Maternal high-fat diet programs cerebrovascular remodeling in adult rat offspring

Maternal environmental factors such as diet have consequences on later health of the offspring. We found that maternal high-fat diet (HFD) exposure renders adult offspring brain more susceptible to ischemic injury. The present study was further to investigate whether HFD consumption during rat pregnancy and lactation influences the cerebral vasculature in adult male offspring. Besides the endothelial damage observed in the transmission electron microscopy, the MCAs of offspring from fat-fed dams fed with control diet (HFD/C) also displayed increased wall thickness and media/lumen ratio, suggesting that cerebrovascular hypertrophy or hyperplasia occurs. Moreover, smaller lumen diameter and elevated myogenic tone of the MCAs over a range of intralumenal pressures indicate inward cerebrovascular remodeling in HFD/C rats, with a concomitant increase in vessel stiffness. More importantly, both wire and pressure myography demonstrated that maternal HFD intake also enhanced the MCAs contractility to ET-1, accompanied by increases in ET types A receptor (ETAR) but not B (ETBR) density in the arteries. Furthermore, ETAR antagonism but not ETBR antagonism restored maternal HFD-induced cerebrovascular dysfunction in adult offspring. Taken together, maternal diet can substantially influence adult offspring cerebrovascular health, through remodeling of both structure and function, at least partially in an ET-1 manner.

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Relationship of maternal high-fat diet during pregnancy and lactation to offspring health

Nutrition Reviews ◽

10.1093/nutrit/nuaa020 ◽

2020 ◽

Cited By ~ 1

Author(s):

Kinga Gawlińska ◽

Dawid Gawliński ◽

Małgorzata Filip ◽

Edmund Przegaliński

Keyword(s):

High Fat Diet ◽

Maternal Nutrition ◽

System Development ◽

Maternal Diet ◽

Nervous System Development ◽

High Fat ◽

Preclinical Research ◽

Intrauterine Development ◽

Increased Risk ◽

Pregnancy And Lactation

Abstract A balanced maternal diet is essential for proper fetal development, and the consumption of a nutritionally inadequate diet during intrauterine development and early childhood is associated with a significantly increased risk of metabolic and brain disorders in offspring. The current literature indicates that maternal exposure to a high-fat diet exerts an irreversible influence on the general health of the offspring. This review of preclinical research examines the relationship between a maternal high-fat diet during pregnancy or lactation and metabolic changes, molecular alterations in the brain, and behavioral disorders in offspring. Animal models indicate that offspring exposed to a maternal high-fat diet during pregnancy and lactation manifest increased depressive-like and aggressive behaviors, reduced cognitive development, and symptoms of metabolic syndrome. Recently, epigenetic and molecular studies have shown that maternal nutrition during pregnancy and the suckling period modifies the development of neurotransmitter circuits and many other factors important to central nervous system development. This finding confirms the importance of a balanced maternal diet for the health of offspring.

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Maternal high-fat diet during pregnancy and lactation reduces the appetitive behavioral component in female offspring tested in a brief-access taste procedure

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.00419.2013 ◽

2014 ◽

Vol 306 (7) ◽

pp. R499-R509 ◽

Cited By ~ 14

Author(s):

Yada Treesukosol ◽

Bo Sun ◽

Alexander A. Moghadam ◽

Nu-Chu Liang ◽

Kellie L. Tamashiro ◽

...

Keyword(s):

