Proteomic analysis of fructose-induced fatty liver in hamsters.
High fructose consumption is associated with the development of fatty liver and dyslipidemia with poorly understood mechanisms. We used a matrix-assisted laser desorption/ionization-based proteomics approach to define the molecular events that link high fructose consumption to fatty liver in hamsters. Hamsters fed high-fructose diet for 8 weeks, as opposed to regular-chow-fed controls, developed hyperinsulinemia and hyperlipidemia. High-fructose-fed hamsters exhibited fat accumulation in liver. Hamsters were killed, and liver tissues were subjected to matrix-assisted laser desorption/ionization-based proteomics. This approach identified a number of proteins whose expression levels were altered by >2-fold in response to high fructose feeding. These proteins fall into 5 different categories including (1) functions in fatty acid metabolism such as fatty acid binding protein and carbamoyl-phosphate synthase; (2) proteins in cholesterol and triglyceride metabolism such as apolipoprotein A-1 and protein disulfide isomerase; (3) molecular chaperones such as GroEL, peroxiredoxin 2, and heat shock protein 70, whose functions are important for protein folding and antioxidation; (4) enzymes in fructose catabolism such as fructose-1,6-bisphosphatase and glycerol kinase; and (5) proteins with housekeeping functions such as albumin. These data provide insight into the molecular basis linking fructose-induced metabolic shift to the development of metabolic syndrome characterized by hepatic steatosis and dyslipidemia.
Zhang
Lihe
L
Division of Immunogenetics, Department of Pediatrics, Children's Hospital of Pittsburgh, University of Pittsburgh School of Medicine, Rangos Research Center, Pittsburgh, PA 15213, USA.
Perdomo
German
G
Kim
Dae Hyun
DH
Qu
Shen
S
Ringquist
Steven
S
Trucco
Massimo
M
Dong
H Henry
HH
D000818:Animals; D016632:Apolipoprotein A-I / Q000378:metabolism; D002222:Carbamoyl-Phosphate Synthase (Ammonia) / Q000378:metabolism; D018834:Chaperonin 60 / Q000378:metabolism; D006224:Cricetinae; D004040:Dietary Carbohydrates / Q000008:administration & dosage* / Q000378:metabolism; D050556:Fatty Acid-Binding Proteins / Q000378:metabolism; D005234:Fatty Liver / Q000097:blood / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D005632:Fructose / Q000008:administration & dosage* / Q000378:metabolism; D006597:Fructose-Bisphosphatase / Q000378:metabolism; D005951:Glucose Tolerance Test; D005991:Glycerol Kinase / Q000378:metabolism; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism; D006651:Histocytochemistry; D006946:Hyperinsulinism / Q000139:chemically induced / Q000378:metabolism; D006949:Hyperlipidemias / Q000139:chemically induced / Q000378:metabolism; D008297:Male; D008647:Mesocricetus; D054464:Peroxiredoxins / Q000378:metabolism; D019704:Protein Disulfide-Isomerases / Q000378:metabolism; D040901:Proteomics / Q000379:methods*; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization / Q000379:methods
D016632:Apolipoprotein A-I; D018834:Chaperonin 60; D004040:Dietary Carbohydrates; D050556:Fatty Acid-Binding Proteins; D018840:HSP70 Heat-Shock Proteins; D005632:Fructose; D054464:Peroxiredoxins; D005991:Glycerol Kinase; D006597:Fructose-Bisphosphatase; D019704:Protein Disulfide-Isomerases; D002222:Carbamoyl-Phosphate Synthase (Ammonia)