Subchronic Exposure of Mice to Cadmium Perturbs Their Hepatic Energy Metabolism and Gut Microbiome.
Cadmium (Cd) is an environmental pollutant known to cause liver damage; however, the mechanisms of its hepatotoxicity remain poorly understood. In this study, the effects of subchronic exposure in mice to low doses of Cd on energy metabolism and the gut microbiome were evaluated. The exposure of mice to 10 mg/L Cd supplied in drinking water for 10 weeks increased hepatic triacylglycerol (TG), serum free fatty acid (FFA), and TG levels. The mRNA levels of several key genes involved in both de novo FFA synthesis and transport pathways and in TG synthesis in the liver also increased significantly in the Cd-treated mice, indicating that alterations of these genes may be a possible mechanism to explain subchronic Cd exposure induced hepatic toxicity at a molecular level. As for the gut microbiome, at the phylum level, the amounts of Firmicutes and γ-proteobacteria decreased significantly in the feces after 4 weeks of Cd exposure, and the quantity of Firmicutes decreased significantly in the cecum contents after 10 weeks of Cd exposure. In addition, 16S rRNA gene sequencing further revealed that Cd exposure significantly perturbed the gut microflora structure and richness at family and genus levels. The alteration of gut microbiome composition might result in an increase in serum lipopolysaccharide (LPS) and induce hepatic inflammation, which may indirectly cause perturbations of energy homeostasis after Cd exposure. Taken together, the present study indicated that subchronic Cd exposure caused the dysregulation of energy metabolism and changed the gut microbiome composition in mice.
College of Biological and Environmental Engineering, Zhejiang University of Technology , Hangzhou 310032, China.
Songbin
S
Zhang
College of Biological and Environmental Engineering, Zhejiang University of Technology , Hangzhou 310032, China.
Yuanxiang
Y
Jin
College of Biological and Environmental Engineering, Zhejiang University of Technology , Hangzhou 310032, China.
Zhaoyang
Z
Zeng
College of Biological and Environmental Engineering, Zhejiang University of Technology , Hangzhou 310032, China.
Zhenzhen
Z
Liu
College of Biological and Environmental Engineering, Zhejiang University of Technology , Hangzhou 310032, China.
Zhengwei
Z
Fu
D000818:Animals; D002104:Cadmium / Q000032:analysis / Q000633:toxicity*; D004734:Energy Metabolism / Q000187:drug effects*; D004785:Environmental Pollutants / Q000633:toxicity*; D005228:Fatty Acids, Essential / Q000097:blood; D005243:Feces / Q000737:chemistry / Q000382:microbiology; D000068536:Bacillota / Q000235:genetics / Q000302:isolation & purification; D020563:Gammaproteobacteria / Q000235:genetics / Q000302:isolation & purification; D000069196:Gastrointestinal Microbiome / Q000187:drug effects*; D050356:Lipid Metabolism / Q000235:genetics; D008070:Lipopolysaccharides / Q000097:blood / Q000633:toxicity; D008099:Liver / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D012336:RNA, Ribosomal, 16S / Q000737:chemistry / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D017423:Sequence Analysis, RNA; D014158:Transcription, Genetic / Q000187:drug effects; D014280:Triglycerides / Q000032:analysis / Q000097:blood
D004785:Environmental Pollutants; D005228:Fatty Acids, Essential; D008070:Lipopolysaccharides; D012336:RNA, Ribosomal, 16S; D014280:Triglycerides; D002104:Cadmium