Omega-6:Omega-3 Fatty Acid Ratio and Total Fat Content of the Maternal Diet Alter Offspring Growth and Fat Deposition in the Rat

Omega-3 long-chain polyunsaturated fatty acids (LCPUFA) have been shown to inhibit lipogenesis and adipogenesis in adult rats. Their possible early life effects on offspring fat deposition, however, remain to be established. To investigate this, female Wistar rats (n = 6–9 per group) were fed either a 9:1 ratio of linoleic acid (LA) to alpha-linolenic acid (ALA) or a lower 1:1.5 ratio during pregnancy and lactation. Each ratio was fed at two total fat levels (18% vs. 36% fat w/w) and offspring were weaned onto standard laboratory chow. Offspring exposed to a 36% fat diet, irrespective of maternal dietary LA:ALA ratio, were lighter (male, 27 g lighter; female 19 g lighter; p < 0.0001) than those exposed to an 18% fat diet between 3 and 8 weeks of age. Offspring exposed to a low LA (18% fat) diet had higher proportions of circulating omega-3 LCPUFA and increased gonadal fat mass at 4 weeks of age (p < 0.05). Reduced Srebf1 mRNA expression of hepatic (p < 0.01), gonadal fat (p < 0.05) and retroperitoneal fat (p < 0.05) tissue was observed at 4 weeks of age in male and female offspring exposed to a 36% fat diet, and hepatic Srebf1 mRNA was also reduced in male offspring at 8 weeks of age (p < 0.05). Thus, while offspring fat deposition appeared to be sensitive to both maternal dietary LA:ALA ratio and total fat content, offspring growth and lipogenic capacity of tissues appeared to be more sensitive to maternal dietary fat content.

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The effect of maternal dietary fat content and n-6:n-3 ratio on offspring growth and hepatic gene expression in the rat

British Journal Of Nutrition ◽

10.1017/s000711452000046x ◽

2020 ◽

Vol 123 (11) ◽

pp. 1227-1238

Author(s):

Sally A. V. Draycott ◽

Grace George ◽

Matthew J. Elmes ◽

Beverly S. Muhlhausler ◽

Simon C. Langley-Evans

Keyword(s):

Gene Expression ◽

Fatty Acids ◽

Fatty Acid ◽

Fatty Acid Synthase ◽

Maternal Diet ◽

Liver Weight ◽

Fat Content ◽

Sexually Dimorphic ◽

Offspring Growth ◽

Total Fat

Abstractn-6 Fatty acids have been shown to exert pro-adipogenic effects, whereas n-3 fatty acids work in opposition. Increasing intakes of linoleic acid (LA; n-6) v. α-linolenic acid (ALA; n-3) in Western diets has led to the hypothesis that consumption of this diet during pregnancy may be contributing to adverse offspring health. This study investigated the effects of feeding a maternal dietary LA:ALA ratio similar to that of the Western diet (9:1) compared with a proposed ‘ideal’ ratio (about 1:1·5), at two total fat levels (18 v. 36 % fat, w/w), on growth and lipogenic gene expression in the offspring. Female Wistar rats were assigned to one of the four experimental groups throughout gestation and lactation. Offspring were culled at 1 and 2 weeks of age for sample collection. Offspring of dams consuming a 36 % fat diet were approximately 20 % lighter than those exposed to an 18 % fat diet (P < 0·001). Male, but not female, liver weight at 1 week was approximately 13 % heavier and had increased glycogen (P < 0·05), in offspring exposed to high LA (P < 0·01). Hepatic expression of lipogenic genes suggested an increase in lipogenesis in male offspring exposed to a 36 % fat maternal diet and in female offspring exposed to a low-LA diet, via increases in the expression of fatty acid synthase and sterol regulatory element-binding protein. Sexually dimorphic responses to altered maternal diet appeared to persist until 2 weeks of age. In conclusion, whilst maternal total fat content predominantly affected offspring growth, fatty acid ratio and total fat content had sexually dimorphic effects on offspring liver weight and composition.

