HOPE Cardiometabolic Research Team & Department of Physiology, Faculty of Basic Medical Sciences, University of Ilorin, Ilorin, Nigeria.
Department of Physiology, College of Medicine and Health Sciences, Afe Babalola University, Ado-Ekiti, Nigeria.
Can J Physiol Pharmacol. 2019 Nov;97(11):1042-1052. doi: 10.1139/cjpp-2019-0037. Epub 2019 Jul 23.
The present study investigated the effects of oral ethinylestradiol-levonorgestrel (EEL) on hepatic lipid and glycogen contents during high fructose (HF) intake, and determined whether pyruvate dehydrogenase kinase-4 (PDK-4) and glucose-6-phosphate dehydrogenase (G6PD) activity were involved in HF and (or) EEL-induced hepatic dysmetabolism. Female Wistar rats weighing 140-160 g were divided into groups. The control, EEL, HF, and EEL+HF groups received water (vehicle, p.o.), 1.0 μg ethinylestradiol plus 5.0 μg levonorgestrel (p.o.), fructose (10% ), and EEL plus HF, respectively, on a daily basis for 8 weeks. Results revealed that treatment with EEL or HF led to insulin resistance, hyperinsulinemia, increased hepatic uric acid production and triglyceride content, reduced glycogen content, and reduced production of plasma or hepatic glutathione- and G6PD-dependent antioxidants. HF but not EEL also increased fasting glucose and hepatic PDK-4. Nonetheless, these alterations were attenuated by EEL in HF-treated rats. Our results demonstrate that hepatic lipid accumulation and glycogen depletion induced by HF is accompanied by increased PDK-4 and defective G6PD activity. The findings also suggest that EEL would attenuate hepatic lipid accumulation and glycogen depletion by suppression of PDK-4 and enhancement of a G6PD-dependent antioxidant barrier.
本研究探讨了口服炔雌醇-左炔诺孕酮（EEL）在高果糖（HF）摄入期间对肝脂质和糖原含量的影响，并确定丙酮酸盐脱氢酶激酶-4（PDK-4）和葡萄糖-6-磷酸脱氢酶（G6PD）活性是否参与 HF 和（或）EEL 诱导的肝代谢障碍。140-160 克重的雌性 Wistar 大鼠分为以下几组：对照组、EEL 组、HF 组和 EEL+HF 组，分别接受水（赋形剂，口服）、1.0 μg 乙炔雌二醇加 5.0 μg 左炔诺孕酮（口服）、果糖（10%）和 EEL 加 HF，每天一次，持续 8 周。结果表明，EEL 或 HF 治疗导致胰岛素抵抗、高胰岛素血症、肝尿酸生成和甘油三酯含量增加、糖原含量减少以及血浆或肝谷胱甘肽和 G6PD 依赖性抗氧化剂生成减少。HF 但不是 EEL 还增加了空腹血糖和肝 PDK-4。然而，这些变化在 HF 治疗大鼠中被 EEL 减弱。我们的结果表明，HF 诱导的肝脂质积累和糖原耗竭伴随着 PDK-4 的增加和 G6PD 活性的缺陷。研究结果还表明，EEL 通过抑制 PDK-4 和增强 G6PD 依赖性抗氧化屏障来减轻肝脂质积累和糖原耗竭。
