|LI, CHENG-CHUNG - Jean Mayer Human Nutrition Research Center On Aging At Tufts University|
|LIU, CHUN - Jean Mayer Human Nutrition Research Center On Aging At Tufts University|
|FU, MAOBIN - Kagome Co, Ltd|
|HU, KANG-QUAN - Jean Mayer Human Nutrition Research Center On Aging At Tufts University|
|AIZAWA, KOICHI - Kagome Co, Ltd|
|TAKAHASHI, SHINGO - Kagome Co, Ltd|
|HIROYUKI, SUGANUMA - Kagome Co, Ltd|
|CHENG, JUNRUI - Jean Mayer Human Nutrition Research Center On Aging At Tufts University|
|VON LINTIG, JOHANNES - Case Western Reserve University (CWRU)|
|WANG, XIANG-DONG - Jean Mayer Human Nutrition Research Center On Aging At Tufts University|
Submitted to: Molecular Nutrition and Food Research
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 12/11/2017
Publication Date: 1/8/2018
Citation: Li, C., Liu, C., Fu, M., Hu, K., Aizawa, K., Takahashi, S., Hiroyuki, S., Cheng, J., Von Lintig, J., Wang, X. 2018. Tomato powder inhibits hepatic steatosis and inflammation potentially through restoring SIRT1 activity and adiponectin function independent of carotenoid cleavage enzymes in mice. Molecular Nutrition and Food Research. 62(8):e1700738. https://doi.org/10.1002/mnfr.201700738.
Interpretive Summary: One of the consequences of the obesity epidemic is an increased prevalence of nonalcoholic fatty liver disease (NAFLD). We and others have previously demonstrated that lycopene, a pigment found in tomatoes and type of carotenoid, lessens the high fat diet-induced NAFLD development. Genetic variants of the lycopene metabolizing genes, BCO1/BCO2, are prevalent in humans and affect carotenoid status. However, the importance of BCO1/BCO2 in protective effects of tomato against NAFLD development and whether dietary whole tomato (tomato powder) would ameliorate the NAFLD in the absence of both BCO1 and BCO2 in mice remains unknown. The present study demonstrated that dietary tomato powder effectively inhibited high fat diet-induced NAFLD independent of carotenoid cleavage enzymes. Additionally, we observed that the tomato powder supplementation resulted in a lower relative abundance of the gram-positive bacteria (genus Clostridium) in gut, as compared with the high fat diet alone group. This study opened a new avenue to investigate whether the underlying mechanism of the protective effect of tomato powder as a whole food is due to influencing the gut microbiome.
Technical Abstract: Scope: Beta-carotene-15,15'-oxygenase (BCO1) and beta-carotene-9',10'-oxygenase (BCO2) metabolize lycopene to biologically active metabolites, which can ameliorate nonalcoholic fatty liver disease (NAFLD). We investigated the effects of tomato powder (TP), a whole food containing substantial lycopene, on NAFLD development and gut microbiome in the absence of both BCO1 and BCO2. Method and Results: BCO1-/-/BCO2-/- double knockout mice were fed a high fat diet (HFD) alone or with TP supplementation for 24 weeks. Pathology and molecular biomarkers were assessed in the liver and mesenteric adipose tissue (MAT). Multiplexed 16S rRNA gene sequencing was performed using DNA extracted from cecum fecal samples. TP supplementation reduced HFD-induced NAFLD in BCO1-/-/BCO2-/- mice. This was associated with increased SIRT1 activity, nicotinamide phosphoribosyltransferase expression and AMPK phosphorylation, and subsequently decreased lipogenesis, hepatic fatty acid uptake, and increasing fatty acid B-oxidation. TP feeding decreased mRNA expression of pro-inflammatory genes in liver and MAT, which were associated with increased MAT adiponectin expression, plasma adiponectin and hepatic adiponectin receptor-2. Additionally, TP feeding increased microbial richness and decreased relative abundance of the genus Clostridium (C. sp. ID4 and C. disporicum). Conclusion: Dietary TP can inhibit NAFLD independent of carotenoid cleavage enzymes, potentially through increasing SIRT1 activity and adiponectin production and decreasing Clostridium abundance.