Opioid Receptor ◽

High Fat Diet ◽

Corn Oil ◽

Sucrose Concentration ◽

Maternal Diet ◽

Female Offspring ◽

Chow Diet ◽

High Fat ◽

Endogenous Opioid ◽

Pregnancy And Lactation

Maternal high-fat diet appears to disrupt several energy balance mechanisms in offspring. Here, female offspring from dams fed a high-fat diet (HF) did not significantly differ in body weight compared with those fed chow (CHOW), when weaned onto chow diet. Yet when presented with both a chow and a high-fat diet, high-fat intake was significantly higher in HF compared with CHOW offspring. To assess taste-based responsiveness, offspring (12 wk old) were tested in 30-min sessions (10-s trials) to a sucrose concentration series in a brief-access taste test. Compared with CHOW, the HF offspring initiated significantly fewer trials but did not significantly differ in the amount of concentration-dependent licking. Thus, rather than affect lick response (consummatory), maternal diet affects spout approach (appetitive), which may be attributed to motivation-related mechanisms. Consistent with this possibility, naltrexone, an opioid receptor antagonist, further reduced trial initiation, but not licking in both groups. With naltrexone administration, the group difference in trial initiation was no longer evident, suggesting differences in endogenous opioid activity between the two groups. Relative expression of μ-opioid receptor in the ventral tegmental area was significantly lower in HF rats. When trial initiation was not required in one-bottle intake tests, no main effect of maternal diet on the intake of sucrose and corn oil emulsions was observed. Thus, the maternal high-fat diet-induced difference in diet preference is not likely due to changes in the sensory orosensory component of the taste stimulus but may depend on alterations in satiety signals or absorptive mechanisms.

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Differential Effects of Maternal High Fat Diet During Pregnancy and Lactation on Taste Preferences in Rats

Nutrients ◽

10.3390/nu12113553 ◽

2020 ◽

Vol 12 (11) ◽

pp. 3553

Author(s):

Gabor C. Mezei ◽

Serdar H. Ural ◽

Andras Hajnal

Keyword(s):

High Fat Diet ◽

Metabolic Disorders ◽

Taste Preference ◽

Normal Diet ◽

Taste Preferences ◽

Adult Offspring ◽

High Fat ◽

Preference Testing ◽

Pregnancy And Lactation ◽

The Impact

Maternal intake of high fat diet (HFD) increases risk for obesity and metabolic disorders in offspring. Developmental programming of taste preference is a potential mechanism by which this occurs. Whether maternal HFD during pregnancy, lactation, or both, imposes greater risks for altered taste preferences in adult offspring remains a question, and in turn, was investigated in the present study. Four groups of offspring were generated based on maternal HFD access: (1) HFD during pregnancy and lactation (HFD); (2) HFD during pregnancy (HFD-pregnancy); (3) HFD during lactation (HFD-lactation); and (4) normal diet (ND) during pregnancy and lactation (ND). Adult offspring 70 days of age underwent sensory and motivational taste preference testing with various concentrations of sucrose and Intralipid solutions using brief-access automated gustometers (Davis-rigs) and 24 h two-bottle choice tests, respectively. To control for post-gestational diet effects, offspring in all experimental groups were weaned on ND, and did not differ in body weight or glucose tolerance at the time of testing. Offspring exposed to maternal HFD showed increased sensory taste responses for 0.3, 0.6, 1.2 M sucrose solutions in HFD and 0.6 M in HFD-pregnancy groups, compared to animals exposed to ND. Similar effects were noted for lower concentrations of Intralipid in HFD (0.05, 0.10%) and HFD-pregnancy (0.05, 0.10, 0.5%) groups. The HFD-lactation group showed an opposite, diminished responsiveness for sucrose at the highest concentrations (0.9, 1.2, 1.5 M), but not for Intralipid, compared to ND animals. Extended-access two-bottle tests did not reveal major difference across the groups. Our study shows that maternal HFD during pregnancy and lactation has markedly different effects on preferences for palatable sweet and fatty solutions in adult offspring and suggests that such developmental programing may primarily affect gustatory mechanisms. Future studies are warranted for determining the impact of taste changes on development of obesity and metabolic disorders in a “real” food environment with food choices available, as well as to identify specific underlying mechanisms.

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Maternal High-Fat Diet Exposure During Gestation and Lactation Affects Intestinal Development in Suckling Rats

Frontiers in Physiology ◽

10.3389/fphys.2021.693150 ◽

2021 ◽

Vol 12 ◽

Author(s):

Monika Słupecka-Ziemilska ◽

Paulina Grzesiak ◽

Paweł Kowalczyk ◽

Piotr Wychowański ◽

Jarosław Woliński

Keyword(s):

