Project description:Type 2 diabetes (T2D) is a major chronic healthcare concern worldwide. Emerging evidence suggests that a histone-modification-mediated epigenetic mechanism underlies T2D. Nevertheless, the dynamics of histone marks in T2D have not yet been carefully analyzed. Using a mass spectrometry-based label-free and chemical stable isotope labeling quantitative proteomic approach, we systematically profiled liver histone post-translational modifications (PTMs) in a prediabetic high-fat diet-induced obese (DIO) mouse model. We identified 170 histone marks, 30 of which were previously unknown. Interestingly, about 30% of the histone marks identified in DIO mouse liver belonged to a set of recently reported lysine acylation modifications, including propionylation, butyrylation, malonylation, and succinylation, suggesting possible roles of these newly identified histone acylations in diabetes and obesity. These histone marks were detected without prior affinity enrichment with an antibody, demonstrating that the histone acylation marks are present at reasonably high stoichiometry. Fifteen histone marks differed in abundance in DIO mouse liver compared with liver from chow-fed mice in label-free quantification, and six histone marks in stable isotope labeling quantification. Analysis of hepatic histone modifications from metformin-treated DIO mice revealed that metformin, a drug widely used for T2D, could reverse DIO-stimulated histone H3K36me2 in prediabetes, suggesting that this mark is likely associated with T2D development. Our study thus offers a comprehensive landscape of histone marks in a prediabetic mouse model, provides a resource for studying epigenetic functions of histone modifications in obesity and T2D, and suggest a new epigenetic mechanism for the physiological function of metformin.
Project description:Inbred C57BL/6J mice differ in their susceptibility to diet-induced obesity. Comparison of the liver transcriptomes leads to genes that are involved in the development as well as the maintenance of fatty liver during the onset of obesity upon high fat diet feeding. Genes being upregulated in DIO responder can be seen as drivers of fatty liver development, while genes upregulated in DIO non-responder are most likely involved in the protection against fatty liver diseases.
Project description:Obesity and overweight are closely related to diet, and gut microbiota play an important role in body weight and human health. The aim of this study was to explore how Lactobacillus curvatus HY7601 and Lactobacillus plantarum KY1032 supplementation alleviate obesity by modulating the human gut microbiome. A randomized, double-blind, placebo-controlled study was conducted on 72 overweight individuals. Over a 12-week period, probiotic groups consumed 5×10^9 colony-forming units of HY7601 and KY1032), whereas the placebo group consumed the same product without probiotics. After treatment, the probiotic group displayed a reduction in body weight (p <0.001), visceral fat mass (p <0.025), and waist circumference (p <0.007), and an increase in adiponectin (p <0.046), compared with the placebo group. Additionally, HY7601 and KY1032 supplementation modulated bacterial gut microbiota characteristics and beta diversity by increasing Bifidobacteriaceae and Akkermansiaceae, and decreasing Prevotellaceae and Selenomonadaceae. In summary, HY7601 and KY1032 probiotics exert anti-obesity effects by regulating the gut microbiota; hence, they have therapeutic potential for preventing or alleviating obesity and overweight.
Project description:Transfer of modified fecal viromes improve blood glucose regulation and alleviates symptoms of metabolic dysfunction-associated fatty liver disease in an obesity male mouse model
Project description:Acute lung injury/acute respiratory distress syndrome (ALI/ARDS) is a life-threatening condition characterized by lung inflammation and damage. Mechanical ventilation can exacerbate this condition. The gut microbiome, known to impact health, might have implications for ALI/ARDS outcomes. This study aimed to investigate the effects of probiotics in a murine ALI model. Using a two-hit approach combining lipopolysaccharide-induced inflammation and mechanical ventilation-induced injury, a severe lung injury model was established in mice. Probiotics containing Bifidobacterium spp. were administered due to their known interactions with immune cells and immune pathway modulation. The effects of probiotic administration on lung inflammation severity were evalu ated through biochemical, and histological analyses of lung tissue, and single-cell RNA sequencing analysis. Probiotic administration increased Bifidobacterium spp. composition in the gut microbiota and mitigated lung damage and inflammation. Single-cell RNA sequencing revealed the stimulation of Anxa1high macrophages, possibly promoting anti-inflammatory responses.