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High fat diet feeding exaggerates perfluorooctanoic acid-induced liver injury in mice via modulating multiple metabolic pathways
- Source :
- PLoS ONE, PLoS ONE, Vol 8, Iss 4, p e61409 (2013)
- Publication Year :
- 2012
-
Abstract
- High fat diet (HFD) is closely linked to a variety of health issues including fatty liver. Exposure to perfluorooctanoic acid (PFOA), a synthetic perfluorinated carboxylic acid, also causes liver injury. The present study investigated the possible interactions between high fat diet and PFOA in induction of liver injury. Mice were pair-fed a high-fat diet (HFD) or low fat control with or without PFOA administration at 5 mg/kg/day for 3 weeks. Exposure to PFOA alone caused elevated plasma alanine aminotransferase (ALT) and alkaline phosphatase (ALP) levels and increased liver weight along with reduced body weight and adipose tissue mass. HFD alone did not cause liver damage, but exaggerated PFOA-induced hepatotoxicity as indicated by higher plasma ALT and AST levels, and more severe pathological changes including hepatocyte hypertrophy, lipid droplet accumulation and necrosis as well as inflammatory cell infiltration. These additive effects of HFD on PFOA-induced hepatotoxicity correlated with metabolic disturbance in liver and blood as well as up-regulation of hepatic proinflammatory cytokine genes. Metabolomic analysis demonstrated that both serum and hepatic metabolite profiles of PFOA, HFD, or HFD-PFOA group were clearly differentiated from that of controls. PFOA affected more hepatic metabolites than HFD, but HFD showed positive interaction with PFOA on fatty acid metabolites including long chain fatty acids and acylcarnitines. Taken together, dietary high fat potentiates PFOA-induced hepatic lipid accumulation, inflammation and necrotic cell death by disturbing hepatic metabolism and inducing inflammation. This study demonstrated, for the first time, that HFD increases the risk of PFOA in induction of hepatotoxicity.
- Subjects :
- Male
Adipose tissue
Toxicology
chemistry.chemical_compound
Mice
chemistry.chemical_classification
Liver injury
Fluorocarbons
Multidisciplinary
biology
Liver Diseases
Fatty liver
Fatty Acids
Alanine Transaminase
Organ Size
medicine.anatomical_structure
Liver
Hepatocyte
Perfluorooctanoic acid
Medicine
Public Health
Caprylates
Environmental Health
Research Article
medicine.medical_specialty
Science
Adipose Tissue, White
Toxic Agents
Predictive Toxicology
Gastroenterology and Hepatology
Diet, High-Fat
Necrosis
Internal medicine
medicine
Animals
Aspartate Aminotransferases
Biology
Triglycerides
Nutrition
Inflammation
Gene Expression Profiling
Body Weight
Fatty acid
Lipid metabolism
medicine.disease
Lipid Metabolism
Fatty Liver
Mice, Inbred C57BL
Endocrinology
chemistry
Alanine transaminase
Gene Expression Regulation
Metabolic Disorders
biology.protein
Hepatocytes
Subjects
Details
- ISSN :
- 19326203
- Volume :
- 8
- Issue :
- 4
- Database :
- OpenAIRE
- Journal :
- PloS one
- Accession number :
- edsair.doi.dedup.....679fe2616257c3060058941a140f636f