SAT-LB032 Young Adult LEW.1WR1 Rats Develop Increased Glucose Intolerance on a Moderately Increased Sucrose Diet

Abstract

FAT10 is an ubiquitin-like protein and Type 1 Diabetes (T1D) susceptibility gene that may play a role in age-related inflammation, adiposity, and cancer risk. The LEW.1WR1(1WR1) rat overexpresses FAT10 and has higher fasting concentrations of blood insulin and triglyceride during the induction of T1D. FAT10 is hypothesized to play a role in the expression of adipogenic genes; however, it is unclear if overexpression of FAT10 directly affects insulin sensitivity and glucose metabolism. We hypothesize that young adult 1WR1 rats will have increased glucose intolerance due to the poor regulation of insulin secretion which over time leads to reduced insulin sensitivity and increased adiposity. To test this hypothesis, we monitored glucose and insulin tolerance by glucose (GTT) or insulin tolerance (ITT) test and weight gain throughout 12 weeks on high fat and high sucrose (HFD) or moderate sucrose (MS) diet. The LEW/ssNHsd (SsNHsd) rat serves as a control rat. All experiments contain seven rats per group. We observed that at four weeks, the HFD diet rat groups had increased but non-significant fasting blood glucose levels during an ITT (109 +/- 4 mg/dL 1WR1-MS; 113 +/- 5 mg/dL SsNHsd-MS; 132 +/- 6 mg/dL 1WR1 HFD; or 131 +/- 13 mg/dL SsNHsd-HFD.) At ten weeks, the 1WR1-MS rats were more glucose intolerant than the control SsNHsd-MS rat (311.7 +/- 64 mg/dL vs. 194 +/- 53 mg/dL; p=0.09.) We compared the eight week GTT of the 1WR1-MS rats to a GTT before starting the diets (zero weeks) and the thirty minute time points are significantly different for the 1WR1-MS after 8 weeks on the MS diet compared to both the 1WR1-MS and SsNHsd-MS prior to the MS diet ( 164 +/- 27 mg/dL zero weeks 1WR1; 167 +/- 26 mg/dL zero weeks SsNHsd; 311 +/-64 mg/dL eight weeks 1WR1-MS p< 0.0001). 1WR1 rats on both diets also gained weight at similar rates, yet the total abdominal fat mass of the 1WR1-MS rats was not increased compared to the SsNHsd-MS (17.43 +/- 3.48 g 1WR1-MS vs. 16.42 +/- 2.73 g SsNHsd-MS p=0.94 and 24.64 +/- 4.27 g 1WR1-HFD p=0.004) and 1WR1 rat epididymal fat was not significantly different between the two diets compared to the significant difference in SsNHsd rats groups (5.85+/-1.01 1WR1-MS vs. 7.27+/- 1.42 1WR1-HFD p=0.07; 4.63 +/- 0.81 vs. 6.77 +/- 0.65 p=0.0052.) This data suggests that metabolic shifts are occurring in the 1WR1 rat, due to either increased sucrose intake or aging. These shifts reflected the increased glucose intolerance after eight weeks and the changes in abdominal fat pads relative to body mass. This study lays the groundwork for characterizing how alterations in FAT10 increase metabolic dysfunction through aging, glucose metabolism, insulin secretion/signaling, and lipid metabolism/catabolism. Unless otherwise noted, all abstracts presented at ENDO are embargoed until the date and time of presentation. For oral presentations, the abstracts are embargoed until the session begins. Abstracts presented at a news conference are embargoed until the date and time of the news confere...