Hepatocyte-specific SLC27A4 deletion ameliorates nonalcoholic fatty liver disease in mice via suppression of phosphatidylcholine-mediated PXR activation.

Background: The protein Solute carrier family 27 member 4 (SLC27A4) is crucial for fatty acid synthesis and β-oxidation, but its role in hepatic steatosis and nonalcoholic fatty liver disease (NAFLD) progression is not fully understood.

Methods: Mice with AAV-mediated overexpression of Slc27a4 in liver and hepatocytes-specific deletion of Slc27a4 were fed a standard chow diet, a high-fat diet (HFD), or a methionine and choline-deficient diet (MCD). Serum and liver tissues were collected and analyzed by biochemical assay, histology, lipidomic analysis, RNA-seq analysis, qPCR, western blot and immunofluorescence.

Harnessing the Therapeutic Potential of Ginsenoside Rd for Activating SIRT6 in Treating a Mouse Model of Nonalcoholic Fatty Liver Disease.

Nonalcoholic fatty liver disease (NAFLD) is a prevalent global condition and a common precursor to liver cancer, yet there is currently no specific medication available for its treatment. Ginseng, renowned for its medicinal and dietary properties, has been utilized in NAFLD management, although the precise underlying mechanism remains elusive. To investigate the effectiveness of ginsenoside Rd, we employed mouse and cell models to induce NAFLD using high-fat diets, oleic acid, and palmitic acid.

Microglia Sirt6 modulates the transcriptional activity of NRF2 to ameliorate high-fat diet-induced obesity.

Background: Microglia play a pivotal role in neuroinflammation, while obesity triggers hypothalamic microglia activation and inflammation. Sirt6 is an important regulator of energy metabolism in many peripheral tissues and hypothalamic anorexic neurons. However, the exact mechanism for microglia Sirt6 in controlling high-fat diet-induced obesity remain unknown.

Pachymic acid modulates sirtuin 6 activity to alleviate lipid metabolism disorders.

Pachymic acid (Pac), a major bioactive constituent of , is an antioxidant that inhibits triglyceride (TG) accumulation. To the best of our knowledge, the present study investigated for the first time whether Pac activated sirtuin 6 (SIRT6) signaling to alleviate oleic acid (OA)-palmitic acid (PA)-induced lipid metabolism disorders in mouse primary hepatocytes (MPHs). In the present study, MPHs challenged with Pac were used to test the effects of Pac on intracellular lipid metabolism.

Ginsenoside Rc Modulates SIRT6-NRF2 Interaction to Alleviate Alcoholic Liver Disease.

Alcoholic liver disease (ALD) is a serious worldwide health problem. Ginsenoside Rc is a major active ingredient isolated from , whose pharmacological effects counteract oxidative stress, inflammation, and lipid accumulation. However, it is still unclear whether ginsenoside Rc might exert beneficial effects on alcohol-induced liver injury.

Ginsenoside Rc, as an FXR activator, alleviates acetaminophen-induced hepatotoxicity relieving inflammation and oxidative stress.

Acetaminophen (APAP) intake leads to excessive NAPQI deposition, stimulating inflammatory and oxidative stress and causing fatal liver injury. However, the detailed molecular mechanism involved is unknown, and effective therapeutic approaches remain insufficient. In this study, we discovered that treatment with ginsenoside Rc can prevent the inflammatory response caused by APAP and oxidative stress in mouse primary hepatocytes (MPHs), along with the corresponding changes in related genes.

Hepatic SIRT6 Modulates Transcriptional Activities of FXR to Alleviate Acetaminophen-induced Hepatotoxicity.

Background & Aims: Excessive acetaminophen (APAP) intake causes oxidative stress and inflammation, leading to fatal hepatotoxicity; however, the mechanism remains unclear. This study aims to explore the protective effects and detailed mechanisms of sirtuin 6 (SIRT6) in the defense against APAP-induced hepatotoxicity.

Methods: Hepatocyte-specific SIRT6 knockout mice, farnesoid X receptor (FXR) knockout mice, and mice with genetic or pharmacological activation of SIRT6 were subjected to APAP to evaluate the critical role of SIRT6 in the pathogenesis of acute liver injury.

A Sensitive Liquid Chromatography-Mass Spectrometry Method for Determination of Toosendanin in Rat Plasma and its Application to Pharmacokinetic Study.

A simple, rapid and sensitive analytical method was developed for the determination of toosendanin in rat plasma using liquid chromatography tandem mass spectrometry (LC-MS/MS). Andrographolide was selected as the internal standard, and the plasma samples were extracted by liquid-liquid extraction with diethyl ether. Chromatographic separation was performed on a Dikma Spursil C18, 3.

Emodin palliates high-fat diet-induced nonalcoholic fatty liver disease in mice via activating the farnesoid X receptor pathway.

Background: Cassia mimosoides Linn (CMD) is a traditional Chinese herb that clears liver heat and dampness. It has been widely administered in clinical practice to treat jaundice associated with damp-heat pathogen and obesity. Emodin (EMO) is a major bioactive constituent of CMD that has apparent therapeutic efficacy against obesity and fatty liver.