Hepatic stearoyl-CoA desaturase-1 deficiency protects mice from carbohydrate-induced adiposity and hepatic steatosis
Hepatic stearoyl-CoA desaturase-1 deficiency protects mice from carbohydrate-induced adiposity and hepatic steatosis
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DOI：
10.1016/j.cmet.2007.10.014
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发表时间：
2007-12-01
期刊：
影响因子：
29
通讯作者：
Ntambi, James M.
中科院分区：
文献类型：
--
作者：
Miyazaki, Makoto;Flowers, Matthew T.;Ntambi, James M.
硬脂酰辅酶A去饱和酶-1(SCD1)是能量代谢的重要调节因子，催化合成单不饱和脂肪。为了了解SCD1在能量平衡中的组织特异性作用，我们使用Cre-lox技术产生了肝脏特异性SCD1基因敲除的小鼠(LKO)。LKO小鼠受到保护，免受高碳水化合物的影响，但不保护高脂肪(HF)、饮食诱导的肥胖和肝脏脂肪变性。此外，在高蔗糖、极低脂(HSVLF)饮食中，LKO小鼠的肝脏脂肪生成以及核SREBP-1和ChREBP水平显著低于SCD(lox/lox)(Lox)小鼠。在LKO小鼠中，HSVLF喂养导致低血糖和肝脏碳水化合物减少，这是由于糖异生障碍所致。补充油酸盐，但不是硬脂酸盐，可使LKO小鼠的肥胖、糖异生、甘油三酯分泌和肝脏脂肪生成正常化。这些结果表明，碳水化合物诱导的肥胖需要肝脏SCD1的表达(因此，油酸)，但肝外组织中的SCD1抑制是保护小鼠免受HF诱导的肥胖和胰岛素抵抗的需要。
Stearoyl-CoA desaturase-1 (SCD1), a critical regulator of energy metabolism, catalyzes the synthesis of monounsaturated fats. To understand the tissue-specific role of SCD1 in energy homeostasis, we used Cre-lox technology to generate mice with a liver-specific knockout of Scd1 (LKO). LKO mice were protected from high-carbohydrate, but not high-fat (HF), dietinduced adiposity and hepatic steatosis. Additionally, on a high-sucrose, very low-fat (HSVLF) diet, lipogenesis and levels of nuclear SREBP-1 and ChREBP were significantly decreased in the livers of LKO relative to Scd1(lox/lox) (Lox) mice. HSVLF feeding in LKO mice caused hypoglycemia and hepatic carbohydrate reduction due to an impairment of gluconeogenesis. Oleate, but not stearate, supplementation normalized adiposity, gluconeogenesis, triglyceride secretion, and hepatic lipogenesis of LKO mice. These results indicate that hepatic SCD1 expression (and thus, oleate) is required for carbohydrate-induced adiposity, but SCD1 inhibition in extrahepatic tissues is required to protect mice from HF-induced obesity and insulin resistance.