RESUMO
OBJECTIVES: Obesity can induce dysbiosis in the gut microbiota and is considered a separate risk factor for kidney function decline. Nonetheless, the precise function of intestinal microorganisms in facilitating the connection between obesity and kidney function decline remains uncertain. Hence, the objective of this study was to investigate the alterations in the gut microbiota composition that take place during obesity and their correlations with renal function utilizing a rat model. METHODS: For 20 weeks, 25 Sprague-Dawley rats were fed either a high-fat diet (HFD) or a normal-fat normal diet (ND). Physiological indices, peripheral plasma, kidney tissue, and colon contents were collected for comparison between groups. Metagenomic analysis of intestinal flora was performed. RESULTS: The HFD group demonstrated significantly increased levels of creatinine and urea nitrogen in the peripheral blood. Additionally, the HFD rats exhibited a significantly larger glomerular diameter compared to the ND group, accompanied by the presence of glomerulosclerosis, tubular vacuolar transformation, and other pathological changes in certain glomeruli. Metagenomics analysis revealed a notable rise in the prevalence of the Firmicutes phylum within the HFD group, primarily comprising the Rumenococcus genus. Functional analysis indicated that the gut microbiota in the HFD group primarily correlated with infectious diseases, signal transduction, and signaling molecules and interactions. CONCLUSIONS: This study provides evidence that the consumption of a HFD induces modifications in the composition and functionality of the gut microbiome in rats, which may serve as a potential mechanism underlying the relationship between obesity and the progression of kidney function decline.
Assuntos
Microbioma Gastrointestinal , Nefropatias , Ratos , Animais , Camundongos , Microbioma Gastrointestinal/fisiologia , Ratos Sprague-Dawley , Obesidade/complicações , Dieta Hiperlipídica/efeitos adversos , Nefropatias/complicações , Rim , Camundongos Endogâmicos C57BLRESUMO
BACKGROUND: Various studies have reported that individuals with membranous nephropathy (MN) exhibit an elevated susceptibility to cancers. However, a causal relationship has not been clearly established. METHODS: We constructed a genetic score that predicts MN by utilizing genetic variants linked to this condition as instrumental variables. These genetic scores were then compared with lung, colon, breast, and prostate cancer risks by a two-sample Mendelian randomisation analysis involving the following methods: MR-Egger, weighted median, inverse variance weighted, simple mode, and weighted mode. RESULTS: This study demonstrated a lack of empirical substantiation for a causal association between genetic variants in MN and the susceptibility to lung, colon, prostate, or breast cancer. CONCLUSION: Overall, we did not detect a causal link between MN and lung, colon, breast, or prostate cancer. Hence, additional research is imperative to elucidate the underlying factors contributing to the heightened occurrence of tumour in patients with MN.
Assuntos
Predisposição Genética para Doença , Glomerulonefrite Membranosa , Análise da Randomização Mendeliana , Neoplasias da Próstata , Glomerulonefrite Membranosa/genética , Humanos , Masculino , Neoplasias da Próstata/genética , Feminino , Neoplasias/genética , Neoplasias da Mama/genética , Neoplasias do Colo/genética , Neoplasias Pulmonares/genéticaRESUMO
Benign prostatic hyperplasia (BPH), commonly seen in older men, can cause symptoms of discomfort, and may even need surgical intervention. Studies have shown the potential link between gut microbes and BPH, but the molecular association is not fully understood. METHODS: Four-week-old male Sprague-Dawley rats (n = 16) were randomly allocated to normal control diet (ND, 10% fat) and high-fat diet-induced BPH (HFD, 45% fat) groups. Metagenomic analysis was used to examine the abundance and discrepancies in gut microbiota within the two groups after 24 weeks of feeding. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis was conducted to assess the biological functions of the differentially expressed genes. RESULTS: Rats with HFD-induced obesity exhibited morphological abnormalities in their prostate tissues. Metagenomic analysis of the gut revealed that Firmicutes were the dominant phyla in the HFD group, whereas the ND group had a higher abundance of Spirochaetes. At the genus level, Ruminococcus spp exhibited greater abundance in the HFD group, whereas Treponema spp were more abundant in the ND group. KEGG analysis demonstrated that the differentially expressed genes were mainly enriched in the NOD-like receptor (NLR) signaling, PI3K-Akt signaling, estrogen-signaling, signalings associated with GABAergic synapses, pantothenate and CoA biosynthesis. CONCLUSION: The findings of our study indicated that there was a notable variation in the microbiota abundance within the intestinal tract of obese rats suffering from prostate hyperplasia. It is plausible that these differentially abundant bacteria played a role in the development of pathological alterations in the prostate through the facilitation of inflammatory responses; however, additional research is required to validate the findings.
