Abstract
A high-fat diet (HFD) is one of the main causes of obesity and metabolic diseases. The liver is particularly affected by HFD causing metabolic dysfunction associated with fatty liver disease. Therefore, different strategies are used to mitigate the negative effects of HFD. This study aimed to assess the protective effects of walnut extract against HFD-induced toxicity in mice. The mice were fed HFD and walnut extract alone or in combination. The walnut extract was analyzed for composition using high-performance liquid chromatography with a diode array detector (HPLC-DAD) and ultra-high-performance liquid chromatography with mass spectrometry (UHPLC-MS/MS). Serum lipid profile; liver histology; hepatic antioxidants such as catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), lipid peroxidation (TBARS), and reduced glutathione (GSH); inflammatory markers like IL-6 and TNF-α; and phospholipids were determined. Results showed that phenolic acids, epicatechin, catechin, benzaldehyde, and juglone were the main constituents in the extract. The HFD group showed increased hepatic fat accumulation as evidenced by biochemical and histopathological examinations compared to the control animals. The HFD group mice also showed increased body and cardiac weights, modified lipid profiles, decreased antioxidant status, and increased levels of hepatic inflammatory markers. The weights of the body and heart, lipid profiles, antioxidant contents (CAT, SOD, GSH-Px, TBARS, and GSH), and pro-inflammatory cytokines (IL-6 and TNF-α) were all normalized by consuming walnut extract. Similarly, the HFD group had significantly high amounts of hepatic lipase, phospholipid, and lysophospholipid levels, which were improved by walnut extract. In conclusion, walnut extract has been shown to play a unique role in promoting the recovery of liver damage caused by a high-fat diet.