2011 ADA Posters 1261-2041.indd - Diabetes

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were improved by fenofi brate and pioglitazone. High fat diet induced TG accumulation in skeletal muscle was also decreased 20% by fenofi brate and 24% by pioglitazone. ATGL protein expression was respectively reduced 40% and 18% in adipose tissue and skeletal muscle of HFD rats and was increased after pioglitazone treatment in these tissues. ATGL was increased in skeletal muscle but has no change in adipose tissue by fenofi brate. Fenofi brate and pioglitazone treatment improved insulin sensitivity and increased ATGL protein and coincide with decreased TG content in skeletal muscle. These fi ndings suggest that fenofi brate and pioglitazone ameliorate insulin resistance through decreased ectopic TG content mediated by increased ATGL in mainly tissues. Supported by: National Natural Science Foundation of China Project (30670989) 1831-P Fenofi brate Involves in CCK-Induced Reduction of Food Intake in Rats YING HAN, MI-KYOUNG PARK, SO-YOUNG PARK, SU KYUNG PARK, DUK KYU KIM, HYE-JEONG LEE, Busan, Republic of Korea Fenofi brate has been reported to decrease food intake independent of leptin in rodents. We hypothesized that fenofi brate might decrease food intake via cholecystokinin (CCK) dependent pathway. Otsuka Long-Evans Tokushima fatty (OLETF) rats, which genetically lack CCK receptor as a result of mutation, were divided into OLETF-fenofi brate group (n=5) and OLETFcontrol group (n=5). OLETF-fenofi brate group was fed with standard rat chow and fenofi brate (30mg/kg/day) and OLETF-control group was only fed with standard rat chow for the same period as control. Long-Evans Tokushima Otsuka (LETO) rats which have normal CCK receptor, as control groups to OLETF rats, were also divided into LETO-fenofi brate group (30mg/kg/day) (n=5) and LETO-control group (n=5). After 11 weeks of fenofi brate treatment, food intakes of the fenofi brate group were signifi cantly decreased than those of the control group in the LETO rats (P< 0.05), but there was no signifi cant difference in the OLETF rats. The levels of blood β-ketone, plasma leptin, and fasting blood sugar (FBS) did not show signifi cant difference between the fenofi brate and control groups neither in the LETO rats nor in the OLETF rats. To investigate the expression of CCK by fenofi brate, the protein level of CCK were analyzed with small intestinal tissue of the rats. Fenofi brate treatment groups showed that the protein levels of PPARa and CCK were signifi cantly increased in the small intestine than control groups both in the LETO and OLETF rats. To examine the expression of CCK by fenofi brate, the Caco-2 cells, intestinal epithelial cell line, were cultured in the presence of fenofi brate for 24 hours. Fenofi brate treatment signifi cantly increased the protein expressions of PPARα and CCK in the Caco-2 cells. In conclusion, fenofi brate treatment decreased food intake in the LETO rats which have normal CCK receptor, but not in the OLETF rats which lack CCK receptor. The possible anorexigenic mechanism by fenofi brate might be up-regulation of CCK in the small intestine. 1832-P High Free Fatty Acids Level Related with Microalbuminuria in Obese Rats XIAO DONG SUN, YE RONG YU, LI NA HAN, BEN WANG, Chengdu, China It is known that obesity is associated with microalbuminuria (MAU), which is not only an early manifestation of kidney damage, but also an independent risk factor for ischemic cardiovascular disease. High free fatty acids (FFAs) level is a common feature of obesity and can cause impaired endotheliumdependent vasodilatation (EDV). We hypothesized that increased release of FFAs from excessive visceral fat accumulation is related to increased urine albumin excretion and reduced circulating FFAs level by fenofi brate has renal protective effects in MAU by improving endothelial dysfunction in diet-induced obese rats. Male Wistar rats 4 weeks in age were randomly divided into three groups. The rats in the control group, obesity group and fenofi brate group were fed with normal diet, high-fat diet, and high-fat diet plus fenofi brate (100mg/kg/d), respectively. At the end of 24 weeks, body weight increased 32.8% in obese rats compared to control group. The serum FFAs and TG levels increased signifi cantly in obese rats. Fenofi brate intervention decreased serum FFAs and TG levels by 43.4% and 48% respectively, accompanied by reduced ratio of perirenal fat to body weight (PF/BW) and visceral fat to body weight(VF/BW). Urinary albumin/ creatinine ratio (ACR) increased in obese rats (56.09±22.64 VS 19.52±7.30 mg/g, P
