Expression of IGF2R, IGF2, TGF, and uPAR in a rat model of obesity
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We tested the hypothesis that induction of obesity in lean Long Evans Tokushima Otsuka (LETO) and obesity-prone Otsuka Long Evans Tokushima Fatty (OLETF) would cause the insulin growth factor 2 receptor (IGF2R) and factors it regulates, including insulin growth factor 2 (IGF2), transforming growth factor beta (TGFB), and urokinaseplasminogen receptor (uPAR) to be changed in expression away from a pro-angiogenic state. This would arise from an increase in IGF2R and TGFB, and a decrease in IGF2 and uPAR. LETO and OLETF rats were raised from age 4 to 32 weeks, with each strain subdivided into a control diet (CON) and high fat diet (HFD) group. We also raised a cohort of OLETF HFD rats which either underwent weight control interventions (exercise training (EX) or calorie restriction (CR)) or did not undergo intervention (sedentary (SED)). Interventions began at age 20 weeks and continued until 32 weeks. We found significant increases in both body weight and body fat percentage, and in decrease in capillarity in both biceps brachii (BB) and vastus lateralis (VL) muscle, in comparing non-obese to obese animals (p less than 0.05). When examining diet and strain induction of obesity, we found significant increases in body weight and body fat percentage from control lean animals, but with no significant change in capillarity. We did not observe any significant effects on body weight or body fat percentage in EX or CR relative to SED. We observed multiple significant changes in skeletal and adipose feed arteries with obesity induction on IGF2R, IGF2, TGF, and uPAR. However, most of these changes did not occur in accordance with our hypothesis. Overall, we find LETO and OLETF rats to be a viable model for examining mechanisms driving changes in tissue capillarity in obesity, and that the IGF2R system we proposed does not appear to agree with the data. We propose that the IGF2R system is moderated in a static-toproangiogenic state during obesity, and decreases in overall capillarity are driven by other mechanisms.
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