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Maternal Diet Influences the Reinstatement of Cocaine-Seeking Behavior and the Expression of Melanocortin-4 Receptors in Female Offspring of Rats

Nutrients ◽

10.3390/nu12051462 ◽

2020 ◽

Vol 12 (5) ◽

pp. 1462

Author(s):

Dawid Gawliński ◽

Kinga Gawlińska ◽

Małgorzata Frankowska ◽

Małgorzata Filip

Keyword(s):

Maternal Diet ◽

Dorsal Striatum ◽

Brain Structures ◽

Female Offspring ◽

Self Administration ◽

Cocaine Seeking ◽

Seeking Behavior ◽

Pregnancy And Lactation ◽

The Impact ◽

Cocaine Reward

Recent studies have emphasized the role of the maternal diet in the development of mental disorders in offspring. Substance use disorder is a major global health and economic burden. Therefore, the search for predisposing factors for the development of this disease can contribute to reducing the health and social damage associated with addiction. In this study, we focused on the impact of the maternal diet on changes in melanocortin-4 (MC-4) receptors as well as on behavioral changes related to cocaine addiction. Rat dams consumed a high-fat diet (HFD), high-sugar diet (HSD, rich in sucrose), or mixed diet (MD) during pregnancy and lactation. Using an intravenous cocaine self-administration model, the susceptibility of female offspring to cocaine reward and cocaine-seeking propensities was evaluated. In addition, the level of MC-4 receptors in the rat brain structures related to cocaine reward and relapse was assessed. Modified maternal diets did not affect cocaine self-administration in offspring. However, the maternal HSD enhanced cocaine-seeking behavior in female offspring. In addition, we observed that the maternal HSD and MD led to increased expression of MC-4 receptors in the nucleus accumbens, while increased MC-4 receptor levels in the dorsal striatum were observed after exposure to the maternal HSD and HFD. Taken together, it can be concluded that a maternal HSD is an important factor that triggers cocaine-seeking behavior in female offspring and the expression of MC-4 receptors.

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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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The impact of exposure to cafeteria diet during pregnancy or lactation on offspring growth and adiposity before weaning

Scientific Reports ◽

10.1038/s41598-019-50448-x ◽

2019 ◽

Vol 9 (1) ◽

Cited By ~ 3

Author(s):

Grace George ◽

Sally A. V. Draycott ◽

Ronan Muir ◽

Bethan Clifford ◽

Matthew J. Elmes ◽

...

Keyword(s):

Maternal Obesity ◽

Saturated Fat ◽

Cafeteria Diet ◽

Postnatal Life ◽

Chow Diet ◽

Offspring Growth ◽

Lower Protein ◽

Pregnancy And Lactation ◽

Total Fat ◽

The Impact

Abstract Exposure to maternal obesity during early-life can have adverse consequences for offspring growth and adiposity. We aimed to assess the relative contributions of exposure to maternal obesity, induced by a highly varied cafeteria diet, during pregnancy and lactation on these measures in rat offspring prior to weaning. Female Wistar rats were fed either a control (C) or cafeteria diet (O) for 8 weeks before mating, throughout pregnancy and lactation. Offspring were cross-fostered at birth to a dam on the same (CC,OO) or alternate diet prior to birth (CO,OC). Feeding a cafeteria diet based on 40 different foods, was associated with a sustained period of elevated energy intake before birth and during lactation (up to 1.7-fold), through increased sugar, total fat and saturated fat intake, and lower protein consumption. Cafeteria fed dams sustained greater weight than animals fed a control chow diet and greater perirenal adiposity by the end of lactation. Exposure to obesity during pregnancy was associated with lower offspring birth weight and body weight in early-postnatal life. In contrast, exposure during lactation alone reduced offspring weight but increased adiposity in male CO offspring before weaning. This research highlights that exposure to maternal obesity during lactation alone can programme adiposity in a sex specific manner.

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High Maternal Omega-3 Supplementation Dysregulates Body Weight and Leptin in Newborn Male and Female Rats: Implications for Hypothalamic Developmental Programming

Nutrients ◽

10.3390/nu13010089 ◽

2020 ◽

Vol 13 (1) ◽

pp. 89

Author(s):

Soniya Xavier ◽

Jasmine Gili ◽

Peter McGowan ◽

Simin Younesi ◽

Paul F. A. Wright ◽

...

Keyword(s):

