bluuebunny/crossref_metadata_2025_split huggingface dataset:
1966-P: Manipulating Postprandial Bile Acid Concentrations: Effect on GLP-1 Secretion after Roux-en-Y Gastric Bypass
Authors: SVANE MARIA S. , JONSSON ISABELLA , KRISTIANSEN VIGGO BJERREGAARD , KUHRE RUNE E. , WEWER ALBRECHTSEN NICOLAI JACOB , HOLST JENS J. , MADSBAD STEN , BOJSEN-MOLLER KIRSTINE N. 
Published: June 2019

Enhanced glucagon-like peptide-1 (GLP-1) secretion is important for improved glycemic control after Roux-en-Y gastric bypass (RYGB) and higher concentrations of circulating bile acids (BA) have been suggested to be involved. The BA chenodeoxycholic acid (CDCA) stimulates GLP-1 secretion after RYGB in the absence of nutrients. In this study we investigated the effects of oral intake of CDCA or the BA sequestrant colesevelam (COL) on postprandial GLP-1 secretion in RYGB operated subjects. We hypothesized that CDCA would increase secretion and that COL would decrease secretion by reducing re-absorption of endogenous BA. Twelve participants (BMI 31±2 (mean±SEM) kg/m2, age 43±3 years, time from RYGB 4.3±0.5 years, weight loss after RYGB 34±5 kg) were studied in a single-blinded, randomised study with four experimental days: 1) A mixed meal consisting of solid/semisolid components (1523 kJ, 53E% carb, 33E% fat, 14E% prot) 2) Mixed meal added 1250 mg CDCA 3) Mixed meal added COL 3750 mg 4) Mixed meal with COL administered both as 3750 mg tablets the evening before the experiment and as 3750 mg added to the meal. Oral intake of CDCA increased GLP-1 significantly compared with mixed meal alone (p=0.03), whereas neither single (p=0.74) nor double (p=0.28) dosage of COL affected GLP-1 secretion (Incremental AUC (iAUC) GLP-1: Meal: 2792±288 pmol x min, CDCA: 4362±618, COL: 2703±330, COLx2: 3328±380). Plasma glucose and C-peptide (iAUC) decreased after CDCA but both were unchanged after COL administration vs. meal alone. Beta-cell function (AUC C-peptide/AUC plasma glucose) was equal between all study days.
In summary, administration of the exogenous BA CDCA potentiated mixed-meal stimulated GLP-1 secretion after RYGB but did not affect beta-cell function. Administration of the BA sequestrant COL did not affect GLP-1 secretion, glucose concentrations or beta-cell function, suggesting a limited role for endogenous BA for regulation of postprandial glucose metabolism after RYGB.

Disclosure
M.S. Svane: None. I. Jonsson: None. V. Kristiansen: None. R.E. Kuhre: None. N.J. Wewer Albrechtsen: Research Support; Self; Mercodia, Novo Nordisk A/S. Speaker's Bureau; Self; Merck Sharp & Dohme Corp. J.J. Holst: Advisory Panel; Self; Novo Nordisk A/S. S. Madsbad: None. K.N. Bojsen-Moller: None.

Funding
European Research Council (695069)
1967-P: Mild Physiologic Hyperglycemia Impairs Insulin-Mediated Suppression of Plasma Glucagon in Healthy Normal Glucose Tolerant Subjects
Authors: MEROVCI AURORA , CHEN XI , DEFRONZO RALPH A. , TRIPATHY DEVJIT 
Published: June 2019