Integrated Physiology/ Obesity POSTERS reported in humans. Thus, fructose-fed rhesus monkeys represent a novel nonhuman primate model useful for investigating the pathophysiology, prevention, and treatment of the metabolic and infl ammatory changes that lead to an increased risk for type 2 diabetes and atherosclerotic cardiovascular disease. Supported by: NIH Grants R21 AT250099 and R21 AT003645 <strong>ADA</strong>-Funded Research 1835-P Lack of Inteferon-γ Results in Reduced Body Weight and Better Glucose Tolerance NICOLE WONG, BARBARA C. FAM, GITTA R. CEMPAKO, GREGORY R. STEINBERG, THOMAS T.W. KAY, JOSEPH PROIETTO, SOFIANOS ANDRIKOPOULOS, Heidelberg Heights, Australia, Hamilton, ON, Canada, Fitzroy, Australia Obesity is a chronic low-grade infl ammatory disease that is caused by increased energy intake and reduced energy expenditure. Studies using animal models with deletion of infl ammatory cytokines have produced confl icting results with some showing increased weight gain and others showing no effect or even reduced body weights. Clearly more work is necessary to understand the role of cytokines on body weight control. Interferon-gamma (IFNγ) is a cytokine derived from T-cells that plays an important role in the innate and adaptive immune response particularly to viral infections. Emerging evidence suggests that increases in the T-cell population in adipose tissue may contribute to obesity and the associated metabolic syndrome. Recent studies have shown that IFNγ was increased with obesity in both human and rodent models while defi ciency of IFNγ resulted in better glucose tolerance in mice. However, how IFNγ affects glucose tolerance is not known. The aim of this study was to assess the effects of IFNγ on both body weight and glucose metabolism using a global knockout mouse model. To do this, male IFNγ -/- and wild-type C57BL/6 mice were monitored for 20 weeks for body weight, food intake and physical activity on a standard rodent chow diet (3.3 kcal/g). At the end of the study, IPGTT, ITT and hyperinsulinaemic/euglycaemic clamps were performed. Expression levels of arcuate nucleus NPY, AgRP and POMC mRNA as well as circulating leptin levels were also determined. The results show that IFNγ -/- mice had reduced weight gain associated with decreased food intake and increased physical activity. NPY and AgRP mRNA expression was reduced, while POMC mRNA expression was increased as were plasma leptin levels. This led to improved glucose tolerance and insulin sensitivity due to greater suppression of endogenous glucose output, associated with decreased hepatic glucose-6-phosphatase activity. We conclude that global deletion of IFNγ in mice resulted in reduced body weight associated with negative energy balance, glucose tolerance and improved hepatic insulin sensitivity. Our fi ndings demonstrate that IFNγ plays a critical role in the regulation of body weight and subsequently glucose metabolism. 1836-P Neuronal Rictor Deletion Leads to Obesity, Growth Defects and Glucose Intolerance HEIDI E. KOCALIS, RICHARD L. PRINTZ, KEVIN D. NISWENDER, Nashville, TN Insulin has pleiotropic effects in the central nervous system (CNS), and neuronal resistance to insulin is implicated in the pathogenesis of obesity and dysglycemia. Akt is a down-stream mediator of insulin action on growth and metabolism. Akt is activated via phosphorylation at serine473 by the rapamycin-insensitive companion of TOR (Rictor) containing complex, mTORC2, in addition to PDK1 phosphorylation at threonine308. The role of mTORC2 signaling targets in CNS regulation of energy homeostasis is not well established. Given the role of Akt in energy and glucose homeostasis, and the role of mTORC2 in Akt activation, we hypothesized that neuronal Rictor gene deletion would lead to obesity and glucose intolerance. Cre-Lox P mediated deletion in neurons (Nestin-Cre) lead to gene dose dependant reductions in Rictor mRNA, and signifi cantly reduced serine473 phosphorylation in null mice. Null mice displayed a profound growth defect that resolved by 12 weeks of age, after which, body weight and length were similar to controls. After 20 weeks of chow diet feeding, het mice gained 68% (11.1±0.6g, P
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2011 ADA Posters 1261-2041.indd - Diabetes

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