Tilianin Protects against Nonalcoholic Fatty Liver Disease in Early Obesity Mice

Abstract

Non-alcoholic fatty liver disease (NAFLD) has emerged as one of the most frequent types of liver disease in pediatric populations with obesity. Tilianin has multiple biological activities including anti-inflammatory and antioxidant. Here, we aim to explore the functions and possible mechanisms of tilianin on NAFLD in obese children. A high-fat high-carbohydrate (HFHC) diet was used to feed 21-d-old mice. Tilianin was administered at a dose of 10 or 20 mg/kg daily. HFHC-fed mice gained weight, increased liver index. The liver showed hepatocyte ballooning, inflammatory infiltration, and steatosis. Elevated levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyl transpeptidase (GGT), low-density lipoprotein cholesterol (LDL-C) and total cholesterol (TC) and reduced the high-density lipoprotein choles- terol (HDL-C) level were found in HFHC-fed mice. Administration of tilianin significantly reduced these impairments. We further evaluated proteins related to lipid metabolism and observed that LXRα, SREBP-1c, FAS and ACC1 expression were blunted following tilianin administration. In addition, tilianin suppressed reactive oxygen species (ROS) overproduction and lipid peroxide 4-Hydroxynonenal expression, ascribed to its oxidative stress-modulating capacity. Tilianin also reversed the increase in F4/80 expression and proinflammatory cytokine levels. Of note, tilianin administration resulted in decreased protein levels of active caspase-1 and NOD-like receptor protein 3 (NLRP3) in HFHC-fed mice. Our study suggests that tilianin may ameliorate NAFLD in early obese mice by modulating lipids metabolism, oxidative stress, and inflammation, which may in part involve inhibiting NLRP3 inflammasome activation.

Estrogen Attenuates Diethylnitrosamine-Induced Hepatocellular Carcinoma in Female Rats <i>via</i> Modulation of Estrogen Receptor/FASN/CD36/IL-6 Axis

“…Furthermore, Knowles et al 64) suggested the possible mechanism by which ORS inhibits FASN expression via increase DNA damage-inducible transcript-4 (DDIT4) expression which down-regulates mammalian target of rapamycin (mTOR), a key activator of SREBP-1c, resulting in inhibition of SREBP-1c leading to decreased FASN expression. 65,66) The suppressive effect of ORS on SREBP-1c protein expression has also been documented by Chyau et al 67) in high-fat high-fructose diet mice. Data analysis of the present study post-IHC realization revealed the absent impact of ORS on CD36 expression and the clear inhibitory effect on FASN expression which is mainly linked to its alleviating influence on DEN-induced HCC markers away from its effect on CD36 expression.…”

The Influence of Emodin Succinyl Ethyl Ester on Non-alcoholic Steatohepatitis Induced by a Diet High in Fructose, Cholesterol, and Fat in Mice

“…NLRP3 expression was significantly increased in the liver tissues of NASH patients. In addition, the NLRP3 pathway plays an important role in the regulation of inflammation during the development of NASH 22) . Studies have also shown that the pathological process of NASH can be mitigated by inhibiting the NLRP3 pathway.…”