CCl4-induced hepatic injury in mice fed a Western diet is associated with blunted healing.
OBJECTIVE
Feeding a Western diet (WD) enriched in saturated fat protects against chronic alcoholic hepatitis. However, saturated fat induces lipotoxicity in cultured hepatocytes. The purpose of the present study was to elucidate the influence of WD on acute hepatic injury and healing.


METHODS
Male C57BL/6 mice were fed a purified control diet (CD) or WD enriched in palmitate and cholesterol. After 3 weeks, carbon tetrachloride (CCl(4)) was administered (0.1 microL/g, intraperitoneally). Hepatic inflammation and proliferation were assessed by immunostaining for neutrophils and intracellular adhesion molecule-1, and Ki67, respectively. Cytokine expression was analyzed by real-time polymerase chain reaction. Protein levels of peroxisome proliferator-activated receptor-gamma (PPAR-gamma) were assessed by western blotting.


RESULTS
Feeding a WD resulted in markedly greater histological evidence of necrosis and enhanced alanine aminotransferase activity (188 +/- 6.2 U/L) compared to CD-fed mice (99.1 +/- 6.3 U/L) by day 2 post-CCl(4). In contrast, WD blunted leukocyte accumulation in necrotic areas and the expression of cytokines (tumor necrosis factor-alpha and interleukin-6) involved in tissue regeneration. Diminished repair was further indexed by lower collagen-alphaI and Ki67 expression in the mice fed a WD. Finally, feeding a WD, as well as the treatment of cultured hepatocytes with palmitic acid, upregulated the expression of PPAR-gamma, which has been previously shown to prevent hepatic repair following CCl(4) exposure.


CONCLUSIONS
These findings suggest that impaired healing in WD-fed mice blunted recovery from acute injury and underscored the complex relationship between diet and hepatic injury.
Allman
Monique
M
Department of Molecular and Cellular Physiology, Louisiana State University Health Sciences Center, Shreveport, Louisiana 71130, USA.
Gaskin
Latausha
L
Rivera
Chantal A
CA
D000410:Alanine Transaminase / Q000378:metabolism; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D015153:Blotting, Western; D002251:Carbon Tetrachloride; D056486:Chemical and Drug Induced Liver Injury / Q000150:complications; D024042:Collagen Type I / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D004032:Diet; D004195:Disease Models, Animal; D005227:Fatty Acids / Q000008:administration & dosage / Q000009:adverse effects*; D007249:Inflammation / Q000378:metabolism; D007274:Injections, Intraperitoneal; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D019394:Ki-67 Antigen / Q000378:metabolism; D008107:Liver Diseases / Q000235:genetics / Q000378:metabolism* / Q000473:pathology / Q000517:prevention & control*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009336:Necrosis / Q000139:chemically induced; D009504:Neutrophils / Q000378:metabolism; D047495:PPAR gamma / Q000378:metabolism; D016133:Polymerase Chain Reaction
D015415:Biomarkers; D024042:Collagen Type I; D016207:Cytokines; D005227:Fatty Acids; D019394:Ki-67 Antigen; D047495:PPAR gamma; D018799:Intercellular Adhesion Molecule-1; D002251:Carbon Tetrachloride; D000410:Alanine Transaminase