A High Fat Diet During Rat Pregnancy or Suckling Induces
Cardiovascular Dysfunction in Adult Offspring.
Khan IY, Dekou V, Douglas G, Jensen R, Hanson MA, Poston L, Taylor PD.
Maternal and Fetal Research Unit, Division of Reproductive Health, Endocrinology and Development,
King's College London, London, United Kingdom.
Epidemiological and animal studies suggest that diet-induced epigenetic modifications in early life can
contribute to development of the metabolic syndrome in adulthood. We have previously reported
features of the metabolic syndrome in adult offspring of rats fed a diet rich in animal fat during
pregnancy and suckling. We have now performed a study to compare the relative effects of high fat
feeding during a) pregnancy and b) the suckling period in the development of these disorders. As
observed previously, 6 month old female offspring of fat-fed dams suckled by the same fat-fed dams
(OHF) demonstrated raised blood pressure, despite being fed a balanced diet from weaning. Female
offspring of fat-fed dams 'cross fostered' to dams consuming a control diet during suckling (OHF/C),
demonstrated raised blood pressure compared with controls (OC), [systolic blood pressure (SBP)
(mmHg) mean+/-SEM: OHF/C, 132.5+/-3.0, n=6, versus OC, 119.0+/-3.8, n=7, P<0.05]. Female
offspring of controls 'cross-fostered' to dams consuming the fat diet (OC/HF) were also hypertensive,
[SBP (mmHg); 131.0+/-2.5 mmHg, n=6; versus OC, P<0.05]. Endothelium-dependent relaxation
(EDR) of male and female OHF and OHF/C mesenteric small arteries was similar, and blunted
compared to OC (P<0.001). OC/HF arteries showed profoundly impaired EDR (OC/HF versus OHF,
P<0.001). OHF/C and OC/HF demonstrated hyperinsulinaemia and increased adiposity. Features of the
metabolic syndrome in adult offspring of fat-fed rats can be acquired both ante-natally and during
suckling. However exposure during pregnancy confers adaptive protection against endothelial
dysfunction induced by maternal fat-feeding during suckling.
PMID: 15308487 [PubMed - as supplied by publisher]
Programming of defective rat pancreatic beta-cell function in
offspring from mothers fed a low-protein diet during gestation and
the suckling periods.
Heywood WE, Mian N, Milla PJ, Lindley KJ.
Gastroenterology Unit, Institute of Child Health, University College London, 30 Guilford St, London
WC1N 1EH, UK. w.heywood@eastman.ucl.ac.uk
Poor fetal and infant nutrition has been linked to impaired glucose tolerance in later life. We studied
the effect of protein deficiency during gestation and the suckling period in a rat model and found that
poor nutrition 'programmes' pancreatic beta-cell GK (glucokinase; known as the glucose sensor) and
glucose-stimulated insulin secretion response in newborn, suckling and adult rat offspring. Pregnant
female rats were divided into three groups: a control group was kept on a normal protein (20%) diet,
another group was fed a low-protein (LP) (6%) diet during gestation and suckling periods (LP-G + S
group) and another was fed a LP diet during gestation then a normal protein diet during the suckling
period (LP-G group). The pulsatile glucose-stimulated insulin secretion response was acutely disrupted
and the peak insulin secretion was markedly decreased in newborn and 3-week-old offspring of the LPG + S group compared with the control group. Also, there was an altered pulsatile secretory response in
adults of the LP-G + S and 3-week-old and adult offspring of the LP-G groups compared with the
control group. GK protein levels, detected by Western blotting, were decreased in newborn and 3week-old offspring of both LP-G + S and LP-G groups compared with the control groups. The Km and
Vmax of GK were altered. The prenatal and postnatal LP diet appeared to have a permanent effect in
increasing the affinity of GK for glucose (indicated by decreased Km values) and decreasing the Vmax.