Hyperglycemia adversely affects skeletal muscle and hepatic insulin sensitivity (glucotoxicity). However, the effect of prolonged hyperglycemia on glucose and insulin-mediated suppression of glucagon is not known. The aim of the present study was to evaluate effect of a chronic (72 hours) physiologic increase (+45 mg/dl) in plasma glucose concentration on the suppression of plasma glucagon concentration in healthy NGT individuals: 12 without family history of T2DM (FH-) (9M/3F, age = 50± 4 years, BMI = 27 ± 1 kg/m2) and 8 with FH of T2DM (FH+) (4M/4F, age = 48±2, BMI = 26±1 kg/m2). Subjects received an OGTT and 2-step hyperglycemic (+125 and +300 mg/dl) clamp (duration of each step = 80 minutes) before and after 72-hour glucose infusion. Plasma insulin and C-peptide concentrations were obtained every 2-5 minutes during each hyperglycemic clamp step and plasma glucagon concentrations were measured every 10 minutes. The ratio of insulin/glucagon was measured and used as an index of insulin-medicated suppression of plasma glucagon. FPG concentration increased from 97±4 to 140±4 mg/dl during the 72-hour glucose infusion. Following chronic glucose infusion, plasma insulin levels were significantly higher during the basal state and during each hyperglycemic clamp step (by 59% and 78%) during the 0-80 and 80-160 min time periods, respectively. There was no difference in plasma glucagon levels following chronic glucose infusion. However, the plasma insulin/glucagon ratio was significantly higher during the fasting state (by 76%) and during the first (by 128%) and second (by 178%) hyperglycemic clamp steps. There was no difference in the effect of chronic glucose infusion on glucagon secretion between FH+ and FH-subjects. These results demonstrate that sustained physiologic hyperglycemia for 72 hours (i.e., glucotoxicity) impairs insulin-mediated suppression of glucagon, and could contribute to fasting and post-prandial hyperglycemia in T2DM patients.

Disclosure
A. Merovci: None. X. Chen: None. R.A. DeFronzo: Advisory Panel; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Elcelyx Therapeutics, Inc., Intarcia Therapeutics, Inc., Janssen Pharmaceuticals, Inc., Novo Nordisk Inc. Research Support; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Janssen Pharmaceuticals, Inc., Merck & Co., Inc. Speaker's Bureau; Self; AstraZeneca, Novo Nordisk Inc. D. Tripathy: None.

Funding
National Institutes of Health
1969-P: Time-Based Internalized Characterization of Exendin-4-Based Glucagon-Like Peptide-1 Receptor-Targeting Imaging Probe
Authors: MURAKAMI TAKAAKI , FUJIMOTO HIROYUKI , FUJITA NAOTAKA , HAMAMATSU KEITA , FUJIKURA JUNJI , INAGAKI NOBUYA 
Published: June 2019

Aims: For the purpose of visualization and quantification of β cells, glucagon-like peptide 1 receptor (GLP-1R)-targeting imaging including single photon emission computed and positron emission tomography (SPECT/PET) has emerged recently. It is well known that internalization of the probes can affect visualization of regions of interest on SPECT/PET. However, the internalization and its effect on β-cell visualization of GLP-1R-targeting probes have not been fully examined. Therefore, we investigated time-based internalized activities of an exendin-4 (Ex4)-based probe, which was developed for clinical GLP-1R-targeting imaging.
Method: [18F]FB(ePEG12)12-Ex4 (18F-Ex4) was synthesized. Rat insulinoma cell line, INS-1 and Human Embryonic Kidney cells 293 expressing human GLP-1R (HEK_GLP-1R) were used as GLP-1R-positive cells. These cells were incubated with 18F-Ex4 (1.48 MBq) for different periods of time (0-120 minutes). Whole cell (WC) and internalized (IC) radioisotope activities were measured by the gamma counter.
Results: WC per incubated probe (IP) activities showed rapid rise within 30 minutes of incubation time and further gradual increase up to 120 minutes in INS-1 and HEK_GLP-1R cells, whereas wild type HEK293 showed no significant WC activity. The WC/IP differences between INS-1 and HEK_GLP-1R cells were significant at the 15-minutes mark (p=0.04) but reduced to insignificant after 30 minutes, although the two cell lines showed significantly different levels of GLP-1R mRNA expressions. IC/IP increased rapidly within 30 minutes and gradually up to 120 minutes. The IC/WC at the 120-minutes mark were significantly higher than those at the 30-minutes mark in both cell lines.
Conclusion: The 18F-Ex4 probe showed rapid uptakes and internalization in GLP-1R-expressing cell lines, which indicates that dual or delayed phases of GLP-1R-targeting imaging may be beneficial. In addition, a time-based hampering effect of GLP-1R-expression levels for β-cell visualization can be suggested.

