title: Combination of alcohol and fructose exacerbates metabolic imbalance in terms of hepatic damage, dyslipidemia, and insulin resistance in rats.
abstract: Although both alcohol and fructose are particularly steatogenic, their long-term effect in the development of a metabolic syndrome has not been studied in vivo. Consumption of fructose generally leads to obesity, whereas ethanol can induce liver damage in the absence of overweight. Here, Sprague-Dawley rats were fed ad libitum for 28 days on five diets: chow (control), liquid Lieber-DeCarli (LDC) diet, LDC +30%J of ethanol (L-Et) or fructose (L-Fr), and LDC combined with 30%J ethanol and 30%J fructose (L-EF). Body weight (BW) and liver weight (LW) were measured. Blood and liver samples were harvested and subjected to biochemical tests, histopathological examinations, and RT-PCR. Alcohol-containing diets substantially reduced the food intake and BW (≤3rd week), whereas fructose-fed animals had higher LW than controls (P<0.05). Additionally, leukocytes, plasma AST and leptin levels were the highest in the fructose-administered rats. Compared to the chow and LDC diets, the L-EF diet significantly elevated blood glucose, insulin, and total-cholesterol levels (also vs. the L-Et group). The albumin and Quick-test levels were the lowest, whereas ALT activity was the highest in the L-EF group. Moreover, the L-EF diet aggravated plasma triglyceride and reduced HDL-cholesterol levels more than 2.7-fold compared to the sum of the effects of the L-Et and L-Fr diets. The decreased hepatic insulin clearance in the L-EF group vs. control and LDC groups was reflected by a significantly decreased C-peptide:insulin ratio. All diets except the control caused hepatosteatosis, as evidenced by Nile red and H&E staining. Hepatic transcription of insulin receptor substrate-1/2 was mainly suppressed by the L-Fr and L-EF diets. The L-EF diet did not enhance the mitochondrial β-oxidation of fatty acids (Cpt1α and Ppar-α expressions) compared to the L-Et or L-Fr diet. Together, our data provide evidence for the coaction of ethanol and fructose with a high-fat-diet on dyslipidemia and insulin resistance-accompanied liver damage.
authors.affiliation: Department Gastroenterology and Endocrinology, University Medical Center Goettingen, Goettingen, Germany.
authors.forename: Salamah Mohammad
authors.initials: SM
authors.lastname: Alwahsh
authors.affiliation: Department of General, Visceral, and Pediatric Surgery, University Medical Center Goettingen, Goettingen, Germany.
authors.forename: Min
authors.initials: M
authors.lastname: Xu
authors.affiliation: Department Gastroenterology and Endocrinology, University Medical Center Goettingen, Goettingen, Germany.
authors.forename: Frank Christian
authors.initials: FC
authors.lastname: Schultze
authors.affiliation: Institute of Anatomy and Cell Biology, University Medical Center Goettingen, Goettingen, Germany.
authors.forename: Jörg
authors.initials: J
authors.lastname: Wilting
authors.affiliation: Department Gastroenterology and Endocrinology, University Medical Center Goettingen, Goettingen, Germany.
authors.forename: Sabine
authors.initials: S
authors.lastname: Mihm
authors.affiliation: Department Gastroenterology and Endocrinology, University Medical Center Goettingen, Goettingen, Germany.
authors.forename: Dirk
authors.initials: D
authors.lastname: Raddatz
authors.affiliation: Department Gastroenterology and Endocrinology, University Medical Center Goettingen, Goettingen, Germany.
authors.forename: Giuliano
authors.initials: G
authors.lastname: Ramadori
mesh_terms: D000818:Animals; D008076:Cholesterol, HDL / Q000097:blood; D050171:Dyslipidemias / Q000097:blood / Q000139:chemically induced / Q000473:pathology; D000431:Ethanol / Q000009:adverse effects* / Q000494:pharmacology; D005632:Fructose / Q000009:adverse effects* / Q000494:pharmacology; D007333:Insulin Resistance; D008099:Liver / Q000293:injuries / Q000378:metabolism / Q000473:pathology; D008297:Male; D024821:Metabolic Syndrome / Q000097:blood / Q000139:chemically induced / Q000473:pathology; D008930:Mitochondria, Liver / Q000378:metabolism / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D014280:Triglycerides / Q000097:blood
chemical_list: D008076:Cholesterol, HDL; D014280:Triglycerides; D005632:Fructose; D000431:Ethanol
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