Di Natale, M. R. | bioRxiv Science

bioRxiv2024

Magnetic Resonance Imaging of Gastric Motility in Conscious Rats

IntroductionGastrointestinal (GI) magnetic resonance imaging (MRI) can simultaneously capture gastric peristalsis, emptying, and intestinal filling and transit. Performing GI MRI with animals requires anesthesia, which complicates physiology and confounds interpretation and translation from animals to humans. This study aims to enable MRI in conscious rats, and for the first time, characterize GI motor functions in awake versus anesthetized conditions. MethodsWe acclimated rats to remain awake, still, and minimally stressed during MRI. We scanned 14 Sprague-Dawley rats in both awake and anesthetized conditions after voluntarily consuming a contrast-enhanced test meal. ResultsAwake rats remained physiologically stable during MRI, showed gastric emptying of 23.7{+/-}1.4% after 48 minutes, and exhibited strong peristaltic contractions propagating through the antrum with a velocity of 0.72{+/-}0.04 mm/s, a relative amplitude of 40.7{+/-}2.3%, and a frequency of 5.1{+/-}0.1 cycles per minute. In the anesthetized condition, gastric emptying was about half of that in the awake condition, likely due to the effect of anesthesia in halving the amplitudes of peristaltic contractions rather than their frequency (not significantly changed) or velocity. In awake rats, the intestine filled more quickly and propulsive contractions were more occlusive. ConclusionWe demonstrated the effective acquisition and analysis of GI MRI in awake rats. Awake rats show faster gastric emptying, stronger gastric contraction with a faster propagation speed, and more effective intestinal filling and transit, compared to anesthetized rats. Our protocol is expected to benefit future preclinical studies of GI physiology and pathophysiology.

bioengineering↗

bioRxiv2024

Food entrainment in mice leads to sex- and organ-specific responses in nutrient metabolism

Food intake is one of the main zeitgebers in the digestive system; however, little is known about organ- and sex-specific differences in food-driven regulation. We placed male and female C57Bl/6 mice on time-restricted feeding (TRF), limiting the food intake period to 8 hours. Food was added either at dark (ZT12) or light (ZT0) onset for 14 days. Afterwards, an additional 4-hour delay in the feeding period was introduced for half of the mice, and the TRF regime continued for another 14 days. TRF from ZT12 to ZT20 led to the highest weight gain in females but the lowest in males while improving intestinal transepithelial resistance (TEER) in both sexes. However, it also led to the disappearance of food-anticipatory response in several hepatic genes. Delaying the start of TRF until ZT16 led to an increase in weight gain and a decrease in fasting plasma glucose levels in male mice, as well as to strong entrainment of metabolism-related hepatic and duodenal genes in both sexes. The alignment of food intake with the early lights-on phase (ZT0-ZT8) caused only minor changes in physiological responses. However, it did lead to an overall downregulation of hepatic and an upregulation of duodenal and gastric genes, with additional loss of food-anticipatory gene expression in both sexes. Delaying the start of food intake until ZT4 was highly detrimental, causing an increase in fasting blood glucose levels, a decrease in TEER, and further disruptions in gene expression patterns in the stomach and liver. In contrast, the duodenum was able to restore its food-driven gene expression. These results demonstrate that the adjustment to food intake time in mice is highly sex- and organ-specific. Our chosen TRF regimes were not able to synchronize food-anticipatory responses between the liver and gut. Instead, we observed that organs entrain to food intake at different rates.

molecular biology↗