scholarly journals Maternal Diet-induced Obesity Programs Cardiovascular Dysfunction in Adult Male Mouse Offspring Independent of Current Body Weight

Endocrinology ◽  
2014 ◽  
Vol 155 (10) ◽  
pp. 3970-3980 ◽  
Author(s):  
Heather L. Blackmore ◽  
Youguo Niu ◽  
Denise S. Fernandez-Twinn ◽  
Jane L. Tarry-Adkins ◽  
Dino A. Giussani ◽  
...  
Keyword(s):  
Body Weight ◽  
Maternal Obesity ◽  
Maternal Diet ◽  
Saturated Fat ◽  
Premature Death ◽  
Causal Link ◽  
Cardiac Contraction ◽  
Diet Induced Obesity ◽  
Increased Risk ◽  
Pregnancy And Lactation

Abstract Obese pregnancies are not only associated with adverse consequences for the mother but also the long-term health of her child. Human studies have shown that individuals from obese mothers are at increased risk of premature death from cardiovascular disease (CVD), but are unable to define causality. This study aimed to determine causality using a mouse model of maternal diet–induced obesity. Obesity was induced in female C57BL/6 mice by feeding a diet rich in simple sugars and saturated fat 6 weeks prior to pregnancy and throughout pregnancy and lactation. Control females were fed laboratory chow. Male offspring from both groups were weaned onto chow and studied at 3, 5, 8, and 12 weeks of age for gross cardiac morphometry using stereology, cardiomyocyte cell area by histology, and cardiac fetal gene expression using qRT-PCR. Cardiac function was assessed by isolated Langendorff technology at 12 weeks of age and hearts were analyzed at the protein level for the expression of the β1 adrenergic receptor, muscarinic type-2 acetylcholine receptor, and proteins involved in cardiac contraction. Offspring from obese mothers develop pathologic cardiac hypertrophy associated with re-expression of cardiac fetal genes. By young adulthood these offspring developed severe systolic and diastolic dysfunction and cardiac sympathetic dominance. Importantly, cardiac dysfunction occurred in the absence of any change in corresponding body weight and despite the offspring eating a healthy low-fat diet. These findings provide a causal link to explain human observations relating maternal obesity with premature death from CVD in her offspring.

scholarly journals Effects of maternal diet-induced obesity on metabolic disorders and age-associated miRNA expression in the liver of male mouse offspring

2021 ◽  
Author(s):  
Laís Vales Mennitti ◽  
Asha A. M. Carpenter ◽  
Elena Loche ◽  
Lucas C. Pantaleão ◽  
Denise S. Fernandez-Twinn ◽  
...  
Keyword(s):  
Body Weight ◽  
Lipid Content ◽  
Metabolic Disorders ◽  
Maternal Obesity ◽  
Maternal Diet ◽  
Whole Body ◽  
Mrna Levels ◽  
Hepatic Lipid ◽  
Diet Induced Obesity ◽  
Hepatic Lipid Content

Abstract Objective This study investigated the effect of maternal obesity on aged-male offspring liver phenotype and hepatic expression of a programmed miRNA. Methods A mouse model (C57BL/6 J) of maternal diet-induced obesity was used to investigate fasting-serum metabolites, hepatic lipid content, steatosis, and relative mRNA levels (RT-PCR) and protein expression (Western blotting) of key components involved in hepatic and mitochondrial metabolism in 12-month-old offspring. We also measured hepatic lipid peroxidation, mitochondrial content, fibrosis stage, and apoptosis in the offspring. To investigate potential mechanisms leading to the observed phenotype, we also measured the expression of miR-582 (a miRNA previously implicated in liver cirrhosis) in 8-week-old and 12-month-old offspring. Results Body weight and composition was similar between 8-week-old offspring, however, 12-month-old offspring from obese mothers had increased body weight and fat mass (19.5 ± 0.8 g versus 10.4 ± 0.9 g, p < 0.001), as well as elevated serum levels of LDL and leptin and hepatic lipid content (21.4 ± 2.1 g versus 12.9 ± 1.8 g, p < 0.01). This was accompanied by steatosis, increased Bax/Bcl-2 ratio, and overexpression of p-SAPK/JNK, Tgfβ1, Map3k14, and Col1a1 in the liver. Decreased levels of Bcl-2, p-AMPKα, total AMPKα and mitochondrial complexes were also observed. Maternal obesity was associated with increased hepatic miR-582-3p (p < 0.001) and miR-582-5p (p < 0.05). Age was also associated with an increase in both miR-582-3p and miR-582-5p, however, this was more pronounced in the offspring of obese dams, such that differences were greater in 12-month-old animals (−3p: 7.34 ± 1.35 versus 1.39 ± 0.50, p < 0.0001 and −5p: 4.66 ± 1.16 versus 1.63 ± 0.65, p < 0.05). Conclusion Our findings demonstrate that maternal diet-induced obesity has detrimental effects on offspring body composition as well as hepatic phenotype that may be indicative of accelerated-ageing phenotype. These whole-body and cellular phenotypes were associated with age-dependent changes in expression of miRNA-582 that might contribute mechanistically to the development of metabolic disorders in the older progeny.

