A western diet influences ventilation and dampens respiratory neuroplasticity in a sex specific manner
Authors: Barok Rebecca , Grittner Jessica , Dougherty Brendan 
Published: May 2023

Acute intermittent hypoxia (AIH) induces neuroplasticity in the respiratory system. Specifically, AIH can lead to a progressive increase in respiratory neural activity known as long-term facilitation (LTF) or a sustained increase in minute ventilation in awake, freely-behaving rats, known as ventilatory long-term facilitation (vLTF). Previous work from our lab demonstrates that estrogen signaling is necessary for both types of AIH-induced respiratory neuroplasticity in adult female rats. Both forms of neuroplasticity only occur during stages of the estrous cycle with high levels of circulating estrogen. Further, removing the ovaries, the primary source of circulating estrogen, eliminates both forms of AIH-induced plasticity and estrogen supplementation is sufficient to bring it back. These collective results provide strong evidence that estrogen is critical for AIH-induced plasticity in females and prior reports suggest that estrogen is necessary for AIH-induced plasticity in adult male rats as well. Many biological factors influence estrogen levels such as age, gender, and diet. In fact, a Western diet is associated with increased levels of circulating estradiol in both men and postmenopausal women. The Western Diet is defined by high intakes of red and processed meats, sweets, fried food, and refined grains as well as high intakes of sugar, salt, omega-6 fatty acids, and a reduction in omega-3 fatty acids. Because the Western Diet is linked with increased estrogen, and estrogen is essential to the expression of respiratory neuroplasticity, we examined the impact of Western Diet on respiratory function and the expression of respiratory neuroplasticity (LTF and vLTF). Rats of both sexes were placed on a diet consisting of Western Diet pellets or standard chow for 12 weeks. Whole-body plethysmography was used to measure ventilatory responses over the course of the diet. After 12 weeks, plethysmography data showed no change in normoxic ventilation in either sex over the course of the diet. However, in response to hypoxia (12% and 9% O2), there appeared to be a sex-specific pattern of respiratory adaptation, with male Western Diet rats showing an increase in tidal volume, while the females showed a decrease in tidal volume but an increase in respiratory frequency with hypoxia. Preliminary findings suggest that the Western diet had a significant blunting effect on the expression of AIH-induced LTF as well. Of note, the diet did not increase body mass in either sex but did alter circulating estrogen levels in a sex-specific manner. These findings indicate that a Western Diet may influence respiratory function in a sex-specific manner and may impede the induction of respiratory neuroplasticity. UMN Rehabilitation Science Graduate Program, NHLBI R01HL146477, Craig H. Neilsen Foundation, and the UMN Medical School, Division of Physical Therapy This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.