Maternal Diet ◽

Female Offspring ◽

Female Rats ◽

Omega 3 ◽

Male And Female ◽

Offspring Development ◽

Metabolic Outcomes ◽

Male And Female Rats ◽

The Impact

Maternal diet is critical for offspring development and long-term health. Here we investigated the effects of a poor maternal diet pre-conception and during pregnancy on metabolic outcomes and the developing hypothalamus in male and female offspring at birth. We hypothesised that offspring born to dams fed a diet high in fat and sugar (HFSD) peri-pregnancy will have disrupted metabolic outcomes. We also determined if these HFSD-related effects could be reversed by a shift to a healthier diet post-conception, in particular to a diet high in omega-3 polyunsaturated fatty acids (ω3 PUFAs), since ω3 PUFAs are considered essential for normal neurodevelopment. Unexpectedly, our data show that there are minimal negative effects of maternal HFSD on newborn pups. On the other hand, consumption of an ω3-replete diet during pregnancy altered several developmental parameters. As such, pups born to high-ω3-fed dams weighed less for their length, had reduced circulating leptin, and also displayed sex-specific disruption in the expression of hypothalamic neuropeptides. Collectively, our study shows that maternal intake of a diet rich in ω3 PUFAs during pregnancy may be detrimental for some metabolic developmental outcomes in the offspring. These data indicate the importance of a balanced dietary intake in pregnancy and highlight the need for further research into the impact of maternal ω3 intake on offspring development and long-term health.

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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 diet high in linoleic acid alters offspring fatty acids and cardiovascular function in a rat model

British Journal Of Nutrition ◽

10.1017/s0007114521001276 ◽

2021 ◽

pp. 1-37

Author(s):

Nirajan Shrestha ◽

Simone L Sleep ◽

Tessa J Helman ◽

Olivia J Holland ◽

James SM Cuffe ◽

...

Keyword(s):

Fatty Acids ◽

Linoleic Acid ◽

Cardiac Function ◽

Maternal Diet ◽

Cardiovascular Function ◽

Hdl Cholesterol ◽

Female Offspring ◽

Total Plasma ◽

Alpha Linolenic Acid ◽

Wistar Kyoto

Abstract Linoleic acid (LA), an essential n-6 fatty acid (FA), is critical for fetal growth and development. We investigated the effects of maternal high LA (HLA) diet on offspring cardiac development and how it relates to circulating FAs and cardiovascular function in adolescent offspring, and the ability of the postnatal diet to reverse any adverse effects. Female Wistar Kyoto rats were fed low LA (LLA; 1.44% energy from LA) or HLA (6.21% energy from LA) diets for 10 weeks before pregnancy, and during gestation/lactation. Offspring, weaned at postnatal day 25 (PN25), were fed LLA or HLA diets and euthanised at PN40 (n = 6-8). Maternal HLA diet decreased circulating total cholesterol and HDL-cholesterol in females and decreased total plasma n-3 FA in males, while maternal and postnatal HLA diets decreased total plasma n-3 FA in females. Alpha- linolenic acid (ALA) and eicosapentaenoic acid (EPA) were decreased by postnatal but not maternal HLA diets in both sexes. Maternal and postnatal HLA diets increased total plasma n-6 and LA, and a maternal HLA diet increased circulating leptin, in both male and female offspring. Maternal HLA decreased slopes of systolic and diastolic PVRs, and increased cardiac Col1a1, Col3a1, Atp2a1 and Notch1 in males. Maternal and postnatal HLA diets left-shifted the diastolic PVR in female offspring. Coronary reactivity was altered in females, with differential effects on flow repayment after 10–20 sec occlusions. In conclusion, maternal HLA diets impact lipids, fatty acids and cardiac function in offspring, with postnatal diet modifying fatty acids and cardiac function in the female offspring.

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DHA Supplementation of Obese Rats throughout Pregnancy and Lactation Modifies Milk Composition and Anxiety Behavior of Offspring

Nutrients ◽

10.3390/nu13124243 ◽

2021 ◽

Vol 13 (12) ◽

pp. 4243

Author(s):

Elena Zambrano ◽

Guadalupe L. Rodríguez-González ◽

Luis A. Reyes-Castro ◽

Claudia J. Bautista ◽

Diana C. Castro-Rodríguez ◽

...

Keyword(s):

