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P1-44 Differential effects of maternal nutrient restriction between early to mid gestation on cardiac acetyl CoA carboxylase (ACC) expression following juvenile obesity
Posters cardiac function in adult life, following catch up growth, and could contribute to the link between IUGR and heart disease at older ages. P1-44 Differential effects of maternal nutrient restriction between early to mid gestation on cardiac acetyl CoA carboxylase (ACC) expression following juvenile obesity L.L.Y. Chan1 , S. Sebert1 , H. Budge1 , T. Stephenson1 , M.E. Symonds1 *, D.S. Gardner2 . 1 Centre for Reproduction and Early Life, School of Human Development and 2 Schools of Veterinary Medicine and Science, University of Nottingham, United Kingdom E-mail: [email protected] Aims: Obesity is associated with hypertension, leading to pressure-overload left ventricular hypertrophy in conjunction with reduced energy production from fatty acid oxidation and mitochondrial dysfunction. The present study examined the extent to which maternal nutrient restriction, coincident with early heart development, may exacerbate the adverse cardiac effects of later obesity. Study design: Welsh Mountain sheep (n = 21) were either nutrientrestricted (NR; i.e. fed 50% less than controls) between earlyto-mid (30 80 days) gestation or fed a control diet throughout pregnancy. From weaning to 12 months of age, offspring were either maintained out to pasture with unrestricted physical activity (Lean, L), or group-housed within a barn in order to restrict their activity and provided with ad libitum access to hay and concentrate pellets (Obese, O; NR obese, NRO). At 12 months, the left ventricle was sampled, snap frozen and mRNA subsequently extracted for real-time PCR analysis. Results: Obesity resulted in pronounced left ventricular pressureoverload hypertrophy in conjunction with lower mRNA abundance for both PGC-1a and AMPKa2 relative to lean sheep (p < 0.05). In contrast, ACC mRNA abundance was only reduced in the O group and was, thus, similar between L and ONR groups. Conclusions: Both AMPK and ACC are involved in the metabolic switch in fatty acid oxidation. Thus, our results suggest that obesity decreases capacity of mitochondrial oxidative energy metabolism in heart. Importantly, such an adaptation may be differentially recruited in offspring born to nutrient restricted mothers, thereby altering lipid accumulation in their hearts. Study supported by the British Heart Foundation P1-45 Maternal severe undernutrition during both late gestation and lactation period induce hypertension in male rat offspring H. Takahashi *, T. Okawa, K. Fujimori, A. Sato. Department of Obstetrics and Gynecology Fukushima Medical University School of Medicine, Fukushima, Japan Objective: Exposure to undernutrition during fetal life has been proposed as an underlying cause of adult hypertension, but the effect of undernutrition during lactation period is unclear. Our objective was to investigate the effects of either severe undernutrition during late gestation or lactation period on blood pressure and the development of vascular function in male rat offspring. Study design: We use normal pregnant Wistar rats (Group A), nutritionally restricted by feeding with 30% of the normal gestationmatched dietary intake from day 17 of gestation to delivery (Group B) and 30% restricted after delivery to the end of lactation period (Group C). The offspring was measured blood pressure at 12 and 24 weeks by using indirect tail-cuff method. Rings of thoracic aorta with intact endothelium from the male offspring of A and B at 8 weeks, were equilibrated at 2 g passive tension in organ chambers filled with Krebs-Henseleit solution continuously bubbled with 5%CO2 in air (37ºC, pH 7.4) for isometric tension recording. Concentration response relationships to Norepinephrine (NE) and angiotensin II (AT II) were obtained in
S95 the absence or presence of N(omega)-nitro-L-arginine methyl ester (L-NAME) or a selective AT II type-1 receptor blocker (Valsartan). Responses to cumulative concentrations of sodium nitroprusside (SNP) and to 10 5 M oxyhemoglobin (Hb, nitric oxide scavenger) were also determined. Contractions were expressed as a percent of the reference contraction induced by potassium chloride (60 mM). Statically analysis was performed using one-way ANOVA. Results: Body weight was significantly reduced in B offspring compared to A and C in male offspring at day 1 (p < 0.01). At 12 weeks the body weight of offspring of B was no difference to catch up compared to A and C offspring. Systolic and Diastolic blood pressures were significantly elevated at both 12 and 24 weeks in offspring of B > C > A. NE concentration-dependently stimulated tension of aortic rings from in A and B offspring, which was not significantly (n = 6). Maximal contractions to NE were significantly stimulated by L-NAME in A (p < 0.05), but not B offspring. Valsartan significantly inhibited aortic contractions by NE in R (p < 0.05), but not A offspring. There was no significant difference on responses of aortic rings by AT II, SNP and Hb in A and B offspring. Conclusions: Severe under nutrition during not only late gestation but also lactation period induced hypertension in male rat offspring in adulthood. Fetal origin of adult hypertension might be vascular endothelial dysfunction. P1-46 Maternal regulation of high fat nourishment during lactation period reduce a hypertension of male offspring H. Takahashi *, T. Okawa, K. Fujimori, A. Sato. Department of Obstetrics and Gynecology Fukushima Medical University School of Medicine, Fukushima, Japan Objective: Exposure to undernutrition or high fat nourishment during fetal life has been proposed as an underlying cause of adult hypertension, but the effect of maternal feeding regulation during lactation period on blood pressure of offspring is unclear. Our objective was to investigate