Gao Xiang, Zhao Xia, Liu Min, Zhao Huimin, Sun Yongye
Institute of Nutrition and Health, College of Public Health, Qingdao University, Qingdao, China.
College of Life Sciences, Qingdao University, Qingdao, China.
Front Nutr. 2023 Mar 23;10:1120254. doi: 10.3389/fnut.2023.1120254. eCollection 2023.
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 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 ( < 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 ( < 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 ( < 0.05). The feces of LY -treated mice had higher relative levels of SCFAs producing bacteria and lower destructive bacteria, including , , , and over the HFFD group ( < 0.05). RSV group also displayed lower fecal levels of , , and than the HFFD group ( < 0.05). In conclusion, LY might prevent NAFLD by suppressing hepatic NF-κB/NLRP3 inflammasome pathway and attenuating gut microbiota dysbiosis.
番茄红素（LY）属于类胡萝卜素，在红色水果和蔬菜中含量丰富。先前的几项研究表明，LY有助于改善非酒精性脂肪性肝病（NAFLD），但其潜在机制尚不清楚。本研究旨在通过探究高脂高果糖饮食（HFFD）喂养小鼠的肝脏NF-κB/NLRP3炎性小体途径和肠道微生物群组成，阐明LY预防NAFLD的潜在机制。将58只8周龄雄性C57BL/6J小鼠随机分为5组：正常对照组（NC）；HFFD组；低剂量番茄红素HFFD组（LLY，20毫克/千克/天）；高剂量番茄红素HFFD组（HLY，60毫克/千克/天）和白藜芦醇HFFD组（RSV，50毫克/千克/天，阳性对照）。8周后，收集粪便，并对禁食12小时的小鼠进行处死，以获取组织和血液用于参数测量。结果显示，LLY、HLY和RSV组小鼠的体重增加、白色脂肪组织重量、血清高密度脂蛋白胆固醇（HDL-C）、低密度脂蛋白胆固醇（LDL-C）、脂多糖（LPS）、丙氨酸转氨酶（ALT）水平以及肝脏甘油三酯（TG）和白细胞介素-6（IL-6）浓度均显著低于HFFD组（<0.05）。HLY和RSV组的血清TG、总胆固醇（TC）水平以及肝脏肿瘤坏死因子-α（TNF-α）水平也低于HFFD组（<0.05）。LLY、HLY和RSV组肝脏中NLRP3、前半胱天冬酶-1、半胱天冬酶-1和NF-κB的蛋白表达低于HFFD组（<0.05）。与HFFD组相比，LY处理小鼠的粪便中产生短链脂肪酸的细菌相对水平较高，而包括[具体细菌名称缺失]、[具体细菌名称缺失]、[具体细菌名称缺失]和[具体细菌名称缺失]在内的有害细菌水平较低（<0.05）。RSV组粪便中[具体细菌名称缺失]、[具体细菌名称缺失]和[具体细菌名称缺失]的水平也低于HFFD组（<0.05）。总之，LY可能通过抑制肝脏NF-κB/NLRP3炎性小体途径和减轻肠道微生物群失调来预防NAFLD。
