Dietary fatty acids modulate CNS plasticty via protein kinase‐C

Many recent studies have demonstrated a significant relationship between metabolic diseases (e.g., diabetes) an impaired cognitive function. Brain protein kinase‐C (PKC) has long been implicated in the production of normal LTP/LTD. Additionally, PKC and its downstream signaling pathways (e.g., MARCKS) are known to play important roles in learning and memory. Importantly, numerous recent studies have demonstrated that PKCs attenuate insulin and metabolic signaling in peripheral tissues, including fat, liver and muscle. Here we assessed the hypothesis that CNS PKC isoforms mediated the deleterious effects of diets high in saturated fats (HFS) on CNS function in rats and mice. Specifically, we found that HFS increased membrane localization of PKC in both hypothalamus and hippocampus. This was associated with impaired hypothalamic insulin and leptin signaling, including increased food intake and development of obesity. Additionally, HFS altered membrane‐localization of PKCs in hippocampus, which was associated with decreased performance on spatial and working‐memory tests in rats. These results suggest that PKC mediates the deleterious effects of saturated‐fat diets on CNS function in ways similar to insulin resistance in the periphery. These results further suggest that dietary fats impair CNS plasticity by directly influencing PKC localization and function in several nuclei. Therefore, PKC may offer a novel unifying mechanism by which diets high in saturated fats promote both peripheral and central metabolic disease.