This showed that the critical period of programming of the function of GK was after birth and during
the postnatal weaning period, since the adult offspring of the LP-G + S group when fed a normal
protein diet showed no reversal in the Km values of the enzyme. Similar experiments in adult offspring
of the LP-G group showed normalization of the Km values of GK at 3 weeks of age. In conclusion,
fetal and infantile nutrition 'programmes' pancreatic beta-cell function; poor nutrition during this period
caused irreversible effects on glucose homoeostatic mechanisms in the offspring, which may
predispose the offspring to diabetes in later life.
PMID: 14982492 [PubMed - indexed for MEDLINE]
Effects of caffeine on the saturated and monounsaturated Fatty acids
of the newborn rat cerebellum.
Yazdani M, Ide K, Asadifar M, Gottschalk S, Joseph F Jr, Nakamoto T.
Department of Pediatrics, Laboratory of Perinatal Nutrition and Metabolism, Louisiana State
University Health Sciences Center, New Orleans, LA 70119, USA.
Caffeine (1,3,7-trimethylxanthine) is one of the most commonly consumed drugs in our daily life, and
its use is increasing. However, very little attention has been paid to its potential effects on early growth
and development. Because of the steady increase in breast feeding of infants and because caffeine
diffuses readily into breast milk, the present study examined if caffeine intake by newborn rats during
lactation would affect the saturated and monounsaturated fatty acids in the growing cerebellum. A total
of 10 timed pregnant rats were purchased from the breeder. At birth litters were combined, and 8 pups
were randomly assigned to each dam without regard to the sex of the pups. Dams with litters were
divided into 2 groups. Dams of group 1 received a 20% protein diet as a control, and dams of group 2
received a 20% protein diet plus caffeine (4 mg/100 g BW). Pups were killed at day 10. The
cerebellums were removed, weighed and homogenized. Gas chromatograph-mass spectrometry was
used to identify and quantify free fatty acids. Chronic caffeine exposure from birth to day 10 in pups
through the maternal milk resulted in a decrease in cerebellum weight, a significant increase in the
saturated fatty acids, and a tendency toward an increase of monounsaturated fatty acids. In addition,
there was a slight increase of some of the polyunsaturated fatty acids. However, there was no
difference in food intake of the lactating dams and weight gain of the pups between the groups. These
data indicate that early caffeine intake by the suckling pups alters the composition of fatty acids of the
cerebellum; thus, avoidance of caffeine during lactation is critical. The risks and benefits of caffeine
administration in premature infants must be carefully evaluated during this rapid period of brain
growth. Copyright 2004 S. Karger AG, Basel
PMID: 14679316 [PubMed - indexed for MEDLINE]
Circulating leptin levels in newborn rats: a significant post- natal
developmental effect, independent of dietary polyunsaturated fat
levels.
Birk RZ, Regan KS, Brannon PM.
Department of Biotechnology Engineering, The Institute of Applied Biosciences, Ben-Gurion
University. P.O. Box 653, Beer-Sheva 84105, Israel. rbirk@bgumail.bgu.ac.il
Leptin expression exhibits developmental and dietary regulation, but it is unknown whether there is an
interaction of the regulation by dietary fat and postnatal development. The purpose of this study was to
test the effect of different levels of dietary polyunsaturated fat on circulating leptin levels at different
post-natal developmental stages. Pregnant (Sprague-Dawley) rats consumed from day 15 of pregnancy
through day 9 of lactation a low fat, (11% of energy; LF) polyunsaturated safflower oil diet. From day
9 of lactation, dams and their respective pups were fed low, moderate (40% of energy; MF) or high
(67% of energy; HF) polyunsaturated safflower oil diets to full maturation (56 days). Diets were isoenergetic and iso-nitrogenous. Milk fatty acid content reflected the mothers and pups diet, with 15 to
100 fold less C10:0 and 2.6 to 3.3 fold more C18:2 in MF and HF groups compared to LF diet. In
newborn rats through post-natal day 56, levels of polyunsaturated fat in mothers' milk and
mothers/pups diet had no effect on the levels of circulating leptin. The post-natal development period
significantly affected circulating leptin levels (p < 0.001, 15 days = 56 days > 21 days > 28 days). In
summary, the developmental postnatal stage regulates leptin levels, independently of the
polyunsaturated fat levels in the diet.
