Dataset Information

Loss of Hepatocyte-Specific PPAR? Expression Ameliorates Early Events of Steatohepatitis in Mice Fed the Methionine and Choline-Deficient Diet.

ABSTRACT: The prevalence of nonalcoholic fatty liver disease (NAFLD) is increasing worldwide. To date, there is not a specific and approved treatment for NAFLD yet, and therefore, it is important to understand the molecular mechanisms that lead to the progression of NAFLD. Methionine- and choline-deficient (MCD) diets are used to reproduce some features of NAFLD in mice. MCD diets increase the expression of hepatic peroxisome proliferator-activated receptor gamma (PPAR?, Pparg) and the fatty acid translocase (CD36, Cd36) which could increase hepatic fatty acid uptake and promote the progression of NAFLD in mice and humans. In this study, we assessed the contribution of hepatocyte-specific PPAR? and CD36 expression to the development of early events induced by the MCD diet. Specifically, mice with adult-onset, hepatocyte-specific PPAR? knockout with and without hepatocyte CD36 overexpression were fed a MCD diet for three weeks. Hepatocyte PPAR? and/or CD36 expression did not contribute to the development of steatosis induced by the MCD diet. However, the expression of inflammatory and fibrogenic genes seems to be dependent on the expression of hepatocyte PPAR? and CD36. The expression of PPAR? and CD36 in hepatocytes may be relevant in the regulation of some features of NAFLD and steatohepatitis.

SUBMITTER: Cordoba-Chacon J

PROVIDER: S-EPMC7211257 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Loss of Hepatocyte-Specific PPARγ Expression Ameliorates Early Events of Steatohepatitis in Mice Fed the Methionine and Choline-Deficient Diet.

Cordoba-Chacon Jose J

PPAR research 20200501

The prevalence of nonalcoholic fatty liver disease (NAFLD) is increasing worldwide. To date, there is not a specific and approved treatment for NAFLD yet, and therefore, it is important to understand the molecular mechanisms that lead to the progression of NAFLD. Methionine- and choline-deficient (MCD) diets are used to reproduce some features of NAFLD in mice. MCD diets increase the expression of hepatic peroxisome proliferator-activated receptor gamma (PPARγ, Pparg) and the fatty ...[more]

PMID: 32411189

Similar Datasets

Project description:BackgroundNonalcoholic steatohepatitis (NASH), a liver disease caused by a nonalcoholic fatty liver, is increasing in incidence worldwide. Owing to the complexity of its pathogenic mechanisms, there are no therapeutic agents for this disease yet. The ideal drug for NASH needs to concurrently decrease hepatic lipid accumulation and exert anti-inflammatory, antifibrotic, and antioxidative effects in the liver. Because of their multipurpose therapeutic effects, we considered that medicinal herbs are suitable for treating patients with NASH.MethodsWe determined the efficacy of the alcoholic extract of Lysimachia vulgaris var. davurica (LV), an edible medicinal herb, for NASH treatment. For inducing NASH, C57BLKS/J lar-Leprdb/Leprdb (db/db) male mice were fed with a methionine-choline deficient (MCD) diet ad libitum. After 3 weeks, the LV extract and a positive control (GFT505) were administered to mice by oral gavage for 3 weeks with a continued MCD diet as needed.ResultsIn mice with diet-induced NASH, the LV extract could relieve the disease symptoms; that is, the extract ameliorated hepatic lipid accumulation and also showed antioxidative and anti-inflammatory effects. The LV extract also activated nuclear factor E2-related factor 2 (Nrf2) expression, leading to the upregulation of antioxidants and detoxification signaling. Moreover, the extract presented remarkable efficacy in alleviating liver fibrosis compared with GFT505. This difference was caused by significant LV extract-mediated reduction in the mRNA expression of fibrotic genes like the alpha-smooth muscle actin and collagen type 3 alpha 1. Reduction of fibrotic genes may thus relate with the downregulation of transforming growth factor beta (TGFβ)/Smad signaling by LV extract administration.ConclusionsLipid accumulation and inflammatory responses in the liver were alleviated by feeding LV extract to NASH-induced mice. Moreover, the LV extract strongly prevented liver fibrosis by blocking TGFβ/Smad signaling. Hence, LV showed sufficient potency for use as a therapeutic agent against NASH.

Dataset Information

Loss of Hepatocyte-Specific PPAR? Expression Ameliorates Early Events of Steatohepatitis in Mice Fed the Methionine and Choline-Deficient Diet.

Publications

Loss of Hepatocyte-Specific PPAR<i>γ</i> Expression Ameliorates Early Events of Steatohepatitis in Mice Fed the Methionine and Choline-Deficient Diet.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets