Analysis of sex differences in dietary copper-fructose interaction-induced alterations of gut microbial activity in relation to hepatic steatosis
Year: 2021
Type: article
Abstract: BACKGROUND: Inadequate copper intake and increased fructose consumption represent two important nutritional problems in the USA. Dietary copper-fructose interactions alter gut microbial activity and contribute to the development of nonalcoholic fatty liver disease (NAFLD). The aim of this study is to determine whether dietary copper-fructose interactions alter gut microbial activity in a sex-differential manner and whether sex differences in gut microbial activity are associated with sex differences in hepatic steatosis. METHODS: Male and female weanling Sprague-Dawley (SD) rats were fed ad libitum with an AIN-93G purified rodent diet with defined copper content for 8 weeks. The copper content is 6 mg/kg and 1.5 mg/kg in adequate copper diet (CuA) and marginal copper diet (CuM), respectively. Animals had free access to either deionized water or deionized water containing 10% fructose (F) (w/v) as the only drink during the experiment. Body weight, calorie intake, plasma alanine aminotransferase, aspartate aminotransferase, and liver histology as well as liver triglyceride were evaluated. Fecal microbial contents were analyzed by 16S ribosomal RNA (16S rRNA) sequencing. Fecal and cecal short-chain fatty acids (SCFAs) were determined by gas chromatography-mass spectrometry (GC-MS). RESULTS: Male and female rats exhibit similar trends of changes in the body weight gain and calorie intake in response to dietary copper and fructose, with a generally higher level in male rats. Several female rats in the CuAF group developed mild steatosis, while no obvious steatosis was observed in male rats fed with CuAF or CuMF diets. Fecal 16S rRNA sequencing analysis revealed distinct alterations of the gut microbiome in male and female rats. Linear discriminant analysis (LDA) effect size (LEfSe) identified sex-specific abundant taxa in different groups. Further, total SCFAs, as well as, butyrate were decreased in a more pronounced manner in female CuMF rats than in male rats. Of note, the decreased SCFAs are concomitant with the reduced SCFA producers, but not correlated to hepatic steatosis. CONCLUSIONS: Our data demonstrated sex differences in the alterations of gut microbial abundance, activities, and hepatic steatosis in response to dietary copper-fructose interaction in rats. The correlation between sex differences in metabolic phenotypes and alterations of gut microbial activities remains elusive.
Source: Biology of Sex Differences
Language: English
Topic: Gut microbiota and health
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $2,690
Funders: U.S. Department of Veterans Affairs, James Graham Brown Foundation, University of Louisville, National Institutes of Health, Office of Academic Affiliations, Department of Veterans Affairs, National Institute on Alcohol Abuse and Alcoholism, National Institute of General Medical Sciences, National Institute of Allergy and Infectious Diseases, National Institute of Diabetes and Digestive and Kidney Diseases, National Institute of Environmental Health Sciences
Awards: G1354351666, G1486559928, G1578363164, Gut extracellular vesicles promote alcohol-induced liver injury via TLR4-regulated miRNAs, Molecular Targets Phase III CoBRE, Intestinal epithelial cells-derived exosomal miRNAs regulate liver inflammation in obesity, G3072387838, G3198037347, G3657198001, G4351898368, CSN8 regulation of S1P-enriched extracellular vesicles to modulate NAFLD by gut-liver axis, G5260253374, G6290778202, G7660573574, G7834131122, G8942210600, G9000013980, G9000091663, G9000129888, The Role of Nutrition in the Development/Progression of Alcohol-Induced Organ Injury, Summer Environmental Health Sciences Training Program, Hepatobiology and Toxicology COBRE, IDeA Networks of Biomedical Research Excellence in Kentucky, Integrated therapies for alcohol use and ALD (ITAALD) Network -UofL Clinical Center
OpenAlex ID: W3118423163