scholarly journals Obesity during pregnancy results in maternal intestinal inflammation, placental hypoxia, and alters fetal glucose metabolism at mid-gestation

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Jessica G. Wallace ◽  
Christian J. Bellissimo ◽  
Erica Yeo ◽  
Yu Fei Xia ◽  
Jim J. Petrik ◽  
...  
Keyword(s):  
Structural Changes ◽  
Maternal Obesity ◽  
Intestinal Inflammation ◽  
Maternal Diet ◽  
Cell Number ◽  
Amino Acid Transporters ◽  
Metabolic Dysfunction ◽  
Transcript Levels ◽  
Increased Risk ◽  
Placental Inflammation

AbstractWe investigated whether diet-induced changes in the maternal intestinal microbiota were associated with changes in bacterial metabolites and their receptors, intestinal inflammation, and placental inflammation at mid-gestation (E14.5) in female mice fed a control (17% kcal fat, n = 7) or a high-fat diet (HFD 60% kcal fat, n = 9; ad libitum) before and during pregnancy. Maternal diet-induced obesity (mDIO) resulted in a reduction in maternal fecal short-chain fatty acid producing Lachnospiraceae, lower cecal butyrate, intestinal antimicrobial peptide levels, and intestinal SCFA receptor Ffar3, Ffar2 and Hcar2 transcript levels. mDIO increased maternal intestinal pro-inflammatory NFκB activity, colonic CD3+ T cell number, and placental inflammation. Maternal obesity was associated with placental hypoxia, increased angiogenesis, and increased transcript levels of glucose and amino acid transporters. Maternal and fetal markers of gluconeogenic capacity were decreased in pregnancies complicated by obesity. We show that mDIO impairs bacterial metabolite signaling pathways in the mother at mid-gestation, which was associated with significant structural changes in placental blood vessels, likely as a result of placental hypoxia. It is likely that maternal intestinal changes contribute to adverse maternal and placental adaptations that, via alterations in fetal hepatic glucose handling, may impart increased risk of metabolic dysfunction in offspring.

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

2020 ◽  
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.

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

2019 ◽  
Vol 9 (1) ◽  
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.

scholarly journals Bitter Melon (Momordica charantia L.) Supplementation Has No Effect on Hypercholesterolemia and Atherosclerosis in Mice

2020 ◽  
Vol 4 (10) ◽  
Author(s):  
Shayan Mohammadmoradi ◽  
Deborah A Howatt ◽  
Hong S Lu ◽  
Alan Daugherty ◽  
Sibu P Saha
Keyword(s):  
Body Weight ◽  
Plasma Cholesterol ◽  
Ldl Receptor ◽  
Saturated Fat ◽  
Momordica Charantia ◽  
Cholesterol Concentration ◽  
Bitter Melon ◽  
Diet Induced Obesity ◽  
Atherosclerosis Development ◽  
Deficient Mice

ABSTRACT Bitter melon (BM; Momordica charantia L.) has been reported to ameliorate diet-induced obesity and dyslipidemia. However, the effects of BM on atherosclerosis have not been determined. This study investigated the effects of BM diet-induced atherosclerosis in LDL receptor–deficient mice. A total of 30 female mice (aged 6–8 wk) were fed a saturated fat–enriched diet. In group 1 (n = 10), mice were fed this diet alone, whereas mice in groups 2 and 3 (n = 10/group) were fed the diet supplemented with BM either 0.1% or 1% by weight. After 12 wk, body weight, plasma cholesterol, and atherosclerotic plaque areas were analyzed. No significant differences in body weight and plasma cholesterol concentrations were observed among the groups. Also, BM supplementation did not affect atherosclerosis development. In conclusion, dietary BM has no effect on plasma cholesterol concentration and atherogenesis in hypercholesterolemic mice.

scholarly journals Body weight homeostat that regulates fat mass independently of leptin in rats and mice

2017 ◽  
Vol 115 (2) ◽  
pp. 427-432 ◽  
Author(s):  
John-Olov Jansson ◽  
Vilborg Palsdottir ◽  
Daniel A. Hägg ◽  
Erik Schéle ◽  
Suzanne L. Dickson ◽  
...  
Keyword(s):  
Body Weight ◽  
Fat Mass ◽  
Weight Bearing ◽  
The Body ◽  
Bone Strain ◽  
Body Fat Mass ◽  
Feedback Systems ◽  
Diet Induced Obesity ◽  
Increased Risk ◽  
Rats And Mice

Subjects spending much time sitting have increased risk of obesity but the mechanism for the antiobesity effect of standing is unknown. We hypothesized that there is a homeostatic regulation of body weight. We demonstrate that increased loading of rodents, achieved using capsules with different weights implanted in the abdomen or s.c. on the back, reversibly decreases the biological body weight via reduced food intake. Importantly, loading relieves diet-induced obesity and improves glucose tolerance. The identified homeostat for body weight regulates body fat mass independently of fat-derived leptin, revealing two independent negative feedback systems for fat mass regulation. It is known that osteocytes can sense changes in bone strain. In this study, the body weight-reducing effect of increased loading was lost in mice depleted of osteocytes. We propose that increased body weight activates a sensor dependent on osteocytes of the weight-bearing bones. This induces an afferent signal, which reduces body weight. These findings demonstrate a leptin-independent body weight homeostat (“gravitostat”) that regulates fat mass.