Disclosure
T. Murakami: None. H. Fujimoto: None. N. Fujita: None. K. Hamamatsu: None. J. Fujikura: None. N. Inagaki: Research Support; Self; Astellas Pharma Inc., Boehringer Ingelheim Pharmaceuticals, Inc., Daiichi Sankyo Company, Limited, Japan Tobacco Inc., Kyowa Hakko Kirin Co., Ltd., Merck Sharp & Dohme Corp., Mitsubishi Tanabe Pharma Corporation, Novartis Pharmaceuticals Corporation, Ono Pharmaceutical Co., Ltd., Sanofi, Sumitomo Dainippon Pharma Co., Ltd., Takeda Pharmaceutical Company Limited.
1971-P: SGLT1-Mediated Glucose Absorption Is Important for Incretin Hormone Secretion after Gastric Bypass Surgery
Authors: MARTINUSSEN CHRISTOFFER , VEEDFALD SIMON , BOJSEN-MOLLER KIRSTINE N. , DIRKSEN CARSTEN , SVANE MARIA S. , KRISTIANSEN VIGGO BJERREGAARD , HOLST JENS J. , MADSBAD STEN 
Published: June 2019

Postprandial GLP-1 secretion is greatly enhanced after Roux-en-Y gastric bypass (RYGB) and seems important for the reduced food intake and improved insulin secretion postoperatively. Understanding the mechanisms of gut hormone release after RYGB could aid the discovery of new drugs for the treatment of diabetes and obesity. Glucose is particularly potent for stimulating the release of GLP-1 as well as GIP compared with protein and fat in RYGB operated patients. It is unclear how glucose triggers gut hormone secretion in humans, but animal studies suggest a crucial role of sodium-glucose transporter 1 (SGLT1).
Our aim was to investigate secretion of GLP-1 and GIP in response to an oral glucose load (50 g) on two separate days with or without acute pretreatment of 600 mg of the dual SGLT1/SGLT2 inhibitor canagliflozin (CANA) in 10 RYGB operated patients with no history of diabetes (age 47 ± 5 years, BMI 36 ± 7 kg/m2, HbA1c 35 ± 4 mmol/mol, time from surgery 6 ± 1 years, mean ± SD).
CANA lowered peak glucose (11.8 vs. 8.4 mmol/l, p&lt;0.01) and tended to decrease glucose concentrations during the 4-hour test period (AUC placebo: 1453, CANA: 1343 min mmol/l, p=0.08). CANA inhibited the early rise in GLP-1 secretion with a 28% reduction in peak concentration (p=0.03, 95% CI [-46%, -2.9%]), but a prolonged secretion was seen at later timepoints and overall GLP-1 secretion was comparable (AUC above basal 6067 vs. 7273 min pmol/l, p=0.23). GIP secretion was diminished by CANA (peak by 57%, p&gt;0.01, and AUC above basal by 28%, p=0.01, respectively). In addition, CANA reduced the postprandial rise in lactate concentrations and pulse rate and caused marked glucosuria (0.2 vs. 11 g).
SGLT1/2 inhibition by canagliflozin during glucose ingestion reduced glycemic excursions and diminished early release of GLP-1 and GIP in RYGB operated patients. The results support that glucose absorption via SGLT1 is important for incretin hormone secretion after gastric bypass.

Disclosure
C. Martinussen: None. S. Veedfald: None. K.N. Bojsen-Moller: None. C. Dirksen: None. M.S. Svane: None. V. Kristiansen: None. J.J. Holst: Advisory Panel; Self; Novo Nordisk A/S. S. Madsbad: None.

Funding
European Union Horizon 2020 Research and Innovation Program (695069-Bypass Without Surgery); Danish Diabetes Academy; Novo Nordisk Foundation (NNF15OC0017188); Research Foundation for Health Research of the Capital Region of Denmark; Hvidovre Hospital
1977-P: Methylglyoxal May Contribute to Bone Loss via Differential Effects on Osteoblast and Osteoclasts
Authors: YUE KEVIN , YAN LEE FIONA CHEUK 
Published: June 2019

