Lycopene prevents non-alcoholic fatty liver disease through regulating hepatic NF-κB/NLRP3 inflammasome pathway and intestinal microbiota in mice fed with high-fat and high-fructose diet

Abstract

Lycopene (LY) belongs to carotenoids and is abundant in red fruits and vegetables. Several previous studies suggested that LY is beneficial for ameliorating non-alcoholic fatty liver disease (NAFLD), while the potential mechanisms are unclear. The present study aimed to clarify the potential mechanisms of LY in preventing NAFLD via exploring the hepatic NF-κB/NLRP3 inflammasome pathway and intestinal microbiota composition in high-fat and high-fructose diet (HFFD)-fed mice. Fifty eight-week-old male C57BL/6J mice were randomly assigned into 5 groups: Normal control group (NC); HFFD group; HFFD with low dose of lycopene group (LLY, 20 mg/kg/d); HFFD with high dose of lycopene group (HLY, 60 mg/kg/d) and HFFD with resveratrol group (RSV, 50 mg/kg/d, positive control). After 8 weeks, feces were collected and the 12 h fasted mice were sacrificed to acquire tissues and blood for parameters measurement. The results showed that the mice in LLY, HLY and RSV groups had significantly lower body weight gain, weight of white adipose tissue, serum levels of high density lipoprotein-cholesterol (HDL-C), low density lipoprotein-cholesterol (LDL-C), lipopolysaccharide (LPS), alanine aminotransferase (ALT), and hepatic concentrations of triglyceride (TG) and interleukin-6 (IL-6) than that in the HFFD group (p < 0.05). HLY and RSV groups also displayed lower serum levels of TG, total cholesterol (TC) and hepatic levels of tumor necrosis factor-α (TNF-α) than the HFFD group (p < 0.05). Liver protein expressions of NLRP3, Pro-Caspase-1, Caspase-1 and NF-κB were lower in the LLY, HLY and RSV groups than those in the HFFD group (p < 0.05). The feces of LY -treated mice had higher relative levels of SCFAs producing bacteria Allobaculum and lower destructive bacteria, including Firmicutes, Lachnospiraceae_NK4A136_group, Desulfovibrio, and Alistipes over the HFFD group (p < 0.05). RSV group also displayed lower fecal levels of Lachnospiraceae_NK4A136_group, Desulfovibrio, and Alistipes than the HFFD group (p < 0.05). In conclusion, LY might prevent NAFLD by suppressing hepatic NF-κB/NLRP3 inflammasome pathway and attenuating gut microbiota dysbiosis.

The Importance of Antioxidant Activity for the Health-Promoting Effect of Lycopene

“…Lycopene affected the inflammatory signaling pathway associated with hepatic NLRP3 by reducing the expression of the liver proteins Pro-Caspase-1, Caspase-1, NLRP3, and NF-κB. The study showed that lycopene may prevent NAFLD by inhibiting the NF-κB/NLRP3 inflammasome pathway in the liver [110]. In another study, lycopene, luteolin, and their combination were shown to activate the adenosine monophosphate-activated protein kinase (AMPK) pathway.…”

“…It also increased the total antioxidant capacity (TAP) as well as SOD and CAT activity in the liver [109]. Gao et al [110] studied the effect of lycopene on the hepatic NF-κB/NLRP3 inflammasome pathway in C57BL/6J mice with NAFLD. The tested carotenoid reduced body weight gain and reduced white adipose tissue mass in mice.…”

Recent Advances in the Therapeutic Potential of Carotenoids in Preventing and Managing Metabolic Disorders

“…In the case of disorders that arise from cognitive decline, such as dementia, α - and β -carotene, lutein, and zeaxanthin have been associated with improved cognitive functionality [ 113 ]. On the other hand, treatment with lycopene has been demonstrated to prevent the development of NAFLD in C57BL/6J mice by suppressing the hepatic NFκ-B/NLRP3 inflammasome pathway [ 114 ]. In contrast, treatment with zeaxanthin has been shown to decrease the generation of ROS, inhibit ferroptosis, enhance mitochondrial dysfunction, and diminish lipid peroxidation in free fatty acid-induced HepG2 cells.…”

Review of microbiota gut brain axis and innate immunity in inflammatory and infective diseases

“…Other studies have showed that various stimuli caused by neuroinflammatory or degenerative processes can promote the activation of NLRP3 inflammasome, thereby altering the gut microbiota ( Pellegrini et al., 2017 ). It was found that the knockout of NLRP3 could lead to the increase of Firmicutes and a decrease in Bacteroidetes in the gut of mice, as well as the increase of Lachnospiraceae , Ruminococcaceae and Prevotellaceae ( Gao et al., 2023 ). Collectively, inflammasome may be the key target for directly regulating inflammation and infectious diseases.…”