Association between 12α-hydroxylated bile acids and hepatic steatosis in rats fed a high-fat diet
Association between 12α-hydroxylated bile acids and hepatic steatosis in rats fed a high-fat diet
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DOI：
10.1016/j.jnutbio.2020.108412
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发表时间：
2020-09-01
影响因子：
5.6
通讯作者：
Ishizuka, Satoshi
中科院分区：
文献类型：
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作者：
Hori, Shota;Abe, Takayuki;Ishizuka, Satoshi
高脂肪（HF）饮食诱导肝脂肪变性，这是肥胖、2型糖尿病和心血管疾病等非传染性疾病的风险因素。之前，我们发现大鼠喂食HF会增加粪便胆汁酸（BA）的排泄，特别是12 α-羟基化（12 α OH）BA。虽然肝脏是我们身体的代谢中心，但HF喂养大鼠中肝脏脂肪变性与12 α OH BAs之间的关联并不清楚。因此，我们广泛研究了HF喂养大鼠的BA组成，并评估了肝脂肪变性和12 α OH BA之间的关联。将驯化的雄性近交系WKAH/HkmSlc大鼠分为两组，饲喂对照或HF饮食8周。喂食HF饮食增加肝脏甘油三酯和总胆固醇浓度，这与粪便、门静脉血浆和肝脏中的12 α OH BAs浓度呈正相关，但与非12 α OH BAs无关。伴随着12 α OH BAs的增加，喂食HF饮食的大鼠表现出增加的脂肪吸收和更高的肝脏Cidea mRNA表达。12 α-OH-BA分泌的增加可能通过促进膳食脂肪的吸收和肝脏Cidea mRNA的表达而促进肝脂肪变性。12 α OH BA的增加与肝脏胆固醇7 α-羟化酶（Cyp 7a 1）和甾醇12 α-羟化酶（Cyp 8b 1）mRNA表达增强相关。在HF喂养的大鼠的肝脏中，7 α-羟基胆固醇（BA的前体）显著增加。总之，这些数据表明，HF饮食通过利用积累的肝脏胆固醇和增强肝脏中Cyp 7a 1和Cyp 8b 1的mRNA表达来优先增加12 α OH BAs的合成。(C)2020爱思唯尔公司All rights reserved.
High-fat (HF) diet induces hepatic steatosis that is a risk factor for noncommunicable diseases such as obesity, type 2 diabetes and cardiovascular disease. Previously, we found that HF feeding in rats increases the excretion of fecal bile acids (BAs), specifically 12 alpha-hydroxylated (12 alpha OH) BAs. Although the liver is the metabolic center in our body, the association between hepatic steatosis and 12 alpha OH BAs in HF-fed rats is undear. Thus, we investigated extensively BA composition in HF-fed rats and evaluated the association between hepatic steatosis and 12 alpha OH BAs. Acclimated male inbred WKAH/HkmSlc rats were divided into two groups and fed either control or HF diet for 8 weeks. Feeding HF diet increased hepatic triglyceride and total cholesterol concentrations, which correlated positively with 12 alpha OH BAs concentrations but not with non-12 alpha OH BAs in the feces, portal plasma and liver. Accompanied by the increase in 12 alpha OH BAs, the rats fed HF diet showed increased fat absorption and higher mRNA expression of liver Cidea. The enhancement of 12 alpha OH BA secretion may contribute to hepatic steatosis by the promotion of dietary fat absorption and hepatic Cidea mRNA expression. The increase in 12 alpha OH BAs was associated with enhanced liver cholesterol 7 alpha-hydroxylase (Cyp7a1) and sterol 12 alpha-hydroxylase (Cyp8b1) mRNA expression. There was a significant increase in 7 alpha-hydroxycholesterol, a precursor of BAs, in the liver of HF-fed rats. Altogether, these data suggest that the HF diet increases preferentially 12 alpha OH BAs synthesis by utilizing the accumulated hepatic cholesterol and enhancing mRNA expression of Cyp7a1 and Cyp8b1 in the liver. (C) 2020 Elsevier Inc. All rights reserved.