Purpose of the Study: Diabetes mellitus is characterized by chronic hyperglycemia and diabetic complications. Methylglyoxal (MG) is a reactive advanced glycation end-product precursor in which abnormal accumulation is found in the serum of diabetic patients. In clinical studies, they are found to have higher risk of bone fracture. Yet, the underlying mechanism has not been elucidated. Bone remodeling, depending on the interaction between osteoblast (OB) and osteoclast (OC), is to maintain bone structural integrity, such to resorb aged cells while replacing with newly formed cells and to support the metabolic function of bones. Both OB and OC were found to be severely affected by MG. Hence the effect of MG leading to subsequent bone loss was investigated.
Methods: In this study, the effects of MG on bone in both animal and cell models were investigated. SD rats were treated with MG (50mM, 10mL/kg) for 8 weeks. Proximal end of tibia were collected for analysis. The bone mineral density (BMD) and mRNA expression of bone biomarkers were measured using micro-CT and RT-PCR respectively.
Results: Using micro-CT scanning, MG-treated group has lower trabecular BMD (318.1 ± 10.9 mg HA/ccm) compared with control group (383.2 ± 17.7 mg HA/ccm). Using RT-PCR, it was found there were decreased expressions in OB biomarkers including Bone Gamma-Carboxyglutamate Protein (0.718 fold), Collagen I (0.25 fold); while increasing RANKL/OPG (9.46 fold) and Sclerostin (3.51 fold) after MG treatment, indicating the inhibition of bone formation. Besides, increased expressions in OC biomarkers Cathepsin K (1.51 fold), Osteoclast-associated receptor (1.90 fold), Receptor activator of nuclear factor kappa B (1.34 fold) and Tartrate-resistant acid phosphatase (2.57 fold) were observed indicating activation of OC.
Conclusions: MG activates OC and inhibits OB, leading to lower BMD and more porous bone architecture. Therefore, MG may contribute to the bone loss through imbalanced bone remodeling in both OC and OB.

Disclosure
K. Yue: None. F. Lee: None.
1985-P: Inhibition of Adipocyte-Derived Serotonin Protects from High-Fat Diet-Induced Obesity by Increasing Energy Expenditure
Authors: SHONG KO EUN , CHOI WONGUN , KIM HAIL 
Published: June 2019

Serotonin (5-HT) is a monoamine that has various functions in both neuronal and non-neuronal systems. 5-HT has been known as an anorexigenic neurotransmitter in central nervous system. However, accumulating evidences suggest that peripheral 5-HT may also affect organismal energy homeostasis. Here we demonstrate the role of adipocyte-derived 5-HT in the regulation of systemic energy metabolism. The expression of tryptophan hydroxylase-1 (Tph1), the rate-limiting enzyme for 5-HT synthesis, and tissue 5-HT level were increased in white adipose tissue (WAT) when mice were fed with high fat diet. Pharmacological inhibition of 5-HT synthesis using Tph inhibitor suppressed the lipogenesis in epididymal WAT, induced beige adipogenesis in inguinal WAT and activated the adaptive thermogenesis in brown adipose tissue (BAT). Adipocyte-specific Tph1 KO (Tph1 FKO) mice exhibited similar phenotypes, suggesting the localized effects of 5-HT on adipose tissues. Tph1 FKO mice showed decreased body fat mass and increased energy expenditure, resulting in improved glucose tolerance. Ucp1 expression increased in the Tph1 FKO iWAT. These data suggest important roles of adipocyte-derived 5-HT in controlling energy homeostasis.

Disclosure
K. Shong: None. W. Choi: None. H. Kim: None.
2000-P: Intracellular Metabolism-Dependent PDGF-B Induction in Inflammatory Macrophages Contributes to Adipose Tissue Expansion with Obesity
Authors: WADA TSUTOMU , ONOGI YASUHIRO , OKEKAWA AKIRA , MATSUZAWA TAKATOSHI , WATANABE ERI , KOMATSU GO , TSUNEKI HIROSHI , SASAOKA TOSHIYASU 
Published: June 2019

White adipose tissue (WAT) expands with angiogenesis. We have demonstrated that adipose-tissue-macrophages (ATMs) highly express platelet-derived growth factor (PDGF)-B in obesity, and exposure of PDGF-B stimulates detachment of pericytes (PCs) from vessels. Since vessel-attached PCs inhibit endothelial cell growth, the detachment restarts angiogenesis. In the present study, we aimed to clarify the significance of ATMs on adipose angiogenesis. Intraperitoneal injection of liposome-encapsulated clodronate (Clod) for 6 weeks achieved depletion of macrophages and decreased expression of Pdgfb mRNA in WAT of HFD-fed mice. Clod-treated mice showed smaller WAT with vessels well covered with PCs compared to control mice. We next investigated underlying mechanism of Pdgfb induction. LPS but not IL-4 stimulated Pdgfb expression in peritoneal macrophages. In RAW 264.7 macrophages, Pdgfb expression induced by high glucose plus LPS stimulation was completely blocked by pretreatment with 2-deoxyglucose (2-DG), a hexokinase inhibitor or heptelidic acid, a GAPDH inhibitor, whereas it was not affected by treatment with 6-aminonicotinamide, an inhibitor of glucose-6-phosphate dehydrogenase acting as the rate-limiting enzyme of the pentose phosphate pathway. In addition, high glucose plus LPS induced phosphorylations of S6 kinase, ERK, and JNK but not p38 MAP kinase. These phosphorylations were significantly attenuated by treatment with 2DG. Importantly, enhanced expression of Pdgfb by high glucose plus LPS was effectively suppressed by inhibitor or knockdown of Erk but not by rapamycin. The expression was also attenuated by inhibition of NFκb pathway.
In conclusion, hyperglycemia and chronic inflammation reprogram metabolic pathways toward glycolysis, and subsequent activation of NFκB plays a pivotal role in the production of PDGF-B in ATMs during obesity development.

