Lycopene and Apo-10′-lycopenoic Acid Have Differential Mechanisms of Protection against Hepatic Steatosis in β-Carotene-9′,10′-oxygenase Knockout Male Mice

Ip, Blanche C.; Liu, Chun; Lichtenstein, Alice H.; Lintig, Johannes von; Wang, Xiang Dong

doi:10.3945/jn.114.200238

Cited by 49 publications

(45 citation statements)

References 64 publications

(103 reference statements)

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“…Our results showed that supplementation with lycopene or TP for 12 weeks ameliorated the hepatic steatosis induced by HFD, which is consistent with several studies that demonstrated the amelioration of hepatosteatosis under lycopene or tomato products effect . The protective effects of lycopene and TP in hepatosteatosis may be related to multiple mechanisms , including anti‐oxidant/anti‐inflammatory effects and lipid metabolism modulation . In agreement, we reported an anti‐inflammatory effect of lycopene or TP in the liver but also an impact on lipid metabolism.…”

Section: Discussionsupporting

confidence: 92%

Lycopene and tomato powder supplementation similarly inhibit high-fat diet induced obesity, inflammatory response, and associated metabolic disorders

Fenni

Hammou

Astier

et al. 2017

Mol. Nutr. Food Res.

115

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Scope: Several studies have linked the high intake of lycopene or tomatoes products with lower risk for metabolic diseases. The aim of the present study was to evaluate and to compare the effect of lycopene and tomato powder on obesity associated disorders. Methods and results:Male C57BL/J6 mice were assigned into 4 groups to receive: control diet (CD), high fat diet (HFD), high fat diet supplemented with lycopene or with tomato powder (TP) for 12 weeks. In HFD condition, lycopene and TP supplementation significantly reduced adiposity index, organ and relative organ weights, serum triglycerides, free fatty acids, 8-iso-prostaglandin GF2α and improved glucose homeostasis, but did not affect total body weight. Lycopene and TP supplementation prevented HFD-induced hepatosteatosis and hypertrophy of adipocytes. Lycopene and TP decreased HFD-induced pro-inflammatory cytokine mRNA expression in the liver and in the epididymal adipose tissue. The antiinflammatory effect of lycopene and TP was related to a reduction in the phosphorylation levels of IκB, and p65, and resulted in a decrease of inflammatory proteins in adipose tissue Conclusion:These results suggest that lycopene or TP supplementation display similar beneficial health effects that could be particularly relevant in the context of nutritional approaches to fight obesity-associated pathologies.

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Section: Discussionsupporting

confidence: 92%

Lycopene and tomato powder supplementation similarly inhibit high-fat diet induced obesity, inflammatory response, and associated metabolic disorders

Fenni

Hammou

Astier

et al. 2017

Mol. Nutr. Food Res.

115

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“…Thus, this pattern suggests that lycopene cleavage metabolites produced by BCO2 may have anti-prostate-cancer bioactivity and that their production is diminished in the Bco2−/− mice. Previous studies on the effect of the lycopene metabolite, apo-10’-lycopenoic acid, have shown it to reduce hepatic inflammation, steatosis, and tumorigenesis in mice (60, 61), and other studies of apo-8’-lycopenal in models of liver cancer have been indicative of bioactivity (38, 39), increasing the plausibility of lycopene metabolite activity in the prostate. We also demonstrate that tomato-fed Bco2−/− accumulate lycopene precursors, phytofluene, zeta-carotene, and a suggestion for phytoene, opening the door for hypotheses regarding the potential for BCO2 to cleave additional carotenoids.…”

Section: Discussionmentioning

confidence: 99%

β-Carotene 9′,10′ Oxygenase Modulates the Anticancer Activity of Dietary Tomato or Lycopene on Prostate Carcinogenesis in the TRAMP Model

