Raspberry polysaccharides attenuate hepatic inflammation and oxidative stress in diet-induced obese mice by enhancing butyrate-mediated intestinal barrier function.

Obesity and associated liver diseases are becoming global public health challenges. Raspberry (Rubus chingii Hu.), as a medicine food homology plant, possesses a series of health-promoting properties, but its protective effect on obesity-related liver injury and the potential mechanisms remain obscure. Herein high-fat diet (HFD)-fed mice were orally treated with raspberry polysaccharides (RCP) for 14 weeks. Treatment with RCP alleviated obesity and associated symptoms including hyperglycemia, hyperlipemia, endotoxemia, as well as hepatic inflammation and oxidant stress in HFD-induced obese mice. RCP restructured the gut microbiota and host metabolism especially by increasing the levels of Dubosiella and its metabolite butyrate. Besides, exogenous butyrate supplementation protected against intestinal barrier disruption, and thereby reduced inflow of lipopolysaccharide and mitigated inflammation and oxidative injury in the liver of obese mice. Therefore, we suggest that RCP can be utilized as a novel prebiotics to improve obesity-induced hepatic oxidative injury by enhancing butyrate-mediated intestinal barrier function.

A novel polysaccharide from Rubus chingii Hu unripe fruits: Extraction optimization, structural characterization and amelioration of colonic inflammation and oxidative stress.

Raspberry is used as a medicine food homology species and its polysaccharides are worthy being investigated and developed. In the present study, a novel polysaccharide of unripe raspberry fruits (pRCP) was extracted and characterized. The results show that pRCP was an acidic heteropolysaccharide and its Mw value was 74.86 kDa with a high homogeneity. The main chain of pRCP consisted of â†’ 3,6)-ß-Galp(1 â†’ and â†’ 5)-α-Araf(1→, and its side chain was composed of α-Araf(1 â†’ linked to the C3 position of â†’ 3,6)-ß-Galp(1 â†’. In addition, pRCP supplementation increased the gut microbial diversity and reduced harmful bacteria including Erysipelatoclostridium and Negativibacillus in high-fat diet (HFD)-fed mice. Treatment with pRCP also alleviated HFD-induced colonic inflammation and oxidative stress in mice. These beneficial effects can be transferred to recipient mice by faecal microbiota transplantation from pRCP-treated mice. Therefore, our study suggests that pRCP could be used as a potential prebiotics to improve intestinal health by modulating the gut microbiota.

Optimized integration of metabolomics and lipidomics reveals brain region-specific changes of oxidative stress and neuroinflammation in type 1 diabetic mice with cognitive decline.

INTRODUCTION: Type 1 diabetes (T1D) causes cognitive decline and has been associated with brain metabolic disorders, but its potential molecular mechanisms remain unclear. OBJECTIVES: The purpose of this study was to explore the molecular mechanisms underlying T1D-induced cognitive impairment using metabolomics and lipidomics. METHODS: We developed an optimized integration approach of metabolomics and lipidomics for brain tissue based on UPLC-Q-TOF-MS and analyzed a comprehensive characterization of metabolite and lipid profiles in the hippocampus and frontal cortex of T1D male mice with cognitive decline (T1DCD) and age-matched control (CONT) mice. RESULTS: The results show that T1DCD mice had brain metabolic disorders in a region-specific manner relative to CONT mice, and the frontal cortex exhibited a higher lipid peroxidation than the hippocampus in T1DCD mice. Based on metabolic changes, we found that microglia was activated under diabetic condition and thereby promoted oxidative stress and neuroinflammation, leading to neuronal injury, and this event was more pronounced in the frontal cortex than the hippocampus. CONCLUSION: Our results suggest that brain region-specific shifts in oxidative stress and neuroinflammation may contribute to diabetic cognitive decline, and the frontal cortex could be the more vulnerable brain region than the hippocampus.

Targeting Gut Microbiota and Host Metabolism with Dendrobium officinale Dietary Fiber to Prevent Obesity and Improve Glucose Homeostasis in Diet-Induced Obese Mice.

SCOPE: Obesity is becoming a major public health problem due to excess dietary fat intake. Dendrobium officinale (D. officinale) is a medicine food homology plant and exerts multiple health-promoting effects. However, its antiobesity effects and the potential mechanisms remain unclear. METHODS AND RESULTS: High-fat diet (HFD)-fed mice are administered D. officinale dietary fiber (DODF) daily by gavage for 11 weeks. The results show that treatment with DODF alleviates obesity, liver steatosis, inflammation, and oxidant stress in HFD-induced obese mice. Improved glucose homeostasis in obese mice after DODF treatment is achieved by enhancing insulin pathway and hepatic glycogen synthesis. DODF restructures the gut microbiota in obese mice by decreasing the relative abundance of Bilophila and increasing the relative abundances of Akkermansia, Bifidobacterium, and Muribaculum. Also, DODF reshapes the metabolic phenotype of obese mice as indicated by up-regulating energy metabolism, increasing acetate and taurine, and reducing serum low density/very low density lipoproteins (LDL/VLDL). These beneficial effects are partly transferred by FMT, implying the gut microbiota as a target for the protective effect of DODF on obesity-related symptoms. CONCLUSION: The results suggest that DODF can be used as a novel prebiotics to maintain the gut microbial homeostasis and improve metabolic health, preventing obesity and related metabolic syndrome.

Sex-specific metabolic alterations in the type 1 diabetic brain of mice revealed by an integrated method of metabolomics and mixed-model.

Type 1 diabetes (T1D) can cause brain region-specific metabolic disorders, but whether gender influences T1D-related brain metabolic changes is rarely reported. Therefore, here we examined metabolic changes in six different brain regions of male and female mice under normal and T1D conditions using an integrated method of NMR-based metabolomics and linear mixed-model, and aimed to explore sex-specific metabolic changes from normal to T1D. The results demonstrate that metabolic differences occurred in all brain regions between two genders, while the hippocampal metabolism is more likely to be affected by T1D. At the 4th week after streptozotocin treatment, brain metabolic disorders mainly occurred in the cortex and hippocampus in female T1D mice, but the striatum and hippocampus in male T1D mice. In addition, anaerobic glycolysis was significantly altered in male mice, mainly in the striatum, midbrain, hypothalamus and hippocampus, but not in female mice. We also found that female mice exhibited a hypometabolism status relative to male mice from normal to T1D. Collectively, this study suggests that T1D affected brain region-specific metabolic alterations in a sex-specific manner, and may provide a metabolic view on diabetic brain diseases between genders.

Sex-Specific Metabolic Changes in Peripheral Organs of Diabetic Mice.

Diabetes mellitus (DM) can cause systemic metabolic disorders, but the impact of gender on DM-related metabolic changes is rarely reported. Herein, we analyzed metabolic alterations in the heart, liver, and kidney of male and female mice from normal to diabetes via a 1H NMR-based metabolomics method and aimed to investigate sex-specific metabolic mechanisms underlying the onset and development of diabetes and its complications. Our results demonstrate that male mice had more significant metabolic disorders from normal to diabetes than female mice. Moreover, the kidney was found as the major organ of metabolic disorders during the development of diabetes, followed by the liver and heart. These altered metabolites were mainly implicated in energy metabolism as well as amino acid, choline, and nucleotide metabolism. Therefore, this study suggests that the kidney is the primary organ affected by diabetes in a sex-specific manner, which provides a metabolic view on the pathogenesis of diabetic kidney diseases between genders.