Disclosure
T. Wada: None. Y. Onogi: None. A. Okekawa: None. T. Matsuzawa: None. E. Watanabe: None. G. Komatsu: None. H. Tsuneki: None. T. Sasaoka: None.

Funding
Japan Society for the Promotion of Science (JP18K08469)
2006-P: The Role of Adipose Tissue-Resident Eosinophils in Adipocyte Metabolism and Whole-Body Energy Homeostasis
Authors: LI TING , LESUER WILLIAM , SINGH ABHILASHA , HERNANDEZ JAMES D. , ZHANG XIAODONG , JELINEK DIANE , LIU JUN , VELLA ADRIAN , JACOBSEN ELIZABETH A. , DEFILIPPIS ELEANNA 
Published: June 2019

Adipose tissue resident eosinophils (AT-EOS) are thought to play a pivotal role in whole-body energy homeostasis. However, the precise role of, and the mechanisms underlying AT-EOS in the regulation of whole-body energy metabolism remains elusive. This is because of the limitations of rodent models which have been genetically engineered to either produce elevated whole-body eosinophils or knock-out models for this hematopoietic lineage. To determine the function of AT-EOS, we generated a transgenic mouse model overexpressing human eotaxin[AV1] 2 (hEo2), which is an eosinophil specific chemokine, under the control of a fat-specific aP2 promoter, to recruit circulating EOS exclusively into adipose (hEo2tg). Compared to wild type (WT) littermates of both genders, hEo2tg mice displayed a significant increase of AT-EOS in multiple AT depots including, perirenal and subcutaneous white adipose tissue (sWAT). However, EOS were not increased in brown adipose tissue (BAT). When fed a high-fat diet (HFD), hEo2tg mice gained less weight (males weight: 45.5 ±0.7g vs. 51 ±0.4g, P&lt;0.01 hEo2tg vs. WT) and adipose tissue (males %fat: 20.8 ±0.2 vs. 31.7 ±0.6, P&lt;0.01 hEo2tg vs. WT) compared to WT. Transgenic mice showed improved glucose tolerance (GTT) compared to WT (males GTT AUC: 300054±121 vs. 320865 ±920, hEo2tg vs. WT P&lt;0.001). This was accompanied by increased energy expenditure and heat production compared to WT. These phenotypes were equally found in female animals. Moreover, the adipocytes in hEo2tg were smaller in both genders, and the expression of genes involved in fat oxidation in BAT and sWAT was upregulated in hEo2tg mice compared to WT mice. These data suggest that WAT-resident EOS contribute to increased BAT activation, browning of sWAT and to whole-body energy expenditure. Additional studies will be needed to evaluate the molecular mechanism(s) underling the benefits of AT- EOS.

Disclosure
T. Li: None. W. LeSuer: None. A. Singh: None. J.D. Hernandez: None. X. Zhang: None. D. Jelinek: None. J. Liu: None. A. Vella: Advisory Panel; Self; vTv Therapeutics. Research Support; Self; Novo Nordisk Inc. E.A. Jacobsen: None. E. DeFilippis: None.

