Genetic dissection in a mouse model reveals interactions between carotenoids and lipid metabolism

Palczewski, Grzegorz; Widjaja‐Adhi, Made Airanthi K.; Amengual, Jaume; Golczak, Marcin; Lintig, Johannes von

doi:10.1194/jlr.m069021

Cited by 35 publications

(24 citation statements)

References 50 publications

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“…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.…”

Section: Methodsmentioning

confidence: 99%

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

Xia

et al. 2018

Cancer Prevention Research

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Both incidence and death rate due to liver cancer have increased in the United States. Higher consumption of lycopene-rich tomato and tomato products is associated with a decreased risk of cancers. b-Carotene-15, 15 0 -oxygenase (BCO1), and b-carotene-9 0 , 10 0 -oxygenase (BCO2) cleave lycopene to produce bioactive apo-lycopenoids. Although BCO1/BCO2 polymorphisms affect human and animal lycopene levels, whether dietary tomato consumption can inhibit high-fat diet (HFD)-promoted hepatocellular carcinoma (HCC) development and affect gut microbiota in the absence of BCO1/BCO2 is unclear. BCO1/BCO2 double knockout mice were initiated with a hepatic carcinogen (diethylnitrosamine) at 2 weeks of age. At 6 weeks of age, the mice were randomly assigned to an HFD (60% of energy as fat) with or without tomato powder (TP) feeding for 24 weeks. Results showed that TP feeding significantly decreased HCC development (67%, 83%, and 95% reduction in incidence, multiplicity, and tumor volume, respectively, P < 0.05). Protective effects of TP feeding were associated with (1) decreased hepatic inflammatory foci development and mRNA expression of proinflammatory biomarkers (IL1b, IL6, IL12a, monocyte chemoattractant protein-1, and inducible NO synthase); (2) increased mRNA expression of deacetylase sirtuin 1 and nicotinamide phosphoribosyltransferase involving NAD þ production; and (3) increased hepatic circadian clock genes (circadian locomotor output cycles kaput, period 2, and cryptochrome-2, Wee1). Furthermore, TP feeding increased gut microbial richness and diversity, and significantly decreased the relative abundance of the genus Clostridium and Mucispirillum, respectively. The present study demonstrates that dietary tomato feeding independent of carotenoid cleavage enzymes prevents HFD-induced inflammation with potential modulating gut microbiota and inhibits HFD-promoted HCC development. Cancer Prev Res; 11(12); 797-810. Ó2018 AACR. Effects of TP feeding on microbiota richness and distribution at phylum, genus, and species levels in DENþHFD-fed BCO1 À/À BCO2 À/À double KO mice. A, Observed OTUs, Chao1, and ACE, representing community richness. B, Shannon index, representing community evenness. C, Relative abundance of gram-positive bacteria or gram-negative bacteria. D, Relative abundance of major bacteria at phylum level. E and F, Relative abundance of major bacteria at genus, species levels. Ã Significantly different from the DENþHFD, P < 0.05. Xia et al. Acquisition of data (provided animals, acquired and managed patients, provided facilities, etc.): H. Xia, C. Liu, S. TakahashiAnalysis and interpretation of data (e.g., statistical analysis, biostatistics, computational analysis):

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Section: Methodsmentioning

confidence: 99%

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

Xia

et al. 2018

Cancer Prevention Research

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“…All animal protocols for the study were approved by the Institutional Animal Care and Use Committee at the USDA Human Nutrition Research Center on Aging (HNRCA) at Tufts University. Male BCO1 −/− BCO2 −/− double knock‐out (KO) mice were previously established by appropriate crossings . Mice were bred in an Association for Assessment and Accreditation of Laboratory Animal Care (AAALAC)‐accredited animal facility at the HNRCA at Tufts University.…”

Section: Methodsmentioning

confidence: 99%

“…Male BCO1 −/− BCO2 −/− double knock-out (KO) mice were previously established by appropriate crossings. [49] Mice were bred in an Association for Assessment and Accreditation of Laboratory Animal Care (AAALAC)-accredited animal facility at the HNRCA at Tufts University. All of mice were housed individually, in a controlled temperature and humidity room with 12-hour light/dark cycle and fed with standard chow diet (Harlan Laboratories, IN, USA).…”

Section: Animals Diets and Experimental Designmentioning

confidence: 99%

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

Fu³

et al. 2018

Molecular Nutrition Food Res

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“…It can be concluded from creatinine data, kidney weight, and kidney visuals that the additional treatment of β-carotene and emulsion at the tested concentration does not cause sub-chronic poisoning for up to 15 days of treatment. Furthermore, consumption of carotenoids at recommended concentrations does not overload liver metabolism and kidney 15 , so that it can be concluded that up to the 15 th day observation, the emulsion products tested are safe.…”

Section: Sub-chronic Toxicitymentioning

confidence: 98%

“…Several research explained that the consumption of carotene and zeaxanthin derived from corn caused an increase in the expression of several genes. 15,16 The downstream effects that arise consist of changes in weight, energy and fat metabolism, regulation of apoptosis, and tumor suppression. In addition, consumption of these two active compounds also causes a decrease in gene expression of enzymes responsible for oxidative Table 6.…”

Section: Body Weight Changes and General Observationsmentioning

confidence: 99%

Body Weight, Cholesterol Changes and Sub-Chronic Toxicity of Mice Treated with An Emulsion Product Rich in b-Carotene

Bohari

Lestari

Rahmadi

2020

Mol Cell Biomed Sci

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Background:One of the conditions for releasing standardized herbal medicines is the presence of pre-clinical testing that can be conducted with mice. Emulsion products with the main composition of pumpkin, red palm oil, and dragon fruit have high levels of β-carotene. The purpose of this study was to observe changes in weight, cholesterol, and sub-chronic toxicity from mice treated with emulsion products. Materials and Methods: Mice observed consisted of 6 groups: (1) untreated control (given standard ration); (2) negative control (given standard ration and 2.8% (v/b) egg yolk); (3) positive control (given standard ration and 0.4% (v/b) β-carotene); (4) standard ration, 0.4% (v/b) β-carotene and 2.8% (v/b) egg yolk; (5) given a standard ration and 2% (v/b) emulsion products; and (6) given a standard ration, 2% (v/b) emulsion products and 2.8% (v/b) egg yolk. Observations of sub-chronic toxicity were done by measuring creatinine levels, kidney weight, and visual observation of kidney swelling. Results: The use of β-carotene-rich emulsions does not cause a decrease in the average weight of mice. In general, β-carotene and emulsion can overcome cholesterol increases on the 7 th day, but not for the 15 th day as a result of standard food intake. The increase in creatinine levels only occurs in mice treated with egg yolk control. The additional treatment of β-carotene and emulsion successfully prevents the increase in creatinine levels. Conclusion: Emulsion products did not cause changes in weight, were able to reduce cholesterol levels in a limited manner and were not toxic to mice.

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Genetic dissection in a mouse model reveals interactions between carotenoids and lipid metabolism

Cited by 35 publications

References 50 publications

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

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

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

Body Weight, Cholesterol Changes and Sub-Chronic Toxicity of Mice Treated with An Emulsion Product Rich in b-Carotene

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