Highlights d High-alcohol-producing strains of Klebsiella pneumoniae exist in humans d HiAlc Kpn is associated with NAFLD in a human cohort d Transplant of HiAlc Kpn into mice causes NAFLD d Feeding mice glucose led to detectable blood alcohol, suggesting a biomarker for NAFLD
BackgroundAssessment and characterization of human colon microbiota is now a major research area in human diseases, including in patients with hepatitis B liver cirrhosis (HBLC).MethodsWe recruited 120 patients with HBLC and 120 healthy controls. The fecal microbial community and functions in the two groups were analyzed using high-throughput Solexa sequencing of the complete metagenomic DNA and bioinformatics methods.ResultsCommunity and metabolism-wide changes of the fecal microbiota in 20 HBLC patients and 20 healthy controls were observed and compared. A negative correlation was observed between the Child-Turcotte-Pugh scores and Bacteroidetes (P < 0.01), whereas a positive correlation was observed between the scores and Enterobacteriaceae and Veillonella (P < 0.01). Analysis of the additional 200 fecal microbiota samples demonstrated that these intestinal microbial markers might be useful for distinguishing liver cirrhosis microbiota samples from normal ones. The functional diversity was significantly reduced in the fecal microbiota of cirrhotic patients compared with in the controls. At the module or pathway levels, the fecal microbiota of the HBLC patients showed enrichment in the metabolism of glutathione, gluconeogenesis, branched-chain amino acid, nitrogen, and lipid (P < 0.05), whereas there was a decrease in the level of aromatic amino acid, bile acid and cell cycle related metabolism (P < 0.05).ConclusionsExtensive differences in the microbiota community and metabolic potential were detected in the fecal microbiota of cirrhotic patients. The intestinal microbial community may act as an independent organ to regulate the body’s metabolic balance, which may affect the prognosis for HBLC patients.
High sodium intake is a major risk factor for developing hypertension in diabetes. Promotion of sodium excretion reduces cardiometabolic lesions in diabetes. However, the interaction between sodium intake and glucose homeostasis remains elusive. Here, we report that high sodium intake remarkably increased natriuresis in wild-type mice, but this effect was blunted in adipose-specific PPARδ knockout mice and diabetic mice. PPARδ activation in perirenal fat by agonist or high sodium intake inhibited renal sodium-glucose cotransporter 2 (SGLT2) function, which is mediated by increased production of adipose adiponectin. In addition, high salt intake-induced natriuresis was impaired in diabetic states because of renal SGLT2 dysfunction. Type 2 diabetic patients with uncontrolled hyperglycemia had less natriuresis that was correlated to their plasma adiponectin levels. Our findings provide insights into the distinctive role of the PPARδ/adiponectin/SGLT2 pathway in the regulation of sodium and glucose homeostasis.
The whitening and loss of brown adipose tissue (BAT) during obesity and aging promote metabolic disorders and related diseases. The imbalance of Ca2+ homeostasis accounts for the dysfunction and clearance of mitochondria during BAT whitening. Capsaicin, a dietary factor activating TRPV1, can inhibit obesity induced by high-fat diet (HFD), but whether capsaicin inhibits BAT loss and the underlying mechanism remain unclear. In this study, we determined that the inhibitory effects of capsaicin on HFD-induced obesity and BAT whitening were dependent on the participation of SIRT3, a critical mitochondrial deacetylase. SIRT3 also mediated all of the beneficial effects of capsaicin on alleviating reactive oxygen species generation, elevating mitochondrial activity, and restricting mitochondrial calcium overload induced by HFD. Mechanistically, SIRT3 inhibits mitochondrial calcium uniporter (MCU)-mediated mitochondrial calcium overload by reducing the H3K27ac level on the MCU promoter in an AMPK-dependent manner. In addition, HFD also inhibits AMPK activity to reduce SIRT3 expression, which could be reversed by capsaicin. Capsaicin intervention also inhibited aging-induced BAT whitening through this mechanism. In conclusion, this study emphasizes a critical role of the AMPK/SIRT3 pathway in the maintenance of BAT morphology and function and suggests that intervention in this pathway may be an effective target for preventing obesity- or age-related metabolic diseases.
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