Nobiletin (NOB) is a naturally occurring compound, commonly found in citrus peel, that shows hepatoprotective and lipid-reducing effects. However, the lipid biomarkers and the potential improvement mechanisms have not been adequately explored. Therefore, we investigated the ameliorative effect and the molecular mechanism of NOB on NAFLD induced by a high-fat diet in mice. The results showed that supplementation with NOB over 12 weeks markedly improved glucose tolerance, serum lipid profiles, inflammatory factors, hepatic steatosis, and oxidative stress. These beneficial effects were mainly related to reduced levels of potential lipid biomarkers including free fatty acids, diacylglycerols, triacylglycerols, and cholesteryl esters according to hepatic lipidomic analysis. Twenty lipids, including DGs and phosphatidylcholines, were identified as potential lipid biomarkers. Furthermore, RT-qPCR and Western blot analysis indicated that NOB inhibited the expression of lipogenesis-related factors such as SREBP-1c, SCD-1, and FAS, and upregulated the expression of lipid oxidation (PPARα) and cholesterol conversion (LXRα, CYP7A1, and CYP27A1) genes as well as antioxidation-related factors (Nucl-Nrf2, NQO1, HO-1, and GCLC), indicating that NOB intake may reduce lipid biosynthesis and increase lipid consumption to improve hepatic steatosis and oxidative stress. This study is beneficial for understanding the ameliorative effects of NOB on NAFLD.

Diabetes Mellitus (DM) is a complicated metabolic illness defined by hyperglycemia due to faulty insulin production or activity, and it is one of the world’s fastest-growing public health concerns. The construction of a good diabetes mellitus model is crucial for diabetes mellitus pathophysiology research, diabetic mellitus prevention, and the development of effective therapeutic therapy. Diabetes mellitus models are now chemically induced, spontaneous, and genetically created. The models were created using the chemical induction of streptozotocin and alloxan, and the spontaneous type of diabetes mellitus animal models are appropriate for T1DM, T2DM, and related phenotypes, including obesity and insulin resistance. Genetically engineered animal models are much more closely related to human diabetes mellitus, including gene knockout animal models. They can be used to explain the cause of diabetes mellitus in terms of molecular mechanisms and to study the effects of individual genes on insulin secretion and insulin resistance faultlessly. This research provides a detailed description of T1DM and T2DM animal models, illustrating the importance of diabetes mellitus.