Emily E. Noble, PhD - US grants

Project title: Early life sugar consumption: effects on cognitive impairment and susceptibility to obesity PROJECT SUMMARY/ ABSTRACT Obesity and metabolic morbidities associated with obesity have reached epidemic proportions, and children are the fastest growing group affected. Sugar consumption has risen in parallel to obesity rates in the US, and children are the highest sugar consumers of any age group with ~16% of their total daily caloric intake from added sugars. Yet, despite the increases in sugar consumption, surprisingly little is known about the long-term impact of sugar consumption on brain and behavioral outcomes. The central hypothesis of this proposal is that excessive consumption of sugar-sweetened beverages during juvenile and adolescent development increases susceptibility to obesity and metabolic disease during adulthood by altering neurocognitive behaviors and molecular mechanisms related to feeding. Recent mechanistic rodent model studies have identified the juvenile period of development as one of high vulnerability for sugar-related neurocognitive deficits. For example, recent published work from my two co- sponsors reveals that excessive sugar consumption in rats beginning during the juvenile/adolescent period of development but not beginning during early adulthood impairs memory function and increases neuroinflammation in the hippocampus, a brain region that is both involved in learning and memory and feeding behavior. I will test whether early life sugar consumption programs long-lasting memory deficits and susceptibility to obesity during adulthood via changes in the brain epigenome. Using a multispecies translational approach, this proposal is designed to investigate the relationship between early life sugar consumption and neurocognitive dysfunction, including memory impairments and food impulsive behavior. In Aim 1A, I will determine whether early life sugar consumption promotes behavioral traits related to excessive feeding behavior and weight gain using our established rodent model of high fructose corn syrup consumption. Rodents will be tested in behavioral tasks to measure susceptibility to cue-potentiated hyperphagia, food impulsivity, and diet-induced obesity. In Aim 1B I will examine whether early life sugar consumption promotes long-lasting impairments in hippocampal- dependent memory and food impulsivity in conjunction with epigenetic modifications of hippocampal and mesolimbic neural systems related to synaptic plasticity and food reward. Translation of these findings to human populations will ultimately be critical to understanding the full implications of our animal model data. Therefore, Aim 2 will examine the relationship between early life sugar consumption and neurocognitive dysfunction in human children. Parent-child (7-9-years old) pairs will be recruited from the Los Angeles area for a cross-sectional study examining the relationship in children between habitual dietary sugar consumption and cognitive function, including food impulsivity and hippocampal-dependent memory capacity. Collectively, the results from these experiments will determine whether dietary sugar during early life influences behavioral patterns related to the cognitive control of feeding behavior and susceptibility to obesity via epigenetic modifications. Novel findings from these studies may lead to more effective behavioral interventions and policies designed for the treatment and prevention of obesity and metabolic disorders.