This study examined the effects of syringic acid (SA) on obese diet-induced hepatic dysfunction. Mice were fed high-fat diet (HFD) with or without SA (0.05%, wt/wt) for 16 weeks. SA reduced the body weight, visceral fat mass, serum levels of leptin, TNFα, IFNγ, IL-6 and MCP-1, insulin resistance, hepatic lipid content, droplets and early fibrosis, whereas it elevated the circulation of adiponectin. SA down-regulated lipogenic genes (Cidea, Pparγ, Srebp-1c, Srebp-2, Hmgcr, Fasn) and inflammatory genes (Tlr4, Myd88, NF-κB, Tnfα, Il6), whereas it up-regulated fatty acid oxidation genes (Pparα, Acsl, Cpt1, Cpt2) in the liver. SA also decreased hepatic lipogenic enzyme activities and elevated fatty acid oxidation enzyme activities relative to the HFD group. These findings suggested that dietary SA possesses anti-obesity, anti-inflammatory and anti-steatotic effects via the regulation of lipid metabolic and inflammatory genes. SA is likely to be a new natural therapeutic agent for obesity or non-alcoholic liver disease.
This study investigated the mechanism of processed tomato vinegar beverage (TVB)-mediated anti-obesity and anti-insulin resistance effects in high-fat diet (HF)-induced obese mice. Oral administration of TVB (14 mL kg(-1) body weight) to HF-fed mice for 6 weeks effectively reduced the body and visceral fat weight and significantly lowered plasma free fatty acid, triglyceride and hepatic triglyceride levels. TVB significantly increased fecal triglyceride excretion, both phosphorylated AMP-activated protein kinase (AMPK) and acetyl-CoA carboxylase (ACC) and peroxisome proliferator-activated receptor (PPAR)α protein levels in the liver, which were associated with increased fatty acid β-oxidation and carnitine palmitoyltransferase activities in HF-fed mice. TVB improved glucose tolerance, hyperinsulinemia and HOMA-IR levels in the HF + TVB group compared to the HF group. Additionally, TVB significantly increased glucokinase activity and decreased glucose-6-phosphatase activity in the liver, which enhanced glucose metabolism in obese mice. These results suggest that TVB prevents visceral obesity and insulin resistance via AMPK/PPARα-mediated fatty acid and glucose oxidation.
This study examined the effects of defatted mealworm fermentation extract (MWF) on alcoholic liver injury in rats. The rats were fed either a Lieber-DeCarli control (Con) or alcohol liquid diet (EtOH). The alcohol-fed rats were administered MWF (50, 100, or 200 mg/kg/day) and silymarin (200 mg/kg/day) orally for eight weeks. MWF prevented alcohol-induced hepatocellular damage by decreasing their serum aspartate transaminase, alanine transaminase, and gamma-glutamyl transpeptidase levels significantly compared to the EtOH group. MWF effectively reduced the relative hepatic weight, lipid contents, and fat deposition, along with the down-regulation of transcriptional factors and genes involved in lipogenesis compared to the EtOH group. It also enhanced the antioxidant defense system by elevating the glutathione level and glutathione reductase activity. MWF attenuated the alcohol-induced inflammatory response by down-regulating hepatic inflammation-associated proteins expression, such as phosphorylated-inhibitor of nuclear factor-kappa B-alpha and tumor necrosis factor-alpha, in chronic alcohol-fed rats. Furthermore, sequencing analysis in the colonic microbiota showed that MWF tended to increase Lactobacillus johnsonii reduced by chronic alcohol consumption. These findings suggest that MWF can attenuate alcoholic liver injury by regulating the lipogenic and inflammatory pathway and antioxidant defense system, as well as by partially altering the microbial composition.
We have previously showed that defatted mealworm fermentation extract (MWF) attenuates alcoholic liver injury by regulating lipid, inflammatory, and antioxidant metabolism in chronic alcohol-fed rats. The current metabolomics study was performed to monitor biochemical events following the administration of MWF (daily for eight weeks) to a rat model of alcoholic liver injury by gas chromatography-tandem mass spectrometry (GC-MS/MS). The levels of 15 amino acids (AAs), 17 organic acids (OAs), and 19 free fatty acids (FFAs) were measured in serum. Analysis of variance (ANOVA), principal component analysis (PCA), and partial least squares discriminant analysis (PLS-DA) were used to compare the levels of 51 metabolites in serum. In particular, 3-hydroxybutyric acid (3-HB), pyroglutamic acid (PG), octadecanoic acid, and docosahexaenoic acid (DHA) were evaluated as high variable importance point (VIP) scores and PCA loading scores as determined by PLS-DA and PCA, and these were significantly higher in the MWF and silymarin groups than in the EtOH group. MWF showed a protective effect from alcohol-induced liver damage by elevating hepatic β-oxidation activity, and serum 3-HB levels were significantly higher in the MWF group than in the EtOH control group. Glycine levels were higher in the MWF group than in the EtOH group, and PG levels (related to glutathione production) were also elevated, indicating a reduction in alcohol-related oxidative stress. In addition, MWF is protected from alcohol-induced inflammation and steatosis by increasing serum DHA, palmitic, and octadecanoic acid levels as compared with the EtOH group. These results suggest that MWF might attenuate alcoholic liver disease, due to its anti-inflammatory and antioxidant effects by up-regulating hepatic β-oxidation activity and down-regulating liver FFA uptake.
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