the ASP1941 10 mg/kg group (P
Integrated Physiology/ Obesity POSTERS indicates that MβKO mice have increased adiposity. Signifi cantly elevated serum leptin levels were observed in MβKO mice, despite the fact that their hematological parameters, serum insulin and glucagon were within normal ranges. Leptin-suppressed food intake and body weight reduction in MβKO mice were signifi cantly less than WT mice, which further suggest that knocking out C/EBPβ in macrophages impairs leptin sensitivity in mice. The expression of key lipogenic genes was signifi cantly increased in livers and white fats of MβKO mice. On the other hand, the levels of F4/80 and other macrophage markers were remarkably decreased in white fat, liver and skeletal muscle of chow or high fat diet-fed MβKO mice. Using bone marrow-derived macrophages, we found the expression of alternative activated macrophage markers were signifi cantly decreased in C/EBPβ defi cient macrophages at basal and after IL-4 induction. These results indicate that 1) C/EBPβ plays an important role in macrophage activation and tissue infi ltration; 2) residential macrophages may actively regulate energy metabolism. Supported by: NIDDK <strong>ADA</strong>-Funded Research & 1819-P Sterol Regulatory Element Binding Protein-1c (SREBP-1c) Is Different ly Regulated by TNF-Related Apoptosis Inducing Ligand (TRAIL) in High-Fat Diet Induced Obese Mice SO-YOUNG PARK, MI-KYOUNG PARK, YING HAN, SU KYUNG PARK, DUK KYU KIM, HYE-JEONG LEE, Busan, Republic of Korea TRAIL is a member of TNF family of cytokines, which exist either as type II membrane or as a soluble protein. Although the well-characterized activity of TRAIL is represented by its anti-cancer activity, little is known regarding the effects of TRAIL on metabolic pathways. To address this point, we studied in vivo effects of TRAIL in high-fat diet induced obese mice. SREBP-1c is a transcription factor which is synthesized as a precursor in the membranes of the endoplasmic reticulum and which requires post-translational modifi cation to yield its transcriptionally active nuclear form. SREBP-1c induces the expression of a family of genes involved in glucose utilization and fatty acid synthesis. C57BL/6 Mice were classifi ed into two groups and fed with the normal (ND) and high-fat diet (HFD) for up to 22 weeks. All mice of the high-fat diet group developed obesity and type 2 diabetes. Seven days after adenoviral-mediated hTRAIL (ad.hTRAIL) and control GFP (ad.GFP) delivery to each groups, mice were killed and samples were collected and analyzed. The expression of ad.hTRAIL was determined by western blotting with liver tissue. Overexpression of ad.hTRAIL signifi cantly decreased accumulation of hepatic lipid and plasma lipid profi les in HFD mice. The expression of hepatic SREBP-1c was increased by ad.hTRAIL in ND mice, compared with ad.GFP. The expression of SREBP-1c was increased in HFD mice, compared with ND mice as expected by high lipogenic activity. However, the expression of SREBP-1c was decreased by ad.hTRAIL in HFD mice, compared with ad.GFP in HFD mice. The target genes of SREBP-1c, fatty acid synthase, acetyl CoA carboxylase, and stearoyl CoA desaturase 1 were altered signifi cantly by the changes of the expression of SREBP-1c. Taken together, TRAIL alters the expression of lipogenic genes through SREBP-1c and the expression of SREBP-1c is differently regulated by TRAIL in response to high-fat diet. These fi ndings suggest that TRAIL might have a novel function for lipid metabolism via SREBP-1c related mechanism, modulating lipogenesis in lipid-rich environment and improving hepatic steatosis. & 1820-P Roux-en-Y Gastric Bypass Prevents the Progression to <strong>Diabetes</strong> in Obese Mice DENG-PING YIN, QIANG GAO, LIAN-LI MA, PHILLIP E. WILLIAMS, OWEN MC- GUINNESS, ALVIN C. POWERS, DAVID H. WASSERMAN, NAJI N. ABUMRAD, Nashville, TN Obesity is associated with insulin resistance and increased risk of developing type 2 diabetes (T2D). C57BLKS-db/db (BKS-db) mice, a model of insulin resistance, develop diabetes with aging. We tested whether Rouxen-Y gastric bypass (RYGB), an effective therapy for morbid obesity and T2D in humans, can prevent disease progression in young pre-diabetic (6-7 wks old, n=6) and/or reverse diabetes in older diabetic BKS-db mice (14-15 wks old, n=4), as well as in wild-type STZ-induced diabetic mice (FVB) expressing luciferase under the control of the mouse insulin promoter (MIP-Luc, n=6). All BKS-db mice that underwent RYGB were compared to pair-fed BKSdb mice that underwent a sham surgery (n=4/group). In the young BKS-db mice, RYGB and pair-fed sham-treated groups experienced similar weight loss and gain and changes in fat mass throughout the fi rst eight wks. RYGB in young BKS-db mice maintained normoglycemia (blood glucose levels < 200mg/dl) and improved glucose tolerance during intraperitoneal glucose For author disclosure information, see page 785. OBESITY—ANIMAL CATEGORY A492 tolerance tests (area under curve) up to 8 wks after surgery (compared with pair-fed sham-treated mice, 993±189 vs 1856±169 at 1 wk, p