Tan

Thomas‐Ahner

Moran

et al. 2017

Cancer Prevention Research

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The hypothesis that dietary tomato consumption or the intake of the carotenoid lycopene inhibits prostate cancer arose from epidemiologic studies and is supported by preclinical rodent experiments and in vitro mechanistic studies. We hypothesize that variation in activity of carotenoid cleavage enzymes, such as β-carotene 9’,10’-oxygenase (BCO2), may alter the impact of dietary tomato and lycopene on prostate carcinogenesis and therefore examined this relationship in the TRAMP model. Starting at three weeks of age, TRAMP:Bco2+/+ and TRAMP:Bco2−/− mice were fed either AIN-93G control, or semi-purified diets containing 10% tomato powder or 0.25% lycopene beadlets until 18 weeks of age. Both tomato- and lycopene-fed TRAMP:Bco2−/− mice had significantly greater serum concentrations of total, 5-cis, other cis, and all-trans lycopene than TRAMP:Bco2+/+ mice. Tomato- and lycopene-fed mice had a lower incidence of prostate cancer compared to the control-fed mice. While Bco2 genotype alone did not significantly change prostate cancer outcome in the control AIN-93G-fed mice, the abilities of lycopene and tomato feeding to inhibit prostate carcinogenesis were significantly attenuated by the loss of Bco2 (interaction p=0.0004 and p=0.0383, respectively). Overall, dietary tomato and lycopene inhibited the progression of prostate cancer in TRAMP in a Bco2 genotype-specific manner, potentially implicating the anticancer activity of lycopene cleavage products. This study suggests that genetic variables impacting carotenoid metabolism and accumulation can impact anti-cancer activity and that future efforts devoted to understanding the interface between tomato carotenoid intake, host genetics, and metabolism will be necessary to clearly elucidate their interactive roles in human prostate carcinogenesis.

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“…Martín-Pozuelo et al [24] described a decrease in urinary isoprostranes and an over-expression of genes related to mitochondrial and peroxisomal fatty acid oxidation in rats with steatosis that had drunk tomato juice (HL group). In general, other authors, using different experimental designs, have reported a beneficial effect of tomato or lycopene consumption on NAFLD, by reduction of the oxidative stress and also improvement of the lipid metabolism, exerting a preventive effect on the progression to NASH [22,23,25]. …”

Section: Discussionmentioning

confidence: 99%

“…Moreover, lycopene has been found to be a most effective antioxidant for liver health [20], showing different beneficial effects on liver metabolism in rats with induced NAFLD. Related to this, different authors have described, in animal models, a preventive effect of tomato consumption on steatosis, increasing mitochondrial and peroxisomal fatty acid oxidation [21,22,23,24], that could prevent the development of NASH due to the inhibitory effect of lipid peroxidation in the liver tissue [25,26]. …”

Section: Introductionmentioning

confidence: 99%

Tomato Juice Consumption Modifies the Urinary Peptide Profile in Sprague-Dawley Rats with Induced Hepatic Steatosis

Martín‐Pozuelo

González‐Barrio

Barberá

et al. 2016

IJMS

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Non-alcoholic fatty liver disease (NAFLD) is the most common liver disorder in Western countries, with a high prevalence, and has been shown to increase the risk of type 2 diabetes, cardiovascular disease (CVD), etc. Tomato products contain several natural antioxidants, including lycopene—which has displayed a preventive effect on the development of steatosis and CVD. Accordingly, the aim of the present work was to evaluate the effect of tomato juice consumption on the urinary peptide profile in rats with NAFLD induced by an atherogenic diet and to identify potential peptide biomarkers for diagnosis. Urine samples, collected weekly for four weeks, were analyzed by capillary electrophoresis (CE) coupled to a mass spectrometer (MS). A partial least squares-discriminant analysis (PLS-DA) was carried out to explore the association between differential peptides and treatments. Among the 888 peptides initially identified, a total of 55 were obtained as potential biomarkers. Rats with steatosis after tomato juice intake showed a profile intermediate between that of healthy rats and that of rats with induced hepatic steatosis. Accordingly, tomato products could be considered as a dietary strategy for the impairment of NAFLD, although further research should be carried out to develop a specific biomarkers panel for NAFLD.

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Lycopene and Apo-10′-lycopenoic Acid Have Differential Mechanisms of Protection against Hepatic Steatosis in β-Carotene-9′,10′-oxygenase Knockout Male Mice

Abstract: Our data suggest that lycopene and APO10LA inhibit HSFD-induced steatosis in BCO2-KO male mice through differential mechanisms. Sex disparity of BCO2-KO mice was observed in the outcomes of HSFD-induced liver steatosis and plasma lipids.

Cited by 49 publications

References 64 publications

Lycopene and tomato powder supplementation similarly inhibit high-fat diet induced obesity, inflammatory response, and associated metabolic disorders

Lycopene and tomato powder supplementation similarly inhibit high-fat diet induced obesity, inflammatory response, and associated metabolic disorders

β-Carotene 9′,10′ Oxygenase Modulates the Anticancer Activity of Dietary Tomato or Lycopene on Prostate Carcinogenesis in the TRAMP Model

Tomato Juice Consumption Modifies the Urinary Peptide Profile in Sprague-Dawley Rats with Induced Hepatic Steatosis

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