the effects of either high-fat diet (HFD) during gestation to lactation period or restrictive fed a HFD during lactation period on blood pressure in male rat offspring. Study design: We use 3 types pregnant Wistar rats as fed with normal nutrition (Group A), with a high fat diet (HFD) during gestation to lactation period (Group B) and with HFD nutritionally restricted by feeding with 30% of the normal lactation-matched dietary intake from the day of delivery to the end of lactation period (Group C). The male offspring was measured blood pressure at 12, 24 and 60 weeks by using indirect tail-cuff method. Statically analysis was performed using one-way ANOVA. Results: Body weight was significantly reduced in C offspring compared to A and B in male offspring at day 28 after delivery (p < 0.01). At 12 weeks old, the body weight of C offspring was no difference to catch up compared to A and B offspring. Systolic and Diastolic blood pressures were significantly elevated at all 12, 24 and 60 weeks in offspring of B > C > A (p < 0.01, vs. A). Conclusions: Under high-fat nutrition during gestation to lactation period induced hypertension in male rat offspring. Maternal high fat environment make a hypertensive offspring, but regulation of fat feeding during lactation period may reduce adulthood hypertension. P1-47 Regulation of maternal feeding during lactation period may control adulthood hypertension H. Takahashi *, T. Okawa, K. Fujimori, A. Sato. Department of Obstetrics and Gynecology Fukushima Medical University School of Medicine, Fukushima, Japan Objective: Exposure to undernutrition during fetal life has been proposed as an underlying cause of adult hypertension, but the effect of either high fat nourishment or undernutrition during lactation period on blood pressure is unclear. Our objective was to investigate the most effective maternal nourishment and feeding period for offspring induced adulthood hypertension in using highfat diet (HFD).
S95 the absence or presence of N(omega)-nitro-L-arginine methyl ester (L-NAME) or a selective AT II type-1 receptor blocker (Valsartan). Responses to cumulative concentrations of sodium nitroprusside (SNP) and to 10 5 M oxyhemoglobin (Hb, nitric oxide scavenger) were also determined. Contractions were expressed as a percent of the reference contraction induced by potassium chloride (60 mM). Statically analysis was performed using one-way ANOVA. Results: Body weight was significantly reduced in B offspring compared to A and C in male offspring at day 1 (p < 0.01). At 12 weeks the body weight of offspring of B was no difference to catch up compared to A and C offspring. Systolic and Diastolic blood pressures were significantly elevated at both 12 and 24 weeks in offspring of B > C > A. NE concentration-dependently stimulated tension of aortic rings from in A and B offspring, which was not significantly (n = 6). Maximal contractions to NE were significantly stimulated by L-NAME in A (p < 0.05), but not B offspring. Valsartan significantly inhibited aortic contractions by NE in R (p < 0.05), but not A offspring. There was no significant difference on responses of aortic rings by AT II, SNP and Hb in A and B offspring. Conclusions: Severe under nutrition during not only late gestation but also lactation period induced hypertension in male rat offspring in adulthood. Fetal origin of adult hypertension might be vascular endothelial dysfunction. P1-46 Maternal regulation of high fat nourishment during lactation period reduce a hypertension of male offspring H. Takahashi *, T. Okawa, K. Fujimori, A. Sato. Department of Obstetrics and Gynecology Fukushima Medical University School of Medicine, Fukushima, Japan Objective: Exposure to undernutrition or high fat nourishment during fetal life has been proposed as an underlying cause of adult hypertension, but the effect of maternal feeding regulation during lactation period on blood pressure of offspring is unclear. Our objective was to investigate the effects of either high-fat diet (HFD) during gestation to lactation period or restrictive fed a HFD during lactation period on blood pressure in male rat offspring. Study design: We use 3 types pregnant Wistar rats as fed with normal nutrition (Group A), with a high fat diet (HFD) during gestation to lactation period (Group B) and with HFD nutritionally restricted by feeding with 30% of the normal lactation-matched dietary intake from the day of delivery to the end of lactation period (Group C). The male offspring was measured blood pressure at 12, 24 and 60 weeks by using indirect tail-cuff method. Statically analysis was performed using one-way ANOVA. Results: Body weight was significantly reduced in C offspring compared to A and B in male offspring at day 28 after delivery (p < 0.01). At 12 weeks old, the body weight of C offspring was no difference to catch up compared to A and B offspring. Systolic and Diastolic blood pressures were significantly elevated at all 12, 24 and 60 weeks in offspring of B > C > A (p < 0.01, vs. A). Conclusions: Under high-fat nutrition during gestation to lactation period induced hypertension in male rat offspring. Maternal high fat environment make a hypertensive offspring, but regulation of fat feeding during lactation period may reduce adulthood hypertension. P1-47 Regulation of maternal feeding during lactation period may control adulthood hypertension H. Takahashi *, T. Okawa, K. Fujimori, A. Sato. Department of Obstetrics and Gynecology Fukushima Medical University School of Medicine, Fukushima, Japan Objective: Exposure to undernutrition during fetal life has been proposed as an underlying cause of adult hypertension, but the effect of either high fat nourishment or undernutrition during lactation period on blood pressure is unclear. Our objective was to investigate the most effective maternal nourishment and feeding period for offspring induced adulthood hypertension in using highfat diet (HFD).