Metabolic study of RIAD mice
T cell activation is inhibited by PKA type I (PKAI) signaling, and disruption of this pathway results in enhanced T effector cell responsiveness. We have created a transgenic mouse model of enhanced T effector cell signaling by using a RI subunit-anchoring disruptor (RIAD) construct under control of distal mouse lck promoter on a C57BL/6 background. The heterozygous transgenic mice (RIAD mice) are lean and healthy at a young age, but starting around 4 weeks, they develop a severely obese phenotype when fed ad libitum. On average, the RIAD mice weighed twice as much healthy wild-type (WT) littermates. Our preliminary data show increased adipocyte size and increased number of adipocytes in the RIAD mice compared to WT littermates. T cell regulation of adipose tissue represents an unstudied pathophysiological mechanism of obesity-associated metabolic disease, and in this study, we wish to further explore the metabolic changes in RIAD mice.
We will feed RIAD mice, age-matched WT mice and a group of ob/ob mice (a well-characterized model of obesity) standard rodent chow or diets calorie-enriched by carbohydrates, fat or proteins for 36 weeks to determine if different sources or calories affect the development of the obese phenotype. In addition, calorie restriction will be performed in an attempt to rescue the phenotype. We will monitor the weight development and feed efficiency, and collect blood samples on a weekly basis (<50µL). Oral-glucose-tolerance-tests (oGTTs) or insulin-tolerance tests (ITTs) will be performed at 6 weeks intervals to trace the development and progression of metabolic dysregulation. Animals will be fasted 4-6 hours prior to the oGGTs and ITTs. As a small pinprick is needed for blood sampling, we expect "light stress/pain" in a few seconds after the pinprick. After the feeding period organ harvesting is a "terminal experiment".
A total of 600 experimental animals (4 different genotype – see "methods" for details) will be used for the metabolic study.
We will feed RIAD mice, age-matched WT mice and a group of ob/ob mice (a well-characterized model of obesity) standard rodent chow or diets calorie-enriched by carbohydrates, fat or proteins for 36 weeks to determine if different sources or calories affect the development of the obese phenotype. In addition, calorie restriction will be performed in an attempt to rescue the phenotype. We will monitor the weight development and feed efficiency, and collect blood samples on a weekly basis (<50µL). Oral-glucose-tolerance-tests (oGTTs) or insulin-tolerance tests (ITTs) will be performed at 6 weeks intervals to trace the development and progression of metabolic dysregulation. Animals will be fasted 4-6 hours prior to the oGGTs and ITTs. As a small pinprick is needed for blood sampling, we expect "light stress/pain" in a few seconds after the pinprick. After the feeding period organ harvesting is a "terminal experiment".
A total of 600 experimental animals (4 different genotype – see "methods" for details) will be used for the metabolic study.