High Fat Diet ◽

Metabolic Diseases ◽

Maternal Diet ◽

Dependent Manner ◽

Intestinal Development ◽

High Fat ◽

Rat Pups ◽

Diet Induced Obesity ◽

Cholinergic Signaling ◽

And Function

Maternal health and diet influence metabolic status and play a crucial role in the development of metabolic function in offspring and their susceptibility to metabolic diseases in adulthood. The pathogenesis of various metabolic disorders is often associated with impairment in intestinal structure and function. Thus, the aim of the current study was to determine the effects of maternal exposure to a high fat diet (HFD), during gestation and lactation, on small intestinal growth and maturation in rat pups at 21 days old. Female, Wistar Han rats were fed either a breeding diet (BD) or high fat diet (HFD), from mating until the 21st day of lactation. Maternal HFD exposure increased body weight, BMI and adiposity. Compared to the maternal BD, HFD exposure influenced small intestine histomorphometry in a segment-dependent manner, changed the activity of brush border enzymes and had an impact on intestinal contractility via changes in cholinergic signaling. Moreover, offspring from the maternal HFD group had upregulated mRNA expression of cyclooxygenase (COX)-2, which plays a role in the inflammatory process. These results suggest that maternal HFD exposure, during gestation and lactation, programs the intestinal development of the offspring in a direction toward obesity as observed changes are also commonly reported in models of diet-induced obesity. The results also highlight the importance of maternal diet preferences in the process of developmental programming of metabolic diseases.

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Sex Differences in Long-term Metabolic Effects of Maternal Resveratrol Intake in Adult Rat Offspring

Endocrinology ◽

10.1210/endocr/bqaa090 ◽

2020 ◽

Vol 161 (8) ◽

Cited By ~ 1

Author(s):

Purificación Ros ◽

Francisca Díaz ◽

Alejandra Freire-Regatillo ◽

Pilar Argente-Arizón ◽

Vicente Barrios ◽

...

Keyword(s):

Metabolic Disease ◽

Maternal Nutrition ◽

Maternal Diet ◽

Female Offspring ◽

Metabolic Effects ◽

Adult Offspring ◽

Adult Rat ◽

Low Fat Diet ◽

Wide Range ◽

Pregnancy And Lactation

Abstract Maternal nutrition can affect the susceptibility of the offspring to metabolic disease later in life, suggesting that this period is a window of opportunity for intervention to reduce the risk of metabolic disease. Resveratrol, a natural polyphenol, has a wide range of beneficial properties including anti-obesogenic, anti-atherosclerotic, and anti-diabetic effects. We previously reported that maternal resveratrol intake during pregnancy and lactation has early metabolic effects in the offspring with these effects at weaning depending on the type of diet ingested by the mother and the offspring’s sex. Here we analyzed whether these metabolic changes are maintained in the adult offspring and if they remain sex and maternal diet dependent. Wistar rats received a low-fat diet (LFD; 10.2% Kcal from fat) or high fat diet (HFD; 61.6% Kcal from fat) during pregnancy and lactation. Half of each group received resveratrol in their drinking water (50 mg/L). Offspring were weaned onto standard chow on postnatal day 21. Maternal resveratrol reduced serum cholesterol levels in all adult offspring from HFD mothers and increased it in adult female offspring from LFD mothers. Resveratrol increased visceral adipose tissue (VAT) in LFD offspring in both sexes but decreased it in male HFD offspring. Resveratrol shifted the distribution of VAT adipocyte size to a significantly higher incidence of large adipocytes, regardless of sex or maternal diet. These results clearly demonstrate that maternal resveratrol intake has long-lasting effects on metabolic health of offspring in a sex specific manner with these effects being highly dependent on the maternal diet.

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Maternal high fat diet during pregnancy and lactation alters hepatic expression of insulin like growth factor-2 and key microRNAs in the adult offspring

BMC Genomics ◽

10.1186/1471-2164-10-478 ◽

2009 ◽

Vol 10 (1) ◽

pp. 478 ◽

Cited By ~ 137

Author(s):

Junlong Zhang ◽

Fang Zhang ◽

Xavier Didelot ◽

Kimberley D Bruce ◽

Felino R Cagampang ◽

...

Keyword(s):

Growth Factor ◽

High Fat Diet ◽

Adult Offspring ◽

Insulin Like Growth Factor ◽

High Fat ◽

Hepatic Expression ◽

Pregnancy And Lactation

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Perinatal exposure to a high-fat diet alters proopiomelanocortin, neuropeptide Y and dopaminergic receptors gene expression and the food preference in offspring adult rats

Brazilian Journal of Biology ◽

10.1590/1519-6984.234855 ◽

2022 ◽

Vol 82 ◽

Author(s):

L. S. Santos ◽

R. J. B. Matos ◽

G. S. Cordeiro ◽

G. S. Perez ◽

D. A. E. Santo ◽

...

