Prolonged fasting causes systematic changes in rats 13COsub2sub breath testing and small molecule metabolomics


Meeting Abstract

P3-135  Tuesday, Jan. 6 15:30  Prolonged fasting causes systematic changes in rats: 13CO2 breath testing and small molecule metabolomics GUZMAN, R/M*; MCCUE, M/D; POLLOCK, E/D; MCCUE, K/E; St. Mary’s Univ; Univ Arkansas; UTHSCSA mmccue1@stmarytx.edu

Measurements of the δ13CO2 in animal tissues are routinely used to make inferences about the extent to which C3 plants and C4 plants contribute to the diets of animals. However a fasting animal’s diet is its own tissues. Interestingly, the body lipids contain measurably lower amounts of 13C than lean tissues (e.g., carbohydrates and proteins). We postulated that changes in the δ13CO2 in the exhaled CO2 of rats would reflect the timing of fasting-induced changes in oxidative substrates and expected the breath would initially become isotopically lighter with increased reliance on lipid oxidation and then heavier during prolonged-starvation. We further tested whether differences in the δ13C of the bulk diet would influence the fasting-induced changes δ13C in the breath. We raised rats (n=23) on diets derived from rice (C3) or corn (C4) for 8 weeks. Rats were fasted for 11 days. Breath samples were collected every 6h and urine was collected daily. We measured the δ13C in tissues from a subset of rats before and after fasting. The breath of prefasting rats resembled that of their lean tissues, and then fell by >2.5 per mil during the first 2 days, almost reaching the values of the body lipids as carbohydrate stores were consumed. After 7 days the δ13C of the breath began to gradually increase with an increased reliance on protein oxidation but never returned to the prefasting values suggesting a balance of lipid and protein catabolism. The isotopic composition of the bulk diet had no effect on the fasting-induced changes in the δ13C of the breath. NMR-based metabolomics also detected systematic changes in the urine metabolites indicative of fasting-induced changes in oxidative substrates. We conclude the 13C-breath testing and urine metabolomics may be useful methods to noninvasively track the physiological progression of fasting.

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