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A Western Diet Influences Ventilation in a Sex‐Specific Manner and Prevents Expression of Respiratory Neuroplasticity in Adult Rats

Estrogen impacts neuroplasticity in multiple areas of the central nervous system including within respiratory neural networks. Previous research from our group established that estrogen is necessary to permit expression of phrenic long‐term facilitation (pLTF), a form of respiratory neuroplasticity induced by acute, intermittent hypoxia (AIH). Many factors influence circulating estrogen levels such as age, gender, and diet. Specifically, the Western Diet is associated with increased levels of circulating estrogen in post‐menopausal women. Common to cultures of the Western Hemisphere, the Western Diet is characterized by high intakes of red and processed meats, sweets, fried foods, and refined grains with the addition of a high intakes of sugar, salt, omega 6 fatty acids, and a reduction of omega 3 fatty acids. Since the Western Diet is associated with high estrogen levels, and estrogen appears to play a critical role in expression of respiratory neuroplasticity, we assessed whether rats fed a Western Diet would have altered respiratory function and expression of AIH‐induced pLTF. Experimental rats of both sexes were fed a Western Diet in pellet form for 12 weeks and compared to rats consuming standard pellet chow. Weekly whole body plethysmography was used to measure ventilation and changes in ventilatory responses over time. At the conclusion of 12 weeks, AIH‐induced phrenic LTF was measured in anesthetized, vagotomized, and mechanically ventilated rats. Surprisingly, neither sex exhibited a change in body weight in response to the 12‐wk Western Diet, nor was baseline ventilation different between experimental groups within the same sex. However, with hypoxic challenge, male rats on the Western Diet showed lower breathing frequency and higher tidal volumes, while females on the Western Diet exhibited the opposite effects. Also, AIH‐induced pLTF was abolished in male and female Western Diet rats despite an increase in circulating estrogen levels in Western Diet Rats as measured by ELISA assay. These preliminary data suggest that the Western Diet may induce progressive changes in ventilation and loss of respiratory neuroplasticity independent of increased circulating estrogen levels.