The natural compounds, Magnolol or Honokiol, promote adipose tissue browning and resist obesity through modulating PPARα/γ activity.

Non-alcoholic fatty liver disease (NAFLD) is closely associated with the body's energy metabolism. A potential strategy to regulate energy metabolism, combat obesity, and reduce NAFLD is by enhancing adipocyte thermogenesis and increasing energy expenditure. In this study, our objective was to examine the effects of phenolic extracts derived from Magnolia officinalis on the regulation of NAFLD. Specifically, we investigated the impact of Magnolol or Honokiol treatment on high-fat diet (HFD)-induced obese C57BL6/J male mice. Firstly, we monitored energy metabolism, dissected tissues, and analyzed tissue sections. Additionally, we conducted experiments on HepG2 and primary adipocytes to gain insights into the roles of Magnolol or Honokiol. To further understand the effects of these compounds on related signaling pathways and marker genes, we performed molecular docking, dual-luciferase assays, and interfered with target genes. Our findings revealed that Magnolol or Honokiol activate the peroxisome proliferator activated receptor alpha (PPARα) signaling pathway, leading to the alleviation of NAFLD. This activation promotes fatty acid oxidation, reduces lipogenesis, and enhances the expression and secretion of FGF21. Notably, Fibroblast growth factor 21 (FGF21), secreted by the liver, plays a crucial role in improving communication between the liver and adipocytes while also promoting the browning of adipose tissue. Additionally, Magnolol or Honokiol activate the peroxisome proliferator activated receptor gamma (PPARγ) signaling pathway, resulting in increased uncoupling protein 1 (UCP1) expression, heightened heat production in adipose tissue, and anti-obesity. Therefore, Magnolol or Honokiol alleviate NAFLD, promote adipose tissue browning and resist obesity through dual activation of PPARα/γ.

Dietary supplementation of magnolol alleviates fatty liver hemorrhage syndrome in postpeak Xinhua laying hens via regulation of liver lipid metabolism.

As a metabolic disease, fatty liver hemorrhagic syndrome (FLHS) has emerged as a major cause of noninfectious mortality in laying hens, resulting in substantial economic losses to the poultry industry. This study aimed to investigate the therapeutic effects of magnolol on FLHS in postpeak laying hen model, focusing on lipid metabolism, antioxidative capacity, and potential molecular mechanisms of action. We selected 150 Xinhua laying hens aged 50 wk and divided them into normal diet group (ND), high-fat diet group (HFD), 100 mg/kg magnolol group (MG100), 300 mg/kg magnolol group (MG300), 500 mg/kg magnolol group (MG500) on average. The experiment lasted for 6 wk, and liver samples were collected from the hens at the end of the experiment. The results demonstrated that the inclusion of magnolol in the diet had a significant impact on various factors. It led to a reduction in weight, an increase in egg production rate, a decrease in blood lipid levels, and an improvement in abnormal liver function, liver steatosis, and oxidative stress. These effects were particularly prominent in the MG500 group. The RNA-Seq analysis demonstrated that in the MG500 group, there was a down-regulation of genes associated with fatty acid synthesis (Acc, Fasn, Scd, Srebf1, Elovl6) compared to the HFD group. Moreover, genes related to fatty acid oxidation (CPT1A and PGC1α) were found to be up-regulated. The Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis of these differentially expressed genes indicated their enrichment in the PPAR signaling pathway. These findings demonstrate that magnolol can mitigate FLHS by inhibiting fatty acid synthesis and promoting fatty acid oxidation. This discovery offers a novel approach for treating FLHS in laying hens, reducing the economic losses associate with FLHS.

Dietary Selenium Alleviated Mouse Liver Oxidative Stress and NAFLD Induced by Obesity by Regulating the KEAP1/NRF2 Pathway.

Nonalcoholic fatty liver disease (NAFLD) occurs when excess fat is stored in the liver and it is strongly linked with metabolic syndrome and oxidative stress. Selenium (Se) is an essential micronutrient in animals, which has a variety of biological functions, including antioxidant and anti-inflammatory. However, the exact effect of dietary selenium on NAFLD and the underlying molecular mechanism are not yet clear. Herein, we fed a high-fat diet (HFD) to C57BL/6 mice to construct an in vivo NAFLD model, treated AML-12 cells with palmitic acid (PA) to construct an in vitro NAFLD model, and AML-12 cells were stimulated with H2O2 to induce hepatocyte oxidative stress and then treated with adequate selenium. We observed that adequate selenium significantly improved the hepatic injury and insulin resistance in HFD mice, and decreased the fat accumulation and the expression of lipogenic genes in PA-induced AML-12 cells. Meanwhile, selenium significantly inhibited the production of reactive oxygen species (ROS), inhibited apoptosis, and restored mitochondrial number and membrane potential in PA- induced AML-12 cells. In addition, selenium can promote selenoproteinP1 (SEPP1) synthesis to regulate the Kelch-like ECH-associated protein 1 (KEAP1)/NF-E2-related factor 2 (NRF2) pathway, so as to defend against hepatocyte oxidative stress. These findings suggest that dietary selenium supplementation can effectively resist hepatic injury and insulin resistance during NAFLD development, and regulate the KEAP1/NRF2 pathway to resist oxidative stress by promoting SEPP1 synthesis.

Sirt1 Promotes the Restoration of Hepatic Progenitor Cell (HPC)-Mediated Liver Fatty Injury in NAFLD Through Activating the Wnt/ß-Catenin Signal Pathway.

Non-alcoholic fatty liver disease (NAFLD) has developed into the world's largest chronic epidemic. In NAFLD, hepatic steatosis causes hepatocytes dysfunction and even apoptosis. The liver has a strong restoration or regeneration ability after an injury, however, it is unclear through which pattern fatty liver injury in NAFLD is repaired and what the repair mechanism is. Here, we found that in the high-fat diet (HFD)-induced NAFLD mice model, fatty liver injury caused the significant ductular reaction (DR), which is a marker to promote the repair of liver injury. SOX9+ and HNF4α+ biphenotype also suggested that hepatic progenitor cells (HPCs) were activated by fatty liver injury in the HFD-elicited NAFLD mice model. Concurrently, fatty liver injury also activated the Wnt/ß-catenin signal pathway, which is a necessary process for HPC differentiation into mature hepatocytes. However, Sirt1 knockdown weakened HPC activation and Wnt/ß-catenin signal in Sirt1+/- mice with HFD feeding. In rat-derived WB-F344 hepatic stem cell line, Sirt1 overexpression (OE) or Sirt1 activator-Resveratrol promoted HPC differentiation via activating Wnt/ß-catenin signal pathway. Glycogen PAS staining demonstrated that Sirt1 OE promoted WB-F344 cells to differentiate into mature hepatocytes with glycogen synthesis ability, while Sirt1 inhibitor EX527 or Wnt/ß-catenin pathway inhibitor HF535 decreased glycogen positive cells. Together, our data suggested that Sirt1 plays a vital role in activating HPCs to repair fatty liver injury or promote liver regeneration through the Wnt/ß-catenin signal pathway in NAFLD, which might provide a new strategy for fatty liver injury or NAFLD therapy.