PMID: 13679243 [PubMed - indexed for MEDLINE]
Fructose feeding in the suckling-weaning transition in rats: effects on
hyperlipidemia in adulthood.
Bell RC, Hoedl A, Turchinsky J.
Department of Agricultural, Food and Nutritional Science, University of Alberta, Edmonton, Alberta,
Canada. Rhonda.bell@ualberta.ca
The sucking-weaning transition is characterized by high rates of growth and development and may be a
sensitive period during which dietary intake could program metabolism to increase the risk of
cardiovascular disease and diabetes in adulthood. Intake of a high fructose (FR) diet is known to induce
hypertriglyceridemia and insulin resistance in rats when they are consuming this diet. We examined
whether a FR diet fed early in life produces detrimental changes in lipid and glucose metabolism that
persist to adulthood. Weanling rats were fed 65% FR (wt/wt), a purified control diet (CNTL) or
standard chow (CHOW) for 5 weeks. Beyond 9 weeks of age, all rats were fed CHOW. During FR
feeding, plasma triglycerides (TG) were significantly elevated in the FR group (FR = 217 +/- 20;
CNTL = 163 +/- 17; chow = 156 +/- 10). At 21 wks of age, TG's were similar in rats fed FR or CNTL
versus CHOW at weaning (p > 0.87). Hepatic fatty acid synthase (FAS) activity was elevated in FR
and CNTL groups vs. CHOW (65 +/- 7, 72 +/- 6 vs. 48 +/- 4 nmol NADPH/mg protein/min, p < 0.01).
There were no differences in indices of glucose homeostasis at 21 weeks of age. Early exposure to a
diet high in simple sugars (FR or CNTL) and/or low in fiber during the suckling-weaning transition
may contribute to modest dyslipidemia later in life. Together, changes observed in this study may
increase the risk of cardiovascular disease in adulthood.
PMID: 12715271 [PubMed - indexed for MEDLINE]
Leptin levels in rat offspring are modified by the ratio of linoleic to
alpha-linolenic acid in the maternal diet.
Korotkova M, Gabrielsson B, Lonn M, Hanson LA, Strandvik B.
Departments of Pediatrics, Research Centre for Endocrinology and Metabolism, Goteborg University,
Sweden. marina.korotkova@vgregion.se
The supply of polyunsaturated fatty acids (PUFA) is important for optimal fetal and postnatal
development. We have previously shown that leptin levels in suckling rats are reduced by maternal
PUFA deficiency. In the present study, we evaluated the effect of maternal dietary intake of (n-3) and
(n-6) PUFA on the leptin content in rat milk and serum leptin levels in suckling pups. For the last 10
days of gestation and throughout lactation, the rats were fed an isocaloric diet containing 7% linseed oil
(n-3 diet), sunflower oil (n-6 diet), or soybean oil (n-6/n-3 diet). Body weight, body length, inguinal fat
pad weight, and adipocyte size of the pups receiving the n-3 diet were significantly lower during the
whole suckling period compared with n-6/n-3 fed pups. Body and fat pad weights of the n-6 fed pups
were in between the other two groups at week one, but not different from the n-6/n-3 group at week 3.
Feeding dams the n-3 diet resulted in decreased serum leptin levels in the suckling pups compared with
pups in the n-6/n-3 group. The mean serum leptin levels of the n-6 pups were between the other two
groups but not different from either group. There were no differences in the milk leptin content
between the groups. These results show that the balance between the n-6 and n-3 PUFA in the maternal
diet rather than amount of n-6 or n-3 PUFA per se could be important for adipose tissue growth and for
maintaining adequate serum leptin levels in the offspring.
