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

Oleh:

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

Jenis: Article from Journal - ilmiah internasional
Dalam koleksi: JN: The Journal of Nutrition vol. 145 no. 02 (Feb. 2015), page 267-276.
Topik: nonalcoholic fatty liver disease; hepatic cholesterol; lipid metabolism; sirtuin 1; obesity; plasma lipids; mitochondrial uncoupling; PPAR; carotenoid metabolism; mesenteric adipose tissue

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Perpustakaan FK Nomor Panggil: J42.K Non-tandon: 1 (dapat dipinjam: 0) Tandon: tidak ada

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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 ß-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)a- and PPAR?-related genes in mesenteric adipose tissue (MAT) that increases mitochondrial uncoupling [cell death–inducing DNA fragmentation factor, a subunit-like effector a, 55%; PR domain-containing 16, 47%; uncoupling protein 3 (Ucp3), 55%], FA ß-oxidation (PPARa, 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.

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