The liver is responsible for many critical physiological processes, including nutrient metabolism, bile production, excretion, detoxification, immunity, vitamin storage, and so on [1, 2]. Liver fibrosis is a reaction to chronic injury or inflammation which produces scarring. If fibrosis is sustained, it may lead to advanced liver cirrhosis and hepatocellular carcinoma (HCC). Viral infection (such as hepatitis B virus and hepatitis C virus), alcohol abuse, non-alcoholic fatty liver disease, non-alcoholic steatohepatitis, autoimmune hepatitis, and cholestatic liver diseases can generate a chronic inflammatory microenvironment that may result in an abnormal wound healing response and the formation of collagen deposits. Hepatic stellate cells (HSCs) are the primary effector cells in liver fibrosis. HSCs maintain a non-proliferative, quiescent phenotype in the normal liver, but they may transdifferentiate into an activated phenotype in response to injury or damage to the liver [3]. Transforming growth factor (TGF)-β1 is the most potent fibrogenic cytokine in the liver. Once TGF-β binds to the receptor of HSCs, it induces phosphorylation of downstream smad proteins, resulting in the induction of collagen production [4], [5], [6], [7]. The activated form of HSCs secretes excess amounts of extracellular matrix (ECM) proteins, comprising collagen, fibronectin, and proteoglycans. The accumulation of ECM proteins forms a fibrous scar and destroys the hepatic architecture, resulting in liver cirrhosis and liver failure [8], [9], [10].

Common cooking methods include boiling, roasting, baking, frying, etc., all of which require the addition of fresh oil for cooking. Deep-frying is a fast and convenient method for food preparation. Most people like the texture and crispness of fried foods such as French fries, donuts, and fried chicken; therefore, the deep-frying method is common in homes and restaurants. However, these frying oils may be over-reused to save food cost, especially in traditional markets or night markets. During the frying processes, the temperature of the oil is high, which induces various chemical reactions, including hydrolysis, polymerization, lipid oxidation, and the Maillard reaction, and the frying process produces volatile/non-volatile compounds which darken the food's color, generate aromas, and develop unique textures [11, 12]. Total polar compounds (TPCs) are also generated during frying processes, including short-chain fatty acids, aldehydes, ketones, alcohols, and non-volatile products [13]. According to different oil types (such as soybean oil, sunflower oil, corn oil, olive oil, etc.), fried foods (dough, chicken nuggets, etc.), and the conditions (temperature) produce different chemicals, such as aldehydes, ketones, alcohols, carboxylic acid, furan, pyrazine, and pyridine [12]. Foods may absorb these toxic compounds during the frying process. Edible oils containing more saturated fatty acids, such as lard or palm oil, are usually more stable during frying processes. When there are more unsaturated fatty acids in the oil, such as in soybean oil, one of the most common oils used for frying in Taiwan, the deep frying process makes it unstable. The contents of TPCs increase with the frequency and duration of the frying process. Therefore, TPCs have been used to monitor the deterioration of frying oil [14]. According to the laws or regulations of frying oil, the maximum content of TPCs was set to 24% in Germany, 25% in Taiwan, France, Italy, Spain, and 27% in Australia and Switzerland [15].

The harmful effects of dietary oxidized frying oil have recently gradually been realized. In many studies, the consumption of repeatedly fried oil can cause genetic mutations and carcinogenesis in animals and humans [16]. Feeding fried oil and its polar substances to pregnant mice can cause teratogenesis and disrupt vitamin A metabolic gene expression in the fetal liver [17]. After feeding rats with repeatedly fried oil, polar compounds decreased expression of the estrogen receptor in the uterus and affected endocrine coordination by reducing activation of mitogen-activated protein kinase (MAPK) and Akt [18]. The use of oxidized frying oil in the diet also increases blood pressure and the concentration of angiotensin I-converting enzyme in the serum of rats, and hypertension is a critical risk factor for cardiovascular diseases [19]. Polar compounds from deep-fried oil disrupted lipid metabolism and glucose tolerance in Kunming mice [20]. However, the effects of dietary oxidized frying oil on HSCs activation and liver fibrosis are still unclear.