Female Offspring ◽

Milk Composition ◽

Chain Polyunsaturated Fatty Acid ◽

Dependent Manner ◽

Maternal Weight ◽

Female Wistar Rats ◽

Pregnancy And Lactation ◽

Anxiety Behavior ◽

Total Fat ◽

Total Body

We investigated if supplementing obese mothers (MO) with docosahexaenoic acid (DHA) improves milk long-chain polyunsaturated fatty acid (LCPUFA) composition and offspring anxiety behavior. From weaning throughout pregnancy and lactation, female Wistar rats ate chow (C) or a high-fat diet (MO). One month before mating and through lactation, half the mothers received 400 mg DHA kg−1 d−1 orally (C+DHA or MO+DHA). Offspring ate C after weaning. Maternal weight, total body fat, milk hormones, and milk nutrient composition were determined. Pups’ milk nutrient intake was evaluated, and behavioral anxiety tests were conducted. MO exhibited increased weight and total fat, and higher milk corticosterone, leptin, linoleic, and arachidonic acid (AA) concentrations, and less DHA content. MO male and female offspring had higher ω-6/ ω-3 milk consumption ratios. In the elevated plus maze, female but not male MO offspring exhibited more anxiety. MO+DHA mothers exhibited lower weight, total fat, milk leptin, and AA concentrations, and enhanced milk DHA. MO+DHA offspring had a lower ω-6/ω-3 milk intake ratio and reduced anxiety vs. MO. DHA content was greater in C+DHA milk vs. C. Supplementing MO mothers with DHA improves milk composition, especially LCPUFA content and ω-6/ω-3 ratio reducing offspring anxiety in a sex-dependent manner.

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Mothers cafeteria diet induced sex-specific changes in fat content, metabolic profiles, and inflammation outcomes in rats offspring

10.21203/rs.3.rs-653347/v1 ◽

2021 ◽

Author(s):

Julia Matuszewska ◽

Tomasz Zalewski ◽

Adam Klimaszyk ◽

Kamil Ziarniak ◽

Stefan Jurga ◽

...

Keyword(s):

Diabetes Type 2 ◽

Interleukin 10 ◽

Female Offspring ◽

Fat Content ◽

Metabolic Profiles ◽

Obesity And Diabetes ◽

Tnf Α ◽

Pregnancy And Lactation ◽

High Concentrations

Abstract “Western diet” containing high concentrations of sugar and fat consumed during pregnancy contributing to development of obesity and diabetes type 2 in offspring. To mimic effects of this diet, in animals cafeteria (CAF) diet is used. We hypothesis that CAF diet given to rats before, during pregnancy and lactation differently influence fat content, metabolic and inflammation profiles in offspring. Female were exposed to CAF or control diets before pregnancy, during pregnancy and lactation. At postnatal day 25 (PND 25) body composition, fat contents were measured, blood was collected for assessment of metabolic and inflammation profiles. We have found that CAF diet leaded to sex-specific alterations in offspring. At PND25, CAF offspring had: 1) higher percentage of fat content and were lighter; 2) sex-specific differences in levels of glucose; 3) higher levels of interleukins 6 (IL-6), interleukin-10 (IL-10) and tumor necrosis factor (TNF-α); 4) sex-specific differences in concentration of IL-6 and TNF-α, with increase in CAF females; 5) higher level of IL-10 in both sex, with bigger increase in females. We concluded that maternal CAF diet affects fat content, metabolic profiles, and inflammation parameters in offspring. Above effects are sex-specific, with female offspring being more susceptible to the diet.

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Mothers’ cafeteria diet induced sex-specific changes in fat content, metabolic profiles, and inflammation outcomes in rat offspring

Scientific Reports ◽

10.1038/s41598-021-97487-x ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Julia Matuszewska ◽

Tomasz Zalewski ◽

Adam Klimaszyk ◽

Kamil Ziarniak ◽

Stefan Jurga ◽

...

Keyword(s):

Diabetes Type 2 ◽

Interleukin 10 ◽

Female Offspring ◽

Fat Content ◽

Metabolic Profiles ◽

Pronounced Increase ◽

Obesity And Diabetes ◽

Tnf Α ◽

Pregnancy And Lactation ◽

High Concentrations

Abstract“Western diet” containing high concentrations of sugar and fat consumed during pregnancy contributes to development of obesity and diabetes type 2 in offspring. To mimic effects of this diet in animals, a cafeteria (CAF) diet is used. We hypothesized that CAF diet given to rats before, and during pregnancy and lactation differently influences fat content, metabolic and inflammation profiles in offspring. Females were exposed to CAF or control diets before pregnancy, during pregnancy and lactation. At postnatal day 25 (PND 25), body composition, fat contents were measured, and blood was collected for assessment of metabolic and inflammation profiles. We have found that CAF diet lead to sex-specific alterations in offspring. At PND25, CAF offspring had: (1) higher percentage of fat content, and were lighter; (2) sex-specific differences in levels of glucose; (3) higher levels of interleukin 6 (IL-6), interleukin-10 (IL-10) and tumor necrosis factor (TNF-α); (4) sex-specific differences in concentration of IL-6 and TNF-α, with an increase in CAF females; (5) higher level of IL-10 in both sexes, with a more pronounced increase in females. We concluded that maternal CAF diet affects fat content, metabolic profiles, and inflammation parameters in offspring. Above effects are sex-specific, with female offspring being more susceptible to the diet.

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