Anti-NAFLD Effect of Djulis Hull and Its Major Compound, Rutin, in Mice with High-Fat Diet (HFD)-Induced Obesity

Abstract

Nonalcoholic fatty liver disease (NAFLD) has become the main cause of chronic liver disease worldwide, and the increasing trend of NAFLD has burdened the healthcare system. NAFLD encompasses a wide range of liver pathologies, from simple benign hepatocyte steatosis to more severe inflammatory nonalcoholic steatohepatitis. Djulis (Chenopodium formosanum Koidz.) is traditionally used as a native cereal and a food supplement that promotes human health through its antioxidant, hepatoprotection, skin protection, hypolipidemic, hypoglycemic, and antitumor effects. Djulis hull, regarded as agricultural waste, is usually removed during food processing and contains high rutin content. The present study evaluated the anti-NAFLD effect of Djulis hull and its major compound, rutin, in mice with high-fat diet (HFD)-induced obesity. Male C57BL/6J mice were randomly divided into one of five diet groups (n = 6 per group) and fed the following for 16 weeks: (1) normal diet group (ND), (2) HFD group (HFD), (3) HFD and oral gavage of low dose (50 mg/kg) of Djulis hull crude extract group (HFD/LCE), (4) HFD and oral gavage of high dose (250 mg/kg) of Djulis hull crude extract group (HFD/HCE), or (5) HFD and oral gavage (50 mg/kg) of rutin (HFD/R) group. We found that Djulis hull crude extract markedly reduced HFD-induced elevation in body weight and fat around the kidney weights, hepatic injury indicators (AST and ALT), and steatosis and hypertrophy. Furthermore, Djulis hull crude extract administration significantly affected DG(20:4/18:1), PA(22:0/17:1), PC(10:0/17:0), and PA(18:4/20:5) in HFD-induced obese mice. In addition, treating HFD-induced obese rats with Djulis hull crude extract significantly increased fatty acid oxidation by increasing the protein expression of phosphorylated AMP-activated protein kinase, peroxisome proliferator-activated receptor-α, and hepatic carnitine palmitoyltransferase-1 in the liver. Moreover, the administration of Djulis hull crude extract significantly decreased the inflammatory response (PPARγ, IL-6, and TNF-α) to modulate oxidative damage. Therefore, Djulis hull crude extract attenuated the progression of NAFLD by reducing inflammation mediated by PPARγ and enhancing the expression levels of genes involved in fatty acid oxidation mediated by AMPK signaling.