Dietary fructose augments ethanol-induced liver pathology.
Certain dietary components when combined with alcohol exacerbate alcohol-induced liver injury (ALI). Here, we tested whether fructose, a major ingredient of the western diet, enhances the severity of ALI. We fed mice ethanol for 8 weeks in the following Lieber-DeCarli diets: (a) Regular (contains olive oil); (b) corn oil (contains corn oil); (c) fructose (contains fructose and olive oil) and (d) corn+fructose (contains fructose and corn oil). We compared indices of metabolic function and liver pathology among the different groups. Mice fed fructose-free and fructose-containing ethanol diets exhibited similar levels of blood alcohol, blood glucose and signs of disrupted hepatic insulin signaling. However, only mice given fructose-ethanol diets showed lower insulin levels than their respective controls. Compared with their respective pair-fed controls, all ethanol-fed mice exhibited elevated levels of serum ALT; the inflammatory cytokines TNF-α, MCP-1 and MIP-2; hepatic lipid peroxides and triglycerides. All the latter parameters were significantly higher in mice given fructose-ethanol diets than those fed fructose-free ethanol diets. Mice given fructose-free or fructose-containing ethanol diets each had higher levels of hepatic lipogenic enzymes than controls. However, the level of the lipogenic enzyme fatty acid synthase (FAS) was significantly higher in livers of mice given fructose control and fructose-ethanol diets than in all other groups. Our findings indicate that dietary fructose exacerbates ethanol-induced steatosis, oxidant stress, inflammation and liver injury, irrespective of the dietary fat source, to suggest that inclusion of fructose in or along with alcoholic beverages increases the risk of more severe ALI in heavy drinkers.
Department of Internal Medicine, Carolinas Medical Center, Charlotte, NC, USA. Electronic address: Paul.Thomes@Carolinashealthcare.org.
Paul G
PG
Thomes
Department of Internal Medicine, Carolinas Medical Center, Charlotte, NC, USA.
Jennifer H
JH
Benbow
Department of Internal Medicine, Carolinas Medical Center, Charlotte, NC, USA.
Elizabeth
E
Brandon-Warner
Department of Surgery, Carolinas Medical Center.
Kyle J
KJ
Thompson
Department of Pathology, Carolinas Medical Center.
Carl
C
Jacobs
Departments of Internal Medicine and Biochemistry/Molecular Biology, University of Nebraska Medical Center, Omaha, NE, USA.
Terrence M
TM
Donohue
Department of Internal Medicine, Carolinas Medical Center, Charlotte, NC, USA. Electronic address: Laura.Schrum@Carolinashealthcare.org.
Laura W
LW
Schrum
D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D001343:Autophagy / Q000187:drug effects; D015415:Biomarkers / Q000378:metabolism; D056486:Chemical and Drug Induced Liver Injury / Q000378:metabolism / Q000473:pathology; D019392:Cytochrome P-450 CYP2E1 / Q000378:metabolism; D004041:Dietary Fats / Q000494:pharmacology; D000431:Ethanol / Q000009:adverse effects*; D005632:Fructose / Q000009:adverse effects*; D008658:Inactivation, Metabolic; D008099:Liver / Q000187:drug effects* / Q000473:pathology*; D008297:Male; D008810:Mice, Inbred C57BL; D013230:Stearoyl-CoA Desaturase / Q000378:metabolism; D019014:fas Receptor / Q000378:metabolism
D015415:Biomarkers; D004041:Dietary Fats; C491899:Fas protein, mouse; D019014:fas Receptor; D005632:Fructose; D000431:Ethanol; D019392:Cytochrome P-450 CYP2E1; C490333:Scd1 protein, mouse; D013230:Stearoyl-CoA Desaturase; D000410:Alanine Transaminase
Alcohol; Fatty liver; Fructose; Inflammation; Insulin; Oxidant stress