Vitamin A Status Regulates the Development of Obesity and Type 2 Diabetes in Zucker Diabetic Fatty Rats

Abstract Objectives We have shown that vitamin A (VA) status regulates obesity and fuel metabolism in rats. Here, we studied the effects of VA status on the development of obesity and type 2 diabetes in Zucker diabetic fat (ZDF) rats. Methods Zucker Lean (ZL) and ZDF rats at weaning were divided into 6 groups, VA deficient with basal fat (VAD-BF, 0 mg retinyl palmitate (RP)/kg and 22.1% fat energy), VA marginal with BF (VAM-BF, 0.35 mg RP/kg), VA sufficient with BF (VAS-BF, 4.0 mg RP/kg), VAD with high-fat (VAD-HF, 60% fat energy), VAM-HF and VAS-HF diets, and fed for 8 weeks (w). The body mass (BM), and peripheral blood glucose (PBG) were measured weekly. Insulin tolerance test (ITT) and oral glucose tolerance test (OGTT) were done at 6.5 and 7.5 w, respectively. At the end of the feeding, blood, liver and white adipose tissue (WTA) samples were collected. Results VAS-BF ZL and ZDF rats from 6 w had respectively higher BM than VAD/VAM-BF ZL and ZDF rats. VAS-HF ZL and ZDF rats from 4 w had respectively higher BM than VAD/VAM-HF ZL and ZDF rats. The liver/BM and WAT/BM ratios in VAD/VAM-BF/HF ZL and ZDF V rats were respectively lower than that of VAS-BF/HF groups. VAS-BF/HF ZDF rats from 6 w had respectively higher PBG levels than VAD/VAM-BF/HF ZDF rats. In ITT, PBG levels of VAD/VAM/VAS-BF ZL rats dropped until 15 mins. PBG levels of VAD-HF and VAM/VAS-HF ZL rats declined until 30 mins and 15 mins, respectively. PBG levels of VAM-BF and VAS-BF ZDF rats dropped until 15 mins and 5 mins, respectively. PBG levels of VAD-BF ZDF rats start to dropped after 10 mins and stopped after 20 mins. PBG levels of VAD/VAM-HF and VAS-HF ZDF rats dropped until 15 mins and 20 mins, respectively. The OGTT results showed that PBG levels of VAS-BF ZL rats peaked at 10 mins, and VAS-BF/HF ZL rats had respectively higher PBG levels than VAD/VAM-BF/HF ZL rats. PBG levels of all ZDF rats peaked at 60 mins (except for VAS-BF ZDF rats at 30) before dropped. TheOGTT area under the curve values of VAS-BF/HF ZL or ZDF rats were respectively higher than that of VAD/VAM-BF/HF ZL or ZDF rats, and that of VAM-HF ZL rats were higher than that of VAD-HF ZL rats. Conclusions VA statuses affect BM gain in ZL and ZDF rats in BF and HF diets. Reduced VA intake prevents obesity, and type 2 diabetes in ZDF rats. Funding Sources Diabetes Action Research and Education Foundation.