Posters S95
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. 1Centre for Reproduction and
Early Life, School of Human Development and 2Schools 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 nutrient-
restricted (NR; i.e. fed 50% less than controls) between early-
to-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 pressure-
overload 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 gestation-
matched 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
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 5M 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 high-
fat diet (HFD).
