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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 ?g/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 ?-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 ?-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 ?-oxidation and autophagy in the liver. Therefore, CnP might prove to be a suitable therapeutic target for NAFLD.

SUBMITTER: Ohashi T

PROVIDER: S-EPMC6349312 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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

Ohashi Tomohiko T Nakade Yukiomi Y Ibusuki Mayu M Kitano Rena R Yamauchi Taeko T Kimoto Satoshi S Inoue Tadahisa T Kobayashi Yuji Y Sumida Yoshio Y Ito Kiyoaki K Nakao Haruhisa H Umezawa Kazuo K Yoneda Masashi M

PloS one 20190128 1

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-admi ...[more]

PMID: 30689650

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

Publications

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

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