Maternal and postweaning diet interaction alters hypothalamic gene expression and modulates response to a high-fat diet in male offspring

2009 ◽  
Vol 297 (4) ◽  
pp. R1049-R1057 ◽  
Author(s):  
Kathleen C. Page ◽  
Raleigh E. Malik ◽  
Joshua A. Ripple ◽  
Endla K. Anday
Keyword(s):  
Body Weight ◽  
High Fat Diet ◽  
Saturated Fat ◽  
Male Offspring ◽  
Regulatory Subunit ◽  
Cytokine Signaling ◽  
Chow Diet ◽  
Metabolic Dysfunction ◽  
High Fat ◽  
Pregnancy And Lactation

Epidemiological data and results from animal studies indicate that imbalances in maternal nutrition impact the expression of metabolic disorders in the offspring. We tested the hypothesis that consumption of excess saturated fats during pregnancy and lactation contributes to adult metabolic dysfunction and that these disturbances can be further influenced by the postweaning diet. Adult male offspring from chow-fed dams were compared with males from dams fed a diet high in saturated fat (45 kcal/100 kcal) before mating, pregnancy, and lactation. Offspring were weaned to a standard chow diet or high fat diet. Animals were killed at 120 days after a 24-h fast. Body weight, energy intake, fat deposition, serum leptin, and insulin were significantly higher in offspring from control or high-fat dams if fed a high-fat diet from weaning to adulthood. Only fat-fed offspring from fat-fed dams were hyperglycemic. Leptin receptor, proopiomelanocortin, and neuropeptide Y (NPY) were also significantly increased in offspring exposed to excess saturated fat during gestation and into adulthood, whereas NPY1 receptor was downregulated. Signal transducer and activator of transcription 3 mRNA level was significantly higher in offspring from high-fat-fed dams compared with controls; however, no change was detected in cocaine and amphetamine-regulated transcript or suppressor of cytokine signaling 3. An increase in agouti-related protein expression did not reach significance. A significant reduction in phosphatidylinositol 3-kinase regulatory subunit (p85α) coupled to an upregulation of protein kinase B was observed in offspring from high-fat-fed dams transitioned to chow food, whereas p85α expression was significantly increased in high-fat offspring weaned to the high-fat diet. These data support the hypothesis that early life exposure to excess fat is associated with changes in hypothalamic regulation of body weight and energy homeostasis and that postweaning diet influences development of metabolic dysfunction and obesity.

scholarly journals Impact of perinatal prebiotic consumption on gestating mice and their offspring: a preliminary report

2011 ◽  
Vol 107 (9) ◽  
pp. 1245-1248 ◽  
Author(s):  
Nicolas Desbuards ◽  
Pascal Gourbeyre ◽  
Vianney Haure-Mirande ◽  
Dominique Darmaun ◽  
Martine Champ ◽  
...  
Keyword(s):  
Body Weight ◽  
Muscle Mass ◽  
Body Weight Gain ◽  
Maternal Diet ◽  
The Body ◽  
Pregnancy And Lactation ◽  
Pregnant Mice ◽  
Preliminary Study ◽  
Stomach Weight ◽  
The Impact

To assess the impact of prebiotic supplementation during gestation and fetal and early neonatal life, gestating BALB/cj dam mice were fed either a control or a prebiotic (galacto-oligosaccharides–inulin, 9:1 ratio)-enriched diet throughout pregnancy and lactation, and allowed to nurse their pups until weaning. At the time of weaning, male offspring mice were separated from their mothers, weaned to the same solid diet as their dam and their growth was monitored until killed 48 d after weaning. Prebiotic treatment affected neither the body-weight gain nor the food intake of pregnant mice. In contrast, at the time of weaning, pups that had been nursed by prebiotic-fed dams had a higher body weight (11·0 (se 1·2) g) than pups born from control dams (9·8 (se 0·9) g). At 48 d after weaning, significantly higher values were observed for colon length and muscle mass in the offspring of prebiotic-fed dams (1·2 (se 0·1) cm/cm and 5·7 (se 1·8) mg/g, respectively), compared with control offspring (1·1 (se 0·1) cm/cm and 2·9 (se 0·9) mg/g, respectively), without any difference in spleen and stomach weight, or serum leptin concentration. The present preliminary study suggests that altering the fibre content of the maternal diet during both pregnancy and lactation enhances offspring growth, through an effect on intestinal and muscle mass rather than fat mass accretion.

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