1348-P: Roux-en-Y Gastric Bypass Prevents Obesity-Induced Fatty Liver by Modulating Liver Lipocalin Type Prostaglandin D2 Synthase Expression

The obesity epidemic is associated with an increased prevalence and severity of type 2 diabetes, cardiovascular disease, and nonalcoholic fatty liver disease (NAFLD) . Bariatric surgery has become a widely accepted treatment for individuals with severe obesity and obesity related health problems. Previous studies from our lab have implicated the role of lipocalin-type prostaglandin D2 synthase (L-PGDS) in adipose tissue dysfunction and NAFLD. Our lab has also shown the effect of Roux-en Y gastric bypass (RYGB) on body weight changes, improvement to insulin sensitivity and adipose tissue physiology. In the current study, we examined the effects of L-PGDS using both diet-induced obesity (DIO) and RYGB models. We found reduced expression of L-PGDS in liver of DIO mice after 14 weeks on high fat diet. We then performed RYGB surgery in DIO mice and compared the effects of diets (normal chow and HFD for 6 weeks) on post-operative outcomes of RYGB. Our results show that both surgery and diet contribute to the substantial improvement in liver weight and HOMA-IR. H&E images of liver sections also demonstrate that both diet and surgery play significant roles in reversal of NAFLD. Interestingly, we only found significant increase to liver L-PGDS expression after RYGB when HFD is administered. We conclude that both surgery and diet plays a significant role in modulating the expression of L-PGDS in liver of obese mice. Thus, our study shows that L-PGDS may serve as a novel therapeutic target in treatment of obesity and NAFLD.