Keyword(s):

Gene Expression ◽

High Fat Diet ◽

Food Preference ◽

Control Diet ◽

Female Rats ◽

Dopaminergic Receptors ◽

High Fat ◽

Adult Rats ◽

Genes Expression ◽

Pregnancy And Lactation

Abstract Exposure to the hight-fat diet may alter the control of food intake promoting hyperphagia and obesity. The objective of this study was to investigate the effects of this diet on dopamine receptors (drd1 and drd2), proopiomelanocortin (pomc), neuropeptideY (npy) genes expression, and preference food in adult rats. Wistar female rats were fed a hight-fat or control diet during pregnancy and lactation. The offspring were allocated into groups: Lactation – Control (C) and High-fat (H). Post-weaning – Control Control (CC), offspring of mothers C, fed a control diet after weaning; Control Hight-fat (CH), offspring of mothers C, fed a hight-fat diet after weaning; Hight-fat Control (HC), offspring of mothers H, fed with control diet after weaning; and Hight-fat Hight-fat (HH), offspring of mothers H, fed a H diet after weaning. The groups CH and HH presented greater expression of drd1 in comparison to the CC. The drd2 of CH and HC presented higher gene expression than did CC. HH presented higher pomc expression in comparison to the other groups. HC also presented greater expression in comparison to CH. The npy of HH presented greater expression in relation to CH and HC. HH and HC have had a higher preference for a high-fat diet at 102º life’s day. The high-fat diet altered the gene expression of the drd1, drd2, pomc and npy, and influencing the food preference for high-fat diet.

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A Maternal High Fat Diet Leads to Sex-Specific Programming of Mechanical Properties in Supraspinatus Tendons of Adult Rat Offspring

Frontiers in Nutrition ◽

10.3389/fnut.2021.729427 ◽

2021 ◽

Vol 8 ◽

Author(s):

Scott M. Bolam ◽

Vidit V. Satokar ◽

Subhajit Konar ◽

Brendan Coleman ◽

Andrew Paul Monk ◽

...

Keyword(s):

Gene Expression ◽

High Fat Diet ◽

Maternal Diet ◽

Biomechanical Properties ◽

Female Offspring ◽

Male Offspring ◽

Chow Diet ◽

Adult Offspring ◽

High Fat ◽

The Impact

Background: Over half of women of reproductive age are now overweight or obese. The impact of maternal high-fat diet (HFD) is emerging as an important factor in the development and health of musculoskeletal tissues in offspring, however there is a paucity of evidence examining its effects on tendon. Alterations in the early life environment during critical periods of tendon growth therefore have the potential to influence tendon health that cross the lifespan. We hypothesised that a maternal HFD would alter biomechanical, morphological and gene expression profiles of adult offspring rotator cuff tendon.Materials and Methods: Female Sprague-Dawley rats were randomly assigned to either: control diet (CD; 10% kcal or 43 mg/g from fat) or HFD (45% kcal or 235 mg/g from fat) 14 days prior to mating and throughout pregnancy and lactation. Eight female and male offspring from each maternal diet group were weaned onto a standard chow diet and then culled at postnatal day 100 for tissue collection. Supraspinatus tendons were used for mechanical testing and histological assessment (cellularity, fibre organisation, nuclei shape) and tail tendons were collected for gene expression analysis.Results: A maternal HFD increased the elasticity (Young's Modulus) in the supraspinatus tendon of male offspring. Female offspring tendon biomechanical properties were not affected by maternal HFD. Gene expression of SCX and COL1A1 were reduced in male and female offspring of maternal HFD, respectively. Despite this, tendon histological organisation were similar between maternal diet groups in both sexes.Conclusion: An obesogenic diet during pregnancy increased tendon elasticity in male, but not female, offspring. This is the first study to demonstrate that maternal diet can modulate the biomechanical properties of offspring tendon. A maternal HFD may be an important factor in regulating adult offspring tendon homeostasis that may predispose offspring to developing tendinopathies and adverse tendon outcomes in later life.

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Leptin and Melanocortin Signaling Mediates Hypertension in Offspring From Female Rabbits Fed a High-Fat Diet During Gestation and Lactation

Frontiers in Physiology ◽

10.3389/fphys.2021.693157 ◽

2021 ◽

Vol 12 ◽

Author(s):

Kyungjoon Lim ◽

Sandra L. Burke ◽

Francine Z. Marques ◽

Kristy L. Jackson ◽

Cindy Gueguen ◽

...

