Department of Biochemistry, University of Wisconsin-Madison, 433 Babcock Drive, Madison, WI 53706, USA.
College of Science and Health Professions, King Saud Bin Abdulaziz University for Health Sciences, Riyadh 11564, Saudi Arabia.
Int J Mol Sci. 2022 Nov 24;23(23):14671. doi: 10.3390/ijms232314671.
Stearoyl-CoA desaturase-1 (SCD1) catalyzes the rate-liming step of monounsaturated fatty acid biosynthesis and is a key regulator of systemic glucose metabolism. Mice harboring either a global (GKO) or liver-specific deletion (LKO) of display enhanced insulin signaling and whole-body glucose uptake. Additionally, GKO and LKO mice are protected from high-carbohydrate diet-induced obesity. Given that high-carbohydrate diets can lead to chronic metabolic diseases such as obesity, diabetes, and hepatic steatosis, it is critical to understand how deficiency confers metabolically beneficial phenotypes. Here we show that insulin-like growth factor-binding protein 1 (IGFBP1), a hepatokine that has been reported to enhance insulin signaling, is significantly elevated in the liver and plasma of GKO and LKO mice fed a low-fat high-carbohydrate diet. We also observed that the expression of hepatic is regulated by oleic acid (18:1n9), a product of SCD1, through the mTORC1-FGF21 axis both in vivo and in vitro.
硬脂酰辅酶 A 去饱和酶-1（SCD1）催化单不饱和脂肪酸生物合成的限速步骤，是系统葡萄糖代谢的关键调节因子。携带 SCD1 全局（GKO）或肝脏特异性缺失（LKO）的小鼠显示出增强的胰岛素信号和全身葡萄糖摄取。此外，GKO 和 LKO 小鼠免受高碳水化合物饮食诱导的肥胖的影响。鉴于高碳水化合物饮食可导致肥胖症、糖尿病和肝脂肪变性等慢性代谢性疾病，了解 SCD1 缺乏如何赋予有益的代谢表型至关重要。在这里，我们表明胰岛素样生长因子结合蛋白 1（IGFBP1）是一种已报道可增强胰岛素信号的肝源激素，在喂食低脂高碳水化合物饮食的 GKO 和 LKO 小鼠的肝脏和血浆中显着升高。我们还观察到，通过 mTORC1-FGF21 轴，SCD1 的产物油酸（18:1n9）在体内和体外均调节肝脏中 SCD1 的表达。
