Tomato Powder Inhibits Hepatic Steatosis and Inflammation Potentially Through Restoring SIRT1 Activity and Adiponectin Function Independent of Carotenoid Cleavage Enzymes in Mice

Abstract

Dietary TP can inhibit NAFLD independent of carotenoid cleavage enzymes, potentially through increasing SIRT1 activity and adiponectin production and decreasing Clostridium abundance.

Indirubin, a small molecular deriving from connectivity map (CMAP) screening, ameliorates obesity-induced metabolic dysfunction by enhancing brown adipose thermogenesis and white adipose browning

“…In particular, adiponectin plays a key role in mediating the benefits of BAT transplantation in rodents, including improvements in wholebody energy expenditure and glucose homeostasis [9][10][11]. Besides, previous research also reveals that patients with obesity and NAFLD exhibited a reduced adiponectin transcription in adipose tissue and decreased adiponectin concentration in plasma [71]. In addition, other moleculars, such as FGF21 and BMP, have also been suggested as exercise mimetics [72][73][74].…”

Dietary Tomato Powder Inhibits High-Fat Diet–Promoted Hepatocellular Carcinoma with Alteration of Gut Microbiota in Mice Lacking Carotenoid Cleavage Enzymes

“…This study was approved by the Institutional Animal Care and Use Committee at the Jean Mayer USDA Human Nutrition Research Center on Aging (JM-HNRCA) at Tufts University. Male BCO1 À/À BCO2 À/À double KO mice were previously generated as described (27,28). Mice were bred in an Association for Assessment and Accreditation of Laboratory Animal Care-accredited animal facility at the JM-HNRCA at Tufts University.…”

“…with 10 mL DEN/g body weight or sham saline at 2 weeks of age. At 6 weeks of age, mice were fed an HFD as a promoter for hepatic tumorigenesis with or without dietary TP intervention for 24 weeks: High fat diet [DENþHFD group, n ¼ 9, semipurified diet F3282, 60% calories from fat (C18:2 linoleic fatty acid, 36.6 gm/kg; C18:3 linolenic fatty acid, 3.6 gm/kg; total Saturated fatty acid, 141 gm/kg; total monounsaturated fatty acid, 162 gm/kg; total polyunsaturated fatty acid, 40.2 gm/kg); BioServ] or HFD with TP (DENþHFDþTP group, n ¼ 9, TP, 41.9 g/kg diet, Kagome, Inc.), as described (27). The specific batch of TP used in this study contained 2.39 mg of lycopene, 0.11 mg of b-carotene, 0.29 mg of ascorbic acid, and 0.32 mg of a-tocopherol per gram of TP, analyzed by high-performance liquid chromatography (HPLC).…”

“…We did not determine all other nutrients for this specific batch of TP. The dose of TP was referred to the lycopene supplementation, which was found to inhibit HFDinduced fatty liver disease in our previous study (27) which indicated that the lycopene-supplemented dose of 100 mg/kg diet is equivalent to approximately 8.1 mg lycopene/day in a 60 kg adult man. According to the USDA food composition database (USDA, 2012, Available from: http://ndb.nal.usda.gov/ndb/search/list), the average amount of lycopene is around 2.57 mg per 100 g in red tomato or 15 mg per 100 g in tomato sauce.…”

“…Indeed, we observed that BCO1 À/À /BCO2 À/À double knockout (KO) mice developed liver steatosis and had significantly higher levels of triglyceride in the liver and plasma compared with wild-type animals (26). Very recently, we found that dietary tomato powder (TP) feeding inhibited NAFLD in the BCO1 À/À /BCO2 À/À double KO mice by upregulating sirtuin 1 (SIRT1) activity and AMP-activated protein kinase (AMPK) phosphorylation, decreasing lipogenesis and hepatic fatty acid uptake, and increasing fatty acid b-oxidation (27). However, (1) whether the whole tomato feeding can inhibit HFD-promoted inflammation and HCC development is unclear; (2) the importance of BCO1 and BCO2 in biological activities of the whole tomato against HCC development is unknown; and (3) the effects of the whole tomato feeding on gut microbiota in HFD-promoted hepatic tumorigenesis has not been explored.…”