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Title: A diet rich in OMEGA-6 polyunsaturated fat and sucrose reproduces key features of metabolic syndrome in C57BL/6 mice

Author
item HIMES, RYAN - Baylor College Of Medicine
item COPE-YOKOYAMA, S - University Of Texas Southwestern Medical Center
item SMITH, C - Children'S Nutrition Research Center (CNRC)

Submitted to: Journal of Pediatric Gastroenterology and Nutrition
Publication Type: Abstract Only
Publication Acceptance Date: 5/1/2009
Publication Date: 5/1/2009
Citation: Himes, R.W., Cope-Yokoyama, S.D., Smith, C.W. 2009. A diet rich in OMEGA-6 polyunsaturate fat and sucrose reproduces key features of metabolic syndrome in C57BL/6 mice. Journal of Pediatric Gastroenterology and Nutrition. 48(Suppl.3): E128.

Interpretive Summary:

Technical Abstract: To determine whether a diet enriched in v-6 fatty acids and sucrose will reproduce features of metabolic syndrome in C57BL/6 mice. 4- to 7-week-old male C57BL/6 mice were randomized to chow (13% kcal fat, lard and corn oil) or high fat/high sucrose (HF/HS) diet (48% kcal fat, corn oil) for a period of 4–6 weeks. Food consumption was monitored and weekly weights were obtained. Fasting blood samples were obtained at sacrifice for serum insulin, glucose, cholesterol and alanine aminotransferase(ALT). Portions of the liver were allocated for routine histology, oil-red-o staining and gene expression analysis by quantitative real-time PCR. Diet intake was isocaloric between groups however; HF/HS mice had significantly greater weight gain than controls (6.99 vs 4.43 g, P = 0.0431). HF/HS mice had significantly greater fasting serum insulin (1.21 vs 0.32 ng/mL, P = 0.0401), HOMA-IRscores (7.38 vs 2.7, P = 0.008), cholesterol (130.4 vs 84.25 mg/dL, P = 0.0001)and serum ALT (52.7 vs 31 U/L, P = 0.018). HF/HS livers displayed microvesicular steatosis at 4 weeks with a tendency towards macrovesicular steatosis at 6 weeks. Twenty percent of HF/HS livers contained necroinflammatory foci consistent with nonalcoholic steatohepatitis by 6 weeks vs 0% in controls.Unexpectedly, hepatic expression of TNF-a was not different between the 2 groups.The HF/HS diet is an efficient means of inducing obesity and features of metabolic syndrome over a short period of time in male C57BL/6 mice. Hepatic transcriptional regulation of TNF-a does not appear to play a role.