Abstracts / Appetite 52 (2009) 815–868 833 Maternal high-fat diet increases adiposity and glucose intolerance in adult offspring of obesity-resistant (DR) rats J.B. FRIHAUF 1,2,* , E.M. FEKETE 1,3 , E.P. ZORRILLA 1,2 1 CNAD, TSRI, La Jolla, CA, USA 2 UCSD Neurosciences Group, La Jolla, CA, USA 3 Inst. of Physiology, Pécs University Medical School, Pécs, Hungary The present study tested the hypothesis that early exposure to high-fat diet (HF) increases adult obesity risk even in genetically resistant animals. Female diet-induced obesity prone (DIO) and resistant (DR) rats were fed HF or low-fat (LF) diet for 6 weeks before mating and then through weaning. Most DIO females fed HF did not yield litters. Female offspring from other groups (DIO/LF, DR/LF, DR/HF) were weaned onto chow and studied as adults. Adult DR/LF, DR/HF, and DIO/LF offspring showed similar chow intake, yet DR/HF weighed more and were fattier than DR/LF offspring. DIO/LF rats were heaviest and fattiest. Fasting blood glucose (BGL), leptin and insulin levels were highest in DIO/LF rats, but DR/HF offspring also showed higher fasting leptin levels than DR/LF rats. During an oral glucose tolerance test, DR/HF rats showed a slower decline in BGL and higher insulin than DR/LF rats. Rats were then fed puri- fied HF or LF diet for 4 weeks; groups did not differ in normalized energy intake or lean mass gain. When fed either diet, DIO/LF rats gained more fat mass than DR rats. DR/HF rats became fattier when fed the HF diet, unlike HF-fed DR/LF rats, which resisted fat gain. Adult HF diet exposure also increased fasting BGL in DR/HF, but not DR/LF, offspring, with similar trends for leptin and insulin. Thus, an early HF diet environment may increase risk for adult obesity and glucose intolerance despite genetic resistance and may impair reproduction in genetically-prone individuals. doi:10.1016/j.appet.2009.04.078 Sympathetic system controls feeding-induced mobilization of NAPE and OEA in the small intestine J. FU 1,* , A. GUIJARRO 1 , G. ASTARITA 1 , G.J. SCHWARTZ 3 , D. PIOMELLI 1,2 1 University of California, Irvine, CA, USA 2 Italian Institute of Technology, Genoa, Italy 3 Albert Einstein College of Medicine, Bronx, NY, USA N-acylphosphatidylethanolamine (NAPE) and oleoylethanolamide (OEA) are produced by the upper small intestine in response to food intake and have been proposed to serve as satiety hormones through local (OEA) and systemic (NAPE) actions. Previous studies have shown that intestinal NAPE and OEA levels decrease during fasting and rebound after re-feeding. However, the sensory neural control of this response remains unknown. To investigate the role of autonomic afferents in the intestinal production of NAPE and OEA, we examined whether pharmacological or surgical blockade of sympathetic activity affects feeding-induced intestinal production of these molecules. The results show that feeding-induced OEA mobilization in the small intestine is blocked by  adrenergic antagonist, specifically by 2-selective adrenoceptor antagonist, but is not affected by 1, 3 or  adrenoceptor antagonists. The effect of 2 adrenoceptor antagonist on feeding-induced OEA mobilization is accompanied by reduction of OEA precursor NAPE and decreased activity of the OEA-synthesizing enzyme NAPE-specific phospholipase D (NAPE-PLD). Furthermore, the feeding-induced production of NAPE and OEA in the small intestine is completely abolished in rats in which the splanchnic nerves had been transected by removing the celiac-superior mesenteric ganglion. The results suggest that sympathetic activity facilitates the biosynthesis of NAPE and OEA induced by food intake in the small intestine. doi:10.1016/j.appet.2009.04.079 Downstream signaling mechanisms of arcuate nucleus malonyl-CoA in the hypothalamic control of energy balance S. GAO 1,2,* , A. BARR 1 , M. KEMM 2 , F. HEGARDT 3 , T. MORAN 2 , G. LOPASCHUK 1 1 University of Alberta, Edmonton, AB, Canada 2 The Johns Hopkins University School of Medicine, Baltimore, MD, USA 3 University of Barcelona, Barcelona, Spain Malonyl-CoA in the hypothalamic arcuate nucleus (Arc) has recently emerged as a mediator in the control of food intake and energy balance. The downstream signaling of Arc malonyl-CoA is largely unknown, although carnitine palmitoyltransferase-1 liver- isoform (CPT-1A) is proposed as a target. To clarify such a role for CPT-1A, we activated the CPT-1A in the Arc by stereotaxic injection of an adenovirus expressing CPT-1A into the Arc of rats. Activa- tion of Arc CPT-1 produced anorectic actions, which was evident from day 3 through day 9 following the virus injection. The AMPK signaling in the Arc was not affected by the altered activity of CPT-1. The increased activity of CPT-1 reduced the levels of long- chain acyl-CoA’s (LCFA-CoA’s), CPT-1 substrates, and increased the malonyl-CoA level in the Arc. LCFA-CoA’s are allosteric inhibitors of acetyl-CoA carboxylase (ACC) that produces malonyl-CoA. Thus, the observed increase of malonyl-CoA level may be accounted for by the de-inhibition of ACC following decreased LCFA-CoA’s, which is in line with our finding that intra-hypothalamic delivery of palmi- tate rapidly stimulated feeding and lowered the malonyl-CoA level. In the Arc, LCFA-CoA’s were increased with a decrease of malonyl- CoA by fasting and LCFA-CoA’s were reduced with an increase of malonyl-CoA by refeeding. Our data suggest that target(s) other than CPT-1A and long-chain acyl-CoA’s exist in mediating Arc malonyl-CoA control of food intake and energy balance. doi:10.1016/j.appet.2009.04.080 Glucose-conditioned preferences in taste-impaired TRPM5 knockout mice D.S. GLASS 1,* , R.F. MARGOLSKEE 2 , A. SCLAFANI 1 1 Brooklyn College CUNY, Brooklyn, NY, USA 2 Mount Sinai School of Medicine, New York, NY, USA Knockout (KO) mice missing the TRPM5 taste signaling protein are indifferent to dilute sugar solutions (0.5–4%) but prefer con- centrated solutions (8–32%) in 24-h tests. This preference has been attributed to the post-oral actions of the sugar. This study inves- tigated oral and post-oral influences on glucose preference in KO mice. Food and/or water deprived KO mice, unlike C57BL/6J wild- type (WT) mice, were indifferent to 8% glucose (vs. water) in 60-s two-bottle tests. Yet, like WT mice, they consumed more glucose than water in 1-bottle, 30-min tests. KO mice, like WT mice, also consumed more glucose than water in 24-h tests and strongly pre- ferred (95%) glucose in subsequent 24-h two-bottle tests. This 24-h preference may represent a learned association between TRPM5- independent orosensory (texture, odor, taste) and viscerosensory sugar stimuli. Since TRPM5 and other taste signaling elements are found in intestinal cells, we next determined if KO mice show a nor- mal post-oral conditioning response to sugar. Water-deprived KO and WT mice were trained 1h/day to drink flavored water (grape, cherry) paired with intragastric infusions of 16% glucose or water. After 6 one-bottle training sessions, KO, like WT mice, significantly preferred the glucose-paired flavor. Yet, when given 1-h oral glu- cose vs. water tests, the KO mice were indifferent to the sugar. Thus, KO mice have a substantial sweet taste deficit but an intact post-oral flavor conditioning response to glucose. doi:10.1016/j.appet.2009.04.081