[HTML][HTML] Dietary fructose induces a wide range of genes with distinct shift in carbohydrate and lipid metabolism in fed and fasted rat liver

HY Koo, MA Wallig, BH Chung, TY Nara… - … et Biophysica Acta (BBA …, 2008 - Elsevier
HY Koo, MA Wallig, BH Chung, TY Nara, BHS Cho, MT Nakamura
Biochimica et Biophysica Acta (BBA)-Molecular Basis of Disease, 2008Elsevier
Dietary fructose has been suspected to contribute to development of metabolic syndrome.
However, underlying mechanisms of fructose effects are not well characterized. We
investigated metabolic outcomes and hepatic expression of key regulatory genes upon
fructose feeding under well defined conditions. Rats were fed a 63%(w/w) glucose or
fructose diet for 4 h/day for 2 weeks, and were killed after feeding or 24-hour fasting. Liver
glycogen was higher in the fructose-fed rats, indicating robust conversion of fructose to …
Dietary fructose has been suspected to contribute to development of metabolic syndrome. However, underlying mechanisms of fructose effects are not well characterized. We investigated metabolic outcomes and hepatic expression of key regulatory genes upon fructose feeding under well defined conditions. Rats were fed a 63% (w/w) glucose or fructose diet for 4 h/day for 2 weeks, and were killed after feeding or 24-hour fasting. Liver glycogen was higher in the fructose-fed rats, indicating robust conversion of fructose to glycogen through gluconeogenesis despite simultaneous induction of genes for de novo lipogenesis and increased liver triglycerides. Fructose feeding increased mRNA of previously unidentified genes involved in macronutrient metabolism including fructokinase, aldolase B, phosphofructokinase-1, fructose-1,6-bisphosphatase and carbohydrate response element binding protein (ChREBP). Activity of glucose-6-phosphate dehydrogenase, a key enzyme for ChREBP activation, remained elevated in both fed and fasted fructose groups. In the fasted liver, the fructose group showed lower non-esterified fatty acids, triglycerides and microsomal triglyceride transfer protein mRNA, suggesting low VLDL synthesis even though plasma VLDL triglycerides were higher. In conclusion, fructose feeding induced a broader range of genes than previously identified with simultaneous increase in glycogen and triglycerides in liver. The induction may be in part mediated by ChREBP.
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