PMID: 12364559 [PubMed - indexed for MEDLINE]
Maternal dietary intake of essential fatty acids affects adipose tissue
growth and leptin mRNA expression in suckling rat pups.
Korotkova M, Gabrielsson B, Hanson LA, Strandvik B.
Departments of Pediatrics, Goteborg University, SE 41685 Goteborg, Sweden.
Marina.Korotkova@vgregion.se
We have previously shown that maternal intake of essential fatty acids during late gestation and
lactation affects the level of serum leptin in pups. The aim of the present study was to investigate the
effect of dietary essential fatty acids on leptin content in the milk of rat dams and leptin expression in
white adipose tissue of pups during the suckling period. During late gestation and throughout lactation,
rats were fed a control or an essential fatty acid-deficient (EFAD) diet. Milk of the EFAD dams
contained more saturated and less polyunsaturated fatty acids compared with the control dams. Milk
leptin levels were higher in the EFAD dams than in the control dams at 3 wk of lactation. The weight
of inguinal white adipose tissue depots and the serum leptin levels of the EFAD pups were significantly
lower than in the control pups during the whole suckling period. In addition, semiquantitative reverse
transcriptase-PCR analysis of leptin mRNA levels in inguinal white adipose tissue showed a reduction
in the EFAD pups compared with the control pups at 3 wk of age. We conclude that maternal dietary
essential fatty acid intake affects serum leptin levels in pups by regulating both the amount of adipose
tissue and the leptin mRNA expression.
PMID: 12084851 [PubMed - indexed for MEDLINE]
Effects of maternal chronic alcohol administration in the rat:
lactation performance and pup's growth.
Murillo-Fuentes L, Artillo R, Carreras O, Murillo L.
Departamento de Fisiologia y Biologia Animal, Facultad de Farmacia, Universidad de Sevilla, Spain.
A fostering/crossfostering analysis of the effects of maternal ethanol exposure on lactation performance
and offspring growth was performed. Wistar rats were kept under one of the three experimental
nutritional treatments: alcohol-treated (EG), pair-fed-treated (PFG) (as a nutritional control of alcoholassociated malnutrition), and control or normal diet (CG). Rats from the EG group were accustomed to
increased amounts of ethanol (5% during the first week to 20% in the fourth week). The 20% ethanol
level was maintained throughout three additional weeks and during gestational and lactational period.
Daily food intake, fluid consumption, body weight and gestational parameters were studied in control
(CG), pair-fed (PFG) and ethanol dams (EG). At birth, half the litters were fostered to other dams of
the same treatment (GLG) and half were cross-fostered to dams of the opposite treatment (GG, LG).
No cross-fostering analyses were performed on the pair-fed group. Offspring body weight was
controlled throughout lactation. Liver, kidney and spleen weights as well as milk consumption were
also studied at the end of lactation period. In dams, a significant reduction of body weight was
described throughout the suckling period. No ethanol detrimental effects were observed on body
weight at birth, but in spite of a normal birth weight, alcohol during lactation was responsible for a
growth deficit. Milk consumption was significantly reduced in offspring exposed to ethanol during
gestation and/or lactation. Curiously, prenatal alcohol exposure affects adversely the suckling
behaviour in pups at the time of weaning. In our study, alcohol treatment and malnutrition affects liver
and spleen weights. However, malnutrition decreases spleen weights more than alcohol treatment. In
the case of the kidney weights the alcohol decreases kidney weight more than malnutrition.
Collectively, the data from the present study show similar effects following pre/postnatal and postnatal
alcohol exposure. The findings suggest that chronic alcohol administration during gestation and/or
lactation adversely affects pup growth at weaning as indicated by its effect on milk consumption, pup
and organ weight.
PMID: 11905955 [PubMed - indexed for MEDLINE]