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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.
J Nutr. 2015 Feb; 145(2):268-76.JN

Abstract

BACKGROUND

Nonalcoholic fatty liver disease is positively associated with obesity and cardiovascular disease risk. Apo-10'-lycopenoic acid (APO10LA), a potential oxidation product of apo-10'-lycopenal that is generated endogenously by β-carotene-9',10'-oxygenase (BCO2) cleavage of lycopene, inhibited hepatic steatosis in BCO2-expressing mice.

OBJECTIVE

The present study evaluated lycopene and APO10LA effects on hepatic steatosis in mice without BCO2 expression.

METHODS

Male and female BCO2-knockout (BCO2-KO) mice were fed a high saturated fat diet (HSFD) with or without APO10LA (10 mg/kg diet) or lycopene (100 mg/kg diet) for 12 wk.

RESULTS

Lycopene or APO10LA supplementation reduced hepatic steatosis incidence (78% and 72%, respectively) and severity in BCO2-KO male mice. Female mice did not develop steatosis, had greater hepatic total cholesterol (3.06 vs. 2.31 mg/g tissue) and cholesteryl ester (1.58 vs. 0.86 mg/g tissue), but had lower plasma triglyceride (TG) (229 vs. 282 mg/dL) and cholesterol (97.1 vs. 119 mg/dL) than male mice. APO10LA-mitigated steatosis in males was associated with reduced hepatic total cholesterol (18%) and activated sirtuin 1 signaling, which resulted in reduced fatty acids (FAs) and TG synthesis markers [stearoyl-coenzyme A (CoA) desaturase protein, 71%; acetyl-CoA carboxylase phosphorylation, 79%; AMP-activated protein kinase phosphorylation, 67%], and elevated cholesterol efflux genes (cytochrome P450 family 7A1, 65%; ATP-binding cassette transporter G5/8, 11%). These APO10LA-mediated effects were not mimicked by lycopene supplementation. Intriguingly, steatosis inhibition by lycopene induced peroxisome proliferator-activated receptor (PPAR)α- and PPARγ-related genes in mesenteric adipose tissue (MAT) that increases mitochondrial uncoupling [cell death-inducing DNA fragmentation factor, α subunit-like effector a, 55%; PR domain-containing 16, 47%; uncoupling protein 3 (Ucp3), 55%], FA β-oxidation (PPARα, 53%; very long chain acyl-CoA dehydrogenase, 38%), and uptake (FA transport protein 4, 29%; lipoprotein lipase 43%). Expressions of 10 MAT PPAR-related genes were inversely correlated with steatosis score, suggesting that lycopene reduced steatosis by increasing MAT FA utilization.

CONCLUSIONS

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.

Authors+Show Affiliations

Nutrition and Cancer Biology Laboratory, Friedman School of Nutrition Science and Policy, Tufts University, Boston, MA; and.Nutrition and Cancer Biology Laboratory.Cardiovascular Nutrition Laboratory, Jean-Mayer USDA Human Nutrition Research Center on Aging, and Friedman School of Nutrition Science and Policy, Tufts University, Boston, MA; and.Department of Pharmacology, School of Medicine, Case Western Reserve University, Cleveland, OH.Nutrition and Cancer Biology Laboratory, Friedman School of Nutrition Science and Policy, Tufts University, Boston, MA; and xiang-dong.wang@tufts.edu.

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, U.S. Gov't, Non-P.H.S.

