Developmental programming by high fructose decreases phosphorylation efficiency in aging offspring brain mitochondria, correlating with enhanced UCP5 expression

作者：Mortensen Ole H^*; Larsen Lea H; Orstrup Laura K H; Hansen Lillian H L; Grunnet Niels; Quistorff Bjorn

来源：Journal of Cerebral Blood Flow and Metabolism, 2014, 34(7): 1205-1211.

DOI：10.1038/jcbfm.2014.72

• aging
• mitochondria
• brain development
• energy metabolism
• gene regulation

Fructose has recently been observed to affect brain metabolism and cognitive function in adults. Yet, possible late-onset effects by gestational fructose exposure have not been examined. We evaluated mitochondrial function in the brain of aging (15 months) male offspring of Fischer F344 rat dams fed a high-fructose diet (50% energy from fructose) during gestation and lactation. Maternal fructose exposure caused a significantly lower body weight of the offspring throughout life after weaning, while birth weight, litter size, and body fat percentage were unaffected.-Isolated brain mitochondria displayed a significantly increased state 3 respiration of 8%, with the substrate combinations malate/pyruvate, malate/pyruvate/succinate, and malate/pyruvate/succiriate/rotenone, as well as a significant decrease in the P/O-2 ratio, compared with the control. Uncoupling protein 5 (UCP5) protein levels increased in the-fructose group compared with the control (P=0.03) and both UCP5 mRNA and protein levels were inversely correlated with the P/O-2 ratio (P=0.008 and 0.03, respectively), suggesting that UCP5 may have a role in the observed decreased phosphorylation efficiency. In conclusion, maternal high-fructose diet during gestation and lactation has long-term effects (fetal programming) on brain mitochondrial function in aging rats, which appears to be linked to an increase in UCP5 protein levels.

• 出版日期2014-7