Effects of Dietary Different Doses of Copper and High Fructose Feeding on Rat Fecal Metabolome

Abstract

The gut microbiota plays a critical role in the pathogenesis of nonalcoholic fatty liver disease (NAFLD). Increased fructose consumption and inadequate copper intake are two critical risk factors in the development of NAFLD. To gain insight into the role of gut microbiota, fecal metabolites, obtained from rats exposed to different dietary levels of copper with and without high fructose intake for 4 weeks, were analyzed by comprehensive two-dimensional gas chromatography time-of-flight mass spectrometry (GC × GC-TOF MS). In parallel, liver tissues were assessed by histology and triglyceride assay. Our data showed that high fructose feeding led to obvious hepatic steatosis in both marginal copper deficient rats and copper supplementation rats. Among the 38 metabolites detected with significant abundance alteration between groups, short chain fatty acids were markedly decreased with excessive fructose intake irrespective of copper levels. C15:0 and C17:0 long chain fatty acids, produced only by bacteria, were increased by either high copper level or high fructose intake. In addition, increased fecal urea and malic acid paralleled the increased hepatic fat accumulation. Collectively, GC × GC-TOF MS analysis of rat fecal samples revealed distinct fecal metabolome profiles associated with the dietary high fructose and copper level, with some metabolites possibly serving as potential noninvasive biomarkers of fructose induced-NAFLD.

Melatonin regulates the neurotransmitter secretion disorder induced by caffeine through the gut-brain axis in zebrafish (Danio rerio)

“…The concentrations of dopamine (DA), γ-aminobutyric acid (γ-GABA) and 5-hydroxytryptamine (5-HT) in head tissue were calculated based on the optical absorbance value at 450 nm (OD450) determined by a microplate reader. The fatty acid concentrations in zebrafish intestines were quantified by a gas chromatography-mass spectrometry (GC-MS) assay [43] . An Agilent 7890B gas chromatograph equipped with a mass spectrometer (Agilent 5977A, Agilent, Santa Clara, CA, USA) was used to conduct the analysis of the samples, and an HP-5 MS column (30 m x 0.25 mm, 0.25 μm, Agilent, Santa Clara, CA, USA) was employed to achieve separation.…”

Fructose: A Dietary Sugar in Crosstalk with Microbiota Contributing to the Development and Progression of Non-Alcoholic Liver Disease

“…In addition, the microbiota itself was shown to contribute to the progression of liver disease and injury and diet-induced NAFLD resulted in dysbiosis and a strong decrease in microbial diversity ( 66 ). Although the underlying mechanisms are not fully discovered yet, fructose is known to be highly involved in the development of NAFLD by altering gut metabolites ( 52 , 60 ). Fructose increased the intestinal translocation of endotoxins and endotoxin levels in plasma ( 49 , 64 ) contributing to inflammation and degrading of the mucosa barrier.…”

Sex Differences in Dietary Copper-Fructose Interaction-Induced Alterations of Gut Microbial Activity are Not Correlated to Hepatic Steatosis

“…Previous studies have shown that distinct alterations of the gut microbiome are linked to speci c metabolic traits (38) as well as to different stages of NAFLD (39,40), leading to the hypothesis that sex differences in the gut microbiota is linked to distinct metabolic phenotypes or disease severity. Our previous studies have shown that dietary copper-fructose interactions shifted gut microbiota and correlated to the development of hepatic steatosis in male rats (41,42). Given that diet shapes the gut microbiome in a sex-speci c manner (36), we aimed to determine whether dietary copper-fructose interaction alters gut microbiota and induces hepatic steatosis in a sex-dependent manner and whether sex differences in metabolic phenotype contribute to the distinct alterations of the gut microbiota.…”