Language

eng

PubMed ID

25644347

Citation

Ip, Blanche C., et al. "Lycopene and Apo-10'-lycopenoic Acid Have Differential Mechanisms of Protection Against Hepatic Steatosis in Β-carotene-9',10'-oxygenase Knockout Male Mice." The Journal of Nutrition, vol. 145, no. 2, 2015, pp. 268-76.
Ip BC, Liu C, Lichtenstein AH, et al. Lycopene and apo-10'-lycopenoic acid have differential mechanisms of protection against hepatic steatosis in β-carotene-9',10'-oxygenase knockout male mice. J Nutr. 2015;145(2):268-76.
Ip, B. C., Liu, C., Lichtenstein, A. H., von Lintig, J., & Wang, X. D. (2015). Lycopene and apo-10'-lycopenoic acid have differential mechanisms of protection against hepatic steatosis in β-carotene-9',10'-oxygenase knockout male mice. The Journal of Nutrition, 145(2), 268-76. https://doi.org/10.3945/jn.114.200238
Ip BC, et al. Lycopene and Apo-10'-lycopenoic Acid Have Differential Mechanisms of Protection Against Hepatic Steatosis in Β-carotene-9',10'-oxygenase Knockout Male Mice. J Nutr. 2015;145(2):268-76. PubMed PMID: 25644347.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Lycopene and apo-10'-lycopenoic acid have differential mechanisms of protection against hepatic steatosis in β-carotene-9',10'-oxygenase knockout male mice. AU - Ip,Blanche C, AU - Liu,Chun, AU - Lichtenstein,Alice H, AU - von Lintig,Johannes, AU - Wang,Xiang-Dong, Y1 - 2014/12/10/ PY - 2015/2/4/entrez PY - 2015/2/4/pubmed PY - 2015/3/24/medline KW - PPAR KW - carotenoid metabolism KW - hepatic cholesterol KW - lipid metabolism KW - mesenteric adipose tissue KW - mitochondrial uncoupling KW - nonalcoholic fatty liver disease KW - obesity KW - plasma lipids KW - sirtuin 1 SP - 268 EP - 76 JF - The Journal of nutrition JO - J. Nutr. VL - 145 IS - 2 N2 - BACKGROUND: Nonalcoholic fatty liver disease is positively associated with obesity and cardiovascular disease risk. Apo-10'-lycopenoic acid (APO10LA), a potential oxidation product of apo-10'-lycopenal that is generated endogenously by β-carotene-9',10'-oxygenase (BCO2) cleavage of lycopene, inhibited hepatic steatosis in BCO2-expressing mice. OBJECTIVE: The present study evaluated lycopene and APO10LA effects on hepatic steatosis in mice without BCO2 expression. METHODS: Male and female BCO2-knockout (BCO2-KO) mice were fed a high saturated fat diet (HSFD) with or without APO10LA (10 mg/kg diet) or lycopene (100 mg/kg diet) for 12 wk. RESULTS: Lycopene or APO10LA supplementation reduced hepatic steatosis incidence (78% and 72%, respectively) and severity in BCO2-KO male mice. Female mice did not develop steatosis, had greater hepatic total cholesterol (3.06 vs. 2.31 mg/g tissue) and cholesteryl ester (1.58 vs. 0.86 mg/g tissue), but had lower plasma triglyceride (TG) (229 vs. 282 mg/dL) and cholesterol (97.1 vs. 119 mg/dL) than male mice. APO10LA-mitigated steatosis in males was associated with reduced hepatic total cholesterol (18%) and activated sirtuin 1 signaling, which resulted in reduced fatty acids (FAs) and TG synthesis markers [stearoyl-coenzyme A (CoA) desaturase protein, 71%; acetyl-CoA carboxylase phosphorylation, 79%; AMP-activated protein kinase phosphorylation, 67%], and elevated cholesterol efflux genes (cytochrome P450 family 7A1, 65%; ATP-binding cassette transporter G5/8, 11%). These APO10LA-mediated effects were not mimicked by lycopene supplementation. Intriguingly, steatosis inhibition by lycopene induced peroxisome proliferator-activated receptor (PPAR)α- and PPARγ-related genes in mesenteric adipose tissue (MAT) that increases mitochondrial uncoupling [cell death-inducing DNA fragmentation factor, α subunit-like effector a, 55%; PR domain-containing 16, 47%; uncoupling protein 3 (Ucp3), 55%], FA β-oxidation (PPARα, 53%; very long chain acyl-CoA dehydrogenase, 38%), and uptake (FA transport protein 4, 29%; lipoprotein lipase 43%). Expressions of 10 MAT PPAR-related genes were inversely correlated with steatosis score, suggesting that lycopene reduced steatosis by increasing MAT FA utilization. CONCLUSIONS: 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. SN - 1541-6100 UR - https://www.unboundmedicine.com/medline/citation/25644347/Lycopene_and_apo_10'_lycopenoic_acid_have_differential_mechanisms_of_protection_against_hepatic_steatosis_in_β_carotene_9'10'_oxygenase_knockout_male_mice_ L2 - https://academic.oup.com/jn/article-lookup/doi/10.3945/jn.114.200238 DB - PRIME DP - Unbound Medicine ER -