Keyword(s):

Receptor Antagonist ◽

High Fat Diet ◽

Leptin Receptor ◽

Control Diet ◽

Ventromedial Hypothalamus ◽

Melanocortin Receptor ◽

Residual Body ◽

Adult Offspring ◽

High Fat ◽

Melanocyte Stimulating Hormone

Maternal high-fat diet in rabbits leads to hypertension and elevated renal sympathetic nerve activity (RSNA) in adult offspring but whether this is due to adiposity or maternal programming is unclear. We gave intracerebroventricular (ICV) and ventromedial hypothalamus (VMH) administration of leptin-receptor antagonist, α-melanocyte-stimulating hormone (αMSH), melanocortin-receptor antagonist (SHU9119), or insulin-receptor (InsR) antagonist to conscious adult offspring from mothers fed a high-fat diet (mHFD), control diet (mCD), or mCD offspring fed HFD for 10d (mCD10d, to deposit equivalent fat but not during development). mHFD and mCD10d rabbits had higher mean arterial pressure (MAP, +6.4 mmHg, +12.1 mmHg, p < 0.001) and RSNA (+2.3 nu, +3.2 nu, p < 0.01) than mCD, but all had similar plasma leptin. VMH leptin-receptor antagonist reduced MAP (−8.0 ± 3.0 mmHg, p < 0.001) in mCD10d but not in mHFD or mCD group. Intracerebroventricular leptin-receptor antagonist reduced MAP only in mHFD rabbits (p < 0.05). Intracerebroventricular SHU9119 reduced MAP and RSNA in mHFD but only reduced MAP in the mCD10d group. VMH αMSH increased RSNA (+85%, p < 0.001) in mHFD rabbits but ICV αMSH increased RSNA in both mHFD and mCD10d rabbits (+45%, +51%, respectively, p < 0.001). The InsR antagonist had no effect by either route on MAP or RSNA. Hypothalamic leptin receptor and brain-derived neurotrophic factor (BDNF) mRNA were greater in mHFD compared with mCD rabbits and mCD10d rabbits. In conclusion, the higher MAP in mHFD and mCD10d offspring was likely due to greater central leptin signaling at distinct sites within the hypothalamus while enhanced melanocortin contribution was common to both groups suggesting that residual body fat was mainly responsible. However, the effects of SHU9119 and αMSH on RSNA pathways only in mHFD suggest a maternal HFD may program sympatho-excitatory capacity in these offspring and that this may involve increased leptin receptor and BDNF expression.

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Alteration of the Early Development Environment by Maternal Diet and the Occurrence of Autistic-like Phenotypes in Rat Offspring

International Journal of Molecular Sciences ◽

10.3390/ijms22189662 ◽

2021 ◽

Vol 22 (18) ◽

pp. 9662

Author(s):

Kinga Gawlińska ◽

Dawid Gawliński ◽

Ewelina Kowal-Wiśniewska ◽

Małgorzata Jarmuż-Szymczak ◽

Małgorzata Filip

Keyword(s):

High Fat Diet ◽

Maternal Obesity ◽

Maternal Diet ◽

Repetitive Behavior ◽

Autism Spectrum ◽

High Fat ◽

Development Environment ◽

Rat Offspring ◽

Adolescent Offspring ◽

Pregnancy And Lactation

Epidemiological and preclinical studies suggest that maternal obesity increases the risk of autism spectrum disorder (ASD) in offspring. Here, we assessed the effects of exposure to modified maternal diets limited to pregnancy and lactation on brain development and behavior in rat offspring of both sexes. Among the studied diets, a maternal high-fat diet (HFD) disturbed the expression of ASD-related genes (Cacna1d, Nlgn3, and Shank1) and proteins (SHANK1 and TAOK2) in the prefrontal cortex of male offspring during adolescence. In addition, a maternal high-fat diet induced epigenetic changes by increasing cortical global DNA methylation and the expression of miR-423 and miR-494. As well as the molecular changes, behavioral studies have shown male-specific disturbances in social interaction and an increase in repetitive behavior during adolescence. Most of the observed changes disappeared in adulthood. In conclusion, we demonstrated the contribution of a maternal HFD to the predisposition to an ASD-like phenotype in male adolescent offspring, while a protective effect occurred in females.

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