In the present study, HFD/STZ-mediated type 2 diabetic rodent model was used to comparatively evaluate coconut oil (CO) and thermally oxidized CO (TCO) as fat sources for the development of NAFLD. Female Wistar rats (six in each group; average bwt 200 g) fed HFD containing either CO or TCO for 2 months along with an intraperitoneal injection of streptozotocin (30 mg/kg bwt) at the end of 1-month feeding were found to develop fatty liver and subsequent inflammatory changes when compared to the normal laboratory diet-fed animals over 2-month period. Dyslipidemia as well as enhanced activities of serum hepatic marker enzymes (e.g., AST, ALT, and ALP) were prominent in TCO-fed animals. Further, HFD-fed animals showed alterations in their hepatic redox equilibrium. Hepatic GSH and antioxidant enzyme activities that form the part of a protective mechanism against oxidative/carbonyl stress were found to be increased in HFD-fed rats. Supporting this, CO- and TCO-containing-HFD-fed animals had enhanced lipid peroxidation (increased TBARs). Thus, fatty liver with heightened antioxidant defense, lipid peroxidation, and inflammation indicate hepatosteatosis. Histological details of the hepatic tissues corroborated sufficiently with these observations and showed an increased incidence of macrovesicles, inflammation, and hepatocyte ballooning in the TCO-fed rats than in CO-fed animals. Further, in support of this proposition, hydroxyproline, an index of collagen formation, was found to be significantly increased in TCO-fed rats than in the CO-fed group. Overall, the study shows that the formulation of HFD incorporated with TCO as a fat source, combined with STZ injection, is an efficient dietary model for developing hepatosteatosis with fibrotic stage in rats within 2 months. Administration of this modified diet for a more extended period may be a good model for cirrhotic and hepatocellular carcinoma studies, which need to be further assessed.

在本研究中，HFD/STZ 介导的 2 型糖尿病啮齿动物模型用于比较评估椰子油 (CO) 和热氧化 CO (TCO) 作为脂肪来源对 NAFLD 发展的影响。发现雌性 Wistar 大鼠（每组 6 只；平均体重 200 克）喂食含有 CO 或 TCO 的 HFD 2 个月，并在 1 个月喂食结束时腹膜内注射链脲佐菌素（30 毫克/千克体重）。与正常实验室饮食喂养的动物相比，脂肪肝和随后的炎症变化超过 2 个月。在喂食 TCO 的动物中，血脂异常以及血清肝标志物酶（如 AST、ALT 和 ALP）的活性增强是显着的。此外，喂食 HFD 的动物表现出肝脏氧化还原平衡的改变。发现在 HFD 喂养的大鼠中，肝脏 GSH 和抗氧化酶活性增加，这些活性构成对抗氧化/羰基应激的保护机制的一部分。支持这一点，含 CO 和 TCO 的 HFD 喂养动物的脂质过氧化增强（TBARs 增加）。因此，具有增强的抗氧化防御、脂质过氧化和炎症的脂肪肝表明肝脂肪变性。肝组织的组织学细节充分证实了这些观察结果，并显示 TCO 喂养的大鼠中大泡、炎症和肝细胞气球样变的发生率高于 CO 喂养的动物。此外，为了支持这一主张，发现在 TCO 喂养的大鼠中羟脯氨酸（一种胶原蛋白形成的指标）比在 CO 喂养的组中显着增加。全面的，研究表明，以 TCO 为脂肪源的 HFD 配方，结合 STZ 注射液，是大鼠 2 个月内发生肝脂肪变性伴纤维化阶段的有效饮食模型。延长这种改良饮食的管理时间可能是肝硬化和肝细胞癌研究的一个很好的模型，需要进一步评估。