Moreover, the levels of circulating and hepatic miR-122-5p and miR-192-5p, known markers for nonalcoholic fatty liver disease, were significantly increased by HF but decreased by HF-B. Conclusions: The study's findings indicate that blackcurrant consumption prevents obesity-induced steatosis, inflammation, and fibrosis in the liver.

Blackcurrant (Ribes nigrum) Extract Exerts an Anti-Inflammatory Action by Modulating Macrophage Phenotypes

“…In our previous study, we found blackcurrant consumption attenuated obesity-associated inflammation in the liver and LPS-stimulated inflammatory responses of splenocytes in HF diet-fed C57BL/6 mice [12]. As macrophages play a major role in inflammation, we determined whether blackcurrant exerts its anti-inflammatory actions via suppressing inflammatory responses in macrophages using polyphenol-rich BCE.…”

“…Increases in total macrophage numbers and the population of pro-inflammatory M1 macrophages in adipose tissue and the liver have been reported as a hallmark of obesity-associated chronic inflammation [9,10,11,12]. As LPS stimulated-inflammatory responses are closely related to M1 polarization [6], we determined whether the anti-inflammatory actions of BCE in macrophages could be attributable to its ability to suppress macrophage polarization to M1.…”

“…Seven-week-old male C57BL/6J mice (Jackson Laboratory, Bar Harbor, ME, USA) were randomly assigned into four groups: a low fat control (LF; 13% energy from fat, n = 7), a LF with blackcurrant (LF-BC; 6% of freeze-dried, whole blackcurrant powder by weight, n = 7), an obesogenic high fat/high sucrose control (HF; 57%/28% energy from fat/sucrose, n = 14), or a HF containing 6% blackcurrant powder (HF-BC, n = 15), as we previously described [12]. As C57BL/6J mice are prone to develop obesity [21], mice fed a LF or LF-BC were on the experimental diets for one week to avoid any compounding effects of obesity-induced pro-inflammatory mediators in the circulation.…”

“…In obesity-associated inflammation, M1 macrophages are predominant in the inflamed tissue, producing ROS, nitric oxide (NO), and pro-inflammatory cytokines [8], which aggravate inflammation and damage tissue. Specifically, studies have reported that M1 macrophages in the liver and adipose tissue are increased in obesity [9,10,11,12]. Therefore, it is beneficial to inhibit macrophage polarization into M1 or to shift macrophage phenotype toward anti-inflammatory and pro-resolving M2 macrophages to prevent obesity-associated inflammation [13].…”

“…Our previous studies demonstrated that polyphenol-rich blackcurrant extract (BCE) prevented inflammation in the liver and adipose tissue of diet-induced obesity (DIO) mice [19,20]. Furthermore, we have shown increases in the hepatic expression of M1 macrophage markers, which was significantly attenuated by blackcurrant in DIO mice [12]. In the present study, we further investigated whether blackcurrant can modulate macrophage phenotypes to exert its anti-inflammatory actions with a primary focus on the role of blackcurrant in the regulation of macrophage polarization in vitro, utilizing both mouse and human macrophages.…”