RESUMO
Exercise has proven cardiac benefits, but the underlying mechanisms of exercise that protect the heart from acute sympathetic stress injuries remain unknown. In this study, adult C57BL/6J mice and their AMP-activated protein kinase α2 knockout (AMPKα2-/-) littermates were either subjected to 6 weeks of exercise training or housed under sedentary conditions and then treated with or without a single subcutaneous injection of the ß-adrenergic receptor (ß-AR) agonist isoprenaline (ISO). We investigated the differences in the protective effects of exercise training on ISO-induced cardiac inflammation in wild-type (WT) and AMPKα2-/- mice using histology, enzyme-linked immunosorbent assay (ELISA) and Western blotting analyses. The results indicated that exercise training alleviated ISO-induced cardiac macrophage infiltration, chemokines and the expression of proinflammatory cytokines in wild-type mice. A mechanism study showed that exercise training attenuated the ISO-induced production of reactive oxygen species (ROS) and the activation of NLR Family, pyrin domain-containing 3 (NLRP3) inflammasomes. In cardiomyocytes, the ISO-induced effects on these processes were inhibited by AMP-activated protein kinase (AMPK) activator (metformin) pretreatment and reversed by the AMPK inhibitor (compound C). AMPKα2-/- mice showed more extensive cardiac inflammation following ISO exposure than their wild-type littermates. These results indicated that exercise training could attenuate ISO-induced cardiac inflammation by inhibiting the ROS-NLRP3 inflammasome pathway in an AMPK-dependent manner. Our findings suggested the identification of a novel mechanism for the cardioprotective effects of exercise.
Assuntos
Proteínas Quinases Ativadas por AMP , Receptores Adrenérgicos beta , Camundongos , Animais , Proteínas Quinases Ativadas por AMP/genética , Proteínas Quinases Ativadas por AMP/metabolismo , Receptores Adrenérgicos beta/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/genética , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Camundongos Endogâmicos C57BL , Inflamassomos/metabolismo , Isoproterenol/toxicidade , Arritmias Cardíacas , Agonistas Adrenérgicos beta/toxicidade , Miócitos Cardíacos/metabolismo , Exercício Físico , Inflamação/metabolismoRESUMO
During acute sympathetic stress, the overactivation of ß-adrenergic receptors (ß-ARs) causes cardiac fibrosis by triggering inflammation and cytokine expression. It is unknown whether exercise training inhibits acute ß-AR overactivation-induced cytokine expression and cardiac injury. Here, we report that running exercise inhibited cardiac fibrosis and improved cardiac function in mice treated with isoproterenol (ISO), a ß-AR agonist. A cytokine antibody array revealed that running exercise prevented most of the changes in cytokine expression induced by ISO. Specifically, ISO-induced upregulation of 18 cytokines was prevented by running exercise. A Kyoto encyclopedia of genes and genomes analysis of these cytokines revealed that Hedgehog and RAP1 signaling pathways were involved in the regulation of cytokine expression by exercise. The changes in the expression of some cytokines that were prevented by exercise were verified by an enzyme-linked immunosorbent assay and real-time PCR. In conclusion, running exercise prevented the cytokine expression changes after acute ß-AR overactivation and therefore attenuated cardiac fibrosis. Acute sympathetic stress is an important risk factor for the patients with cardiovascular diseases, and the present study revealed that exercise training can prevent against the upregulation of cytokines and the subsequent cardiac injury induced by acute sympathetic stress, suggesting that exercise training may be beneficial for cardiovascular patients who are in risk of acute sympathetic stress. This finding provides a theoretical basis for the application of exercise training in patients who may suffer from acute sympathetic stress.