The conversion of β-carotene to vitamin A in adipocytes drives the anti-obesogenic effects of β-carotene in mice.
The conversion of β-carotene to vitamin A in adipocytes drives the anti-obesogenic effects of β-carotene in mice.
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DOI：
10.1016/j.molmet.2022.101640
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发表时间：
2022-12
影响因子：
8.1
通讯作者：
Amengual, Jaume
中科院分区：
文献类型：
--
作者：
Coronel, Johana;Yu, Jianshi;Pilli, Nageswara;Kane, Maureen A.;Amengual, Jaume
β-胡萝卜素加氧酶1 （BCO1）是负责将β-胡萝卜素裂解为视网膜的酶，视网膜是维生素A形成的第一个中间体。临床前研究表明，BCO1的表达是膳食β-胡萝卜素影响脂质代谢所必需的。本研究的目的是产生一种基因治疗策略，在脂肪组织中过度表达BCO1，并利用储存在脂肪细胞中的β-胡萝卜素产生维生素a，减少肥胖。我们生成了一种新的脂肪组织特异性的腺相关载体，在小鼠脂肪细胞中过表达BCO1 （AT-AAV-BCO1）。我们使用一种独特的模型来测试该载体，以实现β-胡萝卜素在脂肪组织中的积累，其中Bco1 - / -小鼠喂食β-胡萝卜素。以过表达绿色荧光蛋白的AT-AAV为对照。我们评估了适当的递送途径，并优化了载体的细胞和器官特异性、剂量和暴露。我们还采用形态计量学分析来评估BCO1表达在肥胖中的影响，以及HPLC和质谱法来定量组织中β-胡萝卜素和类维甲酸，包括维甲酸。在小鼠脂肪组织中注入AT-AAV-BCO1导致维甲酸的产生，维甲酸是一种维生素a的代谢物，对基因调控有很强的影响。AT-AAV-BCO1处理也使脂肪组织大小和脂肪细胞面积分别减少35%和30%。这些影响是性别特异性的，突出了哺乳动物维生素A代谢的复杂性。通过递送AT-AAV-BCO1， BCO1的过表达导致脂肪细胞中β-胡萝卜素转化为维生素A，从而导致肥胖的减少。这些研究首次强调了脂肪组织β-胡萝卜素作为BCO1过表达靶标在减少肥胖中的潜力。β-胡萝卜素加氧酶1 （BCO1）裂解β-胡萝卜素生成维生素a。我们构建脂肪组织载体，研究BCO1在脂肪细胞中过表达的影响。雌性小鼠脂肪细胞过表达BCO1产生维甲酸，导致脂肪组织大小减小。
The β-carotene oxygenase 1 (BCO1) is the enzyme responsible for the cleavage of β-carotene to retinal, the first intermediate in vitamin A formation. Preclinical studies suggest that BCO1 expression is required for dietary β-carotene to affect lipid metabolism. The goal of this study was to generate a gene therapy strategy that over-expresses BCO1 in the adipose tissue and utilizes the β-carotene stored in adipocytes to produce vitamin A and reduce obesity. We generated a novel adipose-tissue-specific, adeno-associated vector to over-express BCO1 (AT-AAV-BCO1) in murine adipocytes. We tested this vector using a unique model to achieve β-carotene accumulation in the adipose tissue, in which Bco1−/− mice were fed β-carotene. An AT-AAV over-expressing green fluorescent protein was utilized as control. We evaluated the adequate delivery route and optimized cellular and organ specificity, dosage, and exposure of our vectors. We also employed morphometric analyses to evaluate the effect of BCO1 expression in adiposity, as well as HPLC and mass spectrometry to quantify β-carotene and retinoids in tissues, including retinoic acid. AT-AAV-BCO1 infusions in the adipose tissue of the mice resulted in the production of retinoic acid, a vitamin A metabolite with strong effects on gene regulation. AT-AAV-BCO1 treatment also reduced adipose tissue size and adipocyte area by 35% and 30%, respectively. These effects were sex-specific, highlighting the complexity of vitamin A metabolism in mammals. The over-expression of BCO1 through delivery of an AT-AAV-BCO1 leads to the conversion of β-carotene to vitamin A in adipocytes, which subsequently results in reduction of adiposity. These studies highlight for the first time the potential of adipose tissue β-carotene as a target for BCO1 over-expression in the reduction of obesity. β-carotene oxygenase 1 (BCO1) cleaves β-carotene to form vitamin A. We generated an adipose tissue vector to study the effect of BCO1 over-expression in the adipocyte. Female mice over-expressing BCO1 in the adipocyte generated retinoic acid, and as a result, the adipose tissue size was reduced.
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中央杏仁核中CRF的持续AAV介导的过表达降低了与尼古丁戒断相关的抑郁状态。
影响因子：
6.8
作者：
Qi X;Shan Z;Ji Y;Guerra V;Alexander JC;Ormerod BK;Bruijnzeel AW
通讯作者：
Bruijnzeel AW
DOI：
10.1073/pnas.93.24.14082
发表时间：
1996-11-26
影响因子：
11.1
作者：
Kessler, PD;Podsakoff, GM;Byrne, BJ
通讯作者：
Byrne, BJ
影响因子：
82.9
作者：
通讯作者：
--
影响因子：
3.3
作者：
Cohen P;Spiegelman BM
通讯作者：
Spiegelman BM
影响因子：
3.8
作者：
Durinikova E;Kozovska Z;Poturnajova M;Plava J;Cierna Z;Babelova A;Bohovic R;Schmidtova S;Tomas M;Kucerova L;Matuskova M
通讯作者：
Matuskova M