Conophylline inhibits high fat diet-induced non-alcoholic fatty liver disease in mice

Abstract

Conophylline (CnP), a vinca alkaloid extracted from the leaves of the tropical plant Tabernaemontana divaricate, attenuates hepatic fibrosis in mice. We have previously shown that CnP inhibits non-alcoholic steatohepatitis (NASH) using a methionine-choline-deficient (MCD) diet-fed mouse model. However, little is known about the CnP mediated inhibition of hepatic steatosis in high-fat diet-induced non-alcoholic fatty liver disease (NAFLD) mouse models. CnP (0.5 and 1 μg/g/body weight) was co-administered along with a high-fat diet to male BALB/c mice. After nine weeks of administering the high-fat diet, hepatic steatosis, triglyceride, and hepatic fat metabolism-related markers were examined. Administration of a high-fat diet for 9 weeks was found to induce hepatic steatosis. CnP dose-dependently attenuated the high-fat diet-induced hepatic steatosis. The diet also attenuated hepatic peroxisome proliferator-activated receptor alpha (PPARA) mRNA levels. PPARA is known to be involved in β-oxidation. CnP upregulated the mRNA levels of hepatic PPARA and its target genes, such as carnitine palmitoyl transferase 1 (CPT1) and CPT2, in a dose-dependent manner in the liver. Furthermore, levels of hepatic β-hydroxybutyrate, which is a type of ketone body, were increased by CnP in a dose-dependent manner. Finally, CnP increased the expression of the autophagosomal marker LC3-II and decreased the expression of p62, which are known to be selectively degraded during autophagy. These results indicate that CnP inhibits hepatic steatosis through the stimulation of β-oxidation and autophagy in the liver. Therefore, CnP might prove to be a suitable therapeutic target for NAFLD.

Beneficial Effect of Taraxacum coreanum Nakai via the Activation of LKB1-AMPK Signaling Pathway on Obesity

“…PPAR α expression was positively correlated with the expression of CPT-1. Namely, PPAR α regulates the levels of CPT-1, an enzyme essential for β -oxidation of long-chain fatty acids [ 35 , 36 ]. The present study indicated a similar tendency of PPAR α and CPT-1 expressions [ 37 , 38 ].…”

Effects of Curcumin in a Mouse Model of Very High Fat Diet-Induced Obesity

“…Fat-enriched diets providing 32–45% [ 55 , 56 , 57 , 58 ] or 60% kcal fat [ 59 , 60 , 61 , 62 , 63 ] are a well-established approach to NAFLD in rodents. However, in our model, evaluating the anti-NAFLD effects of curcumin was problematic.…”

Reversal of Increase in Intestinal Permeability by Mangifera indica Seed Kernel Extract in High-Fat Diet-Induced Obese Mice

“…Changing dietary habits and reduced physical activity has increased the incidences of NAFLD to an alarming proportion, and presently, 25% of the world’s population is affected by NAFLD. It is pertinent to note that the onset of NAFLD is considered as the hepatic response of metabolic syndrome and in the absence of any preventive measures, NAFLD can progress towards other irreversible liver complications such as NASH, liver fibrosis, cirrhosis, and hepatocellular carcinoma [ 30 , 31 ]. Liver is one of the principal organs involved in lipid metabolism, and abnormal functioning of cellular pathways involved in lipid deposition and lipid metabolism facilitates the accumulation of lipid in hepatocytes, leading to excessive lipid deposition in the liver [ 32 ].…”