Funding
National Center for Advancing Translational Sciences (KL2TR002379)
2016-P: High Dose DACRA Treatment Improves Glucose Homeostasis, without Additional Weight Loss
Authors: SONNE NINA , LARSEN ANNA T. , ANDREASSEN KIM V. , KARSDAL MORTEN ASSER , HENRIKSEN KIM 
Published: June 2019

KBP is a Dual Amylin and Calcitonin Receptor Agonist (DACRA). DACRAs have shown efficacy on weight loss and glucose control in rats. However, it is unclear whether the maximum effect has been reached. High Fat Diet (HFD, 60% fat) fed male Sprague-Dawley rats entered a dose escalation regimen ending at 5 (normal dose), 50 or 500 µg/kg daily KBP (n=10/group). Male ZDF (fa/fa) rats received identical doses without dose escalation in a preventive study setup (n=9-10/group). In HFD rats, KBP treatment resulted in a transient decrease in food intake at each dose escalation step. At study end, KBP treatment resulted in a significant weight loss of 77-94 g (13-16%, P&lt;0.0001) compared to vehicle. Furthermore, KBP reduced the weight of adipose tissues (P&lt;0.05). Surprisingly, there was a trend of 5 µg/kg KBP causing a more pronounced adipose-specific weight loss compared to 500 µg/kg (subcutaneous 1.7 vs. 0.7 g, visceral 4.1 vs. 2.5 g adipose weight loss). During two OGTTs, KBP treatment significantly lowered blood glucose (BG) and insulin levels compared to vehicle indicating improved glucose tolerance. Lastly, 24h fecal energy loss increased by KBP treatment, though this trend was absent when accounting for food intake and total feces output.
In ZDF rats, KBP treatment significantly improved fasting BG (endpoint vehicle 29.5, endpoint KBP average 18.3 mmol/L, tAUC P&lt;0.0001) and HbA1c (vehicle 10.2%, KBP average 6.1%, P&lt;0.0001) compared to vehicle, with no significant difference between treatment groups. Importantly, fasting and non-fasting insulin levels of KBP-treated rats were increased compared to vehicle in a dose-dependent manner during an OGTT, resulting in lowered BG levels. Increased insulin levels suggest that KBP protects against the known β-cell degradation in the ZDF model.
Taken together, these data suggest that higher doses of KBP than previously investigated may preserve insulin secretion to a greater extent. With respect to weight loss, no additional benefit was observed from the high doses.

Disclosure
N. Sonne: None. A.T. Larsen: None. K.V. Andreassen: Employee; Self; Nordic Bioscience. M.A. Karsdal: Employee; Self; Nordic Bioscience. K. Henriksen: Employee; Self; Nordic Bioscience. Employee; Spouse/Partner; Novo Nordisk A/S. Stock/Shareholder; Self; Nordic Bioscience. Other Relationship; Self; Nordic Bioscience.
2022-P: Neonatal IL-4 Administration Decreases Body Fat Content and Weight and Improves Glucose Tolerance in Adulthood
Authors: YING TAMMY , SIMMONS REBECCA A. 
Published: June 2019

Intrauterine growth restriction (IUGR) due to uteroplacental insufficiency is a common complication of pregnancy and leads to an increased risk for type 2 diabetes (T2D) in adulthood. We model IUGR by performing bilateral uterine artery ligation in pregnant rats at d18 of gestation (term 22 days). Offspring are growth restricted and newborn males, but not females have decreased ß-cell proliferation and impaired insulin secretion which is associated with inflammation and increased IL-4 levels. IUGR males develop obesity and insulin resistance in adulthood. Neutralizing IL-4 antibody given on postnatal days 1-6 normalizes hyperglycemia in adult IUGR animals. The aim of this study was to determine whether IL-4 is sufficient to recapitulate the IUGR phenotype. IL-4 (50ng or 100ng) or PBS was injected subcutaneously to normal newborn rat pups on postnatal days 1-6. IL-4 had no adverse effects on newborn rat pups and weights did not differ between the IL-4 and PBS injected pups (n=15). IL-4 injection had no effect on insulin secretion as measured by both static incubation experiments and perifusion square wave studies (n=6). Surprisingly, at P14, animals treated with IL-4 in the newborn period had decreased body fat content (p=0.0173) compared to controls (n=6). Further, at 7 weeks of age IL-4 injected rats weighed less than controls (n=7; p=0.00017) and the weight difference increased with age. At 10 weeks, IL-4 injected rats had decreased fasting blood glucose levels (n=6-7; p=0.0055) and improved glucose tolerance and the area under the curve (AUC) was less than controls (n=3; p=0.0513). These results suggest that IL-4 is not sufficient to recapitulate the IUGR metabolic phenotype. However, IL-4 administered transiently during the neonatal period has lasting effects in adulthood, decreasing fat content and improving glucose tolerance.

Disclosure
T. Ying: None. R.A. Simmons: None.

Funding
National Institutes of Health