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

Page, Kathleen Creed; Malik, Raleigh E.; Ripple, Joshua A.; Anday, Endla K.

doi:10.1152/ajpregu.90585.2008

Cited by 109 publications

(104 citation statements)

References 44 publications

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“…The origin of other metabolic diseases in the adult can be also related with maternal overnutrition, such as hypertension and hyperlipidemia (Elahi et al, 2009) or insulin resistance and diabetes (Samuelsson et al, 2008), and maternal HFD is associated with changes in hypothalamic regulation of body weight and energy homeostasis by altering the expression of leptin receptor, proopiomelanocortin, and neuropeptide Y in the adult offspring (Page et al, 2009). Nevertheless, not all the studies arise to the same conclusion.…”

Section: Hypercaloric and High-fat Dietsmentioning

confidence: 99%

Dietary factors, epigenetic modifications and obesity outcomes: Progresses and perspectives

Milagro

Mansego

Miguel

et al. 2013

Molecular Aspects of Medicine

257

161

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Nutritional factors play a life-long role in human health. Indeed, there is growing evidence that one of the mechanisms by which nutrients and bioactive compounds affect metabolic traits is epigenetics. Complex interactions among food components and histone modifications, DNA methylation, non-coding RNA expression and chromatin remodeling factors lead to a dynamic regulation of gene expression that controls the cellular phenotype. Although perinatal period is the time of highest phenotypic plasticity, contributing largely to developmental programming, also during adulthood there is evidence about a nutritional influence on epigenetic regulation. Similarly to type 2 diabetes, hypertension, atherosclerosis and other metabolic disorders, obesity predisposition and weight loss outcomes have been repeatedly associated to changes in epigenetic patterns. Different non-nutritional risk factors that usually accompany obesity seem also to be involved in these epigenetic modifications, especially hyperglycemia, inflammation, hypoxia and oxidative stress. There are currently three major objectives in epigenetic research in relation to obesity: to search for epigenetic biomarkers to predict future health problems or detect the individuals at most risk, to understand the obesity-related environmental factors that could modulate gene expression by affecting epigenetic mechanisms, and to study novel therapeutic strategies based on nutritional or pharmacological agents that can modify epigenetic marks. At this level, the major tasks are: development of robust epigenetic biomarkers of weight regulation, description of those epigenetic marks more susceptible to be modified by dietary exposures, identification of the active ingredients (and the doses) that alter the epigenome, assessment of the real importance of other obesity-related factors on epigenetic regulation, determination of the period of life in which best results are obtained, and understanding of the importance of the inheritance of these epigenetic marks.

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Section: Hypercaloric and High-fat Dietsmentioning

confidence: 99%

Dietary factors, epigenetic modifications and obesity outcomes: Progresses and perspectives

Milagro

Mansego

Miguel

et al. 2013

Molecular Aspects of Medicine

257

161

View full text Add to dashboard Cite

show abstract

“…In addition, leptin programming in utero might influence the food intake regulatory system throughout life. The offspring of dams fed a high-fat diet during gestation were heavier and concomitantly had higher hypothalamic mRNA expression of leptin receptors, proopiomelanocortin, and neuropeptide Y [38]. Vogt et al [39] showed that abnormal insulin signaling in murine progeny caused by high-fat diet feeding of dams interferes with the formation of the hypothalamic neural circuits that contribute to metabolic status.…”

Section: Discussionmentioning

confidence: 99%

A Calcium-Deficient Diet in Rat Dams during Gestation Decreases HOMA-β% in 3 Generations of Offspring

Takaya

Yamanouchi²,

Tanabe³

et al. 2016

Lifestyle Genomics

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Background: Prenatal malnutrition can affect the phenotype of offspring by altering epigenetic regulation. Calcium (Ca) plays an important role in the pathogenesis of insulin resistance syndrome. Aims: We hypothesized that a Ca-deficient diet during pregnancy would alter insulin resistance and secretion in more than 1 generation of offspring. Methods: Female Wistar rats consumed either a Ca-deficient or a control diet ad libitum from 3 weeks before conception to 21 days after parturition and were mated with control males. Randomly selected F1 and F2 females were mated with males of each generation on postnatal day 70. The F1 and F2 dams were fed a control diet ad libitum during pregnancy and lactation. All offspring were fed a control diet starting at the time of weaning and were sacrificed on day 180. Results: HOMA-β% decreased in F1 through F3, and levels in F2 and F3 males and females were significantly lower than in controls. The mean levels of insulin and HOMA-IR were higher in F1 males but lower in F3 males than in control males. The HOMA-IR did not differ between any of the female offspring and controls. Conclusions: Maternal Ca restriction during pregnancy and/or lactation influences insulin secretion in 3 generations of offspring.

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“…It has been shown that a reduction in the catalytic subunit p85a of PI3K enhances insulinstimulated Akt activity (34). It was reported that PI3K subunit p85a was upregulated in the hypothalamus of mice that were exposed to an HFD throughout IU/L and the first 120 days of life (35). HFD-induced obesity was shown to require activation of PI3K-dependent hypothalamic pathways (36).…”

Section: Discussionmentioning

confidence: 99%

High-Fat Diet During Mouse Pregnancy and Lactation Targets GIP-Regulated Metabolic Pathways in Adult Male Offspring

et al. 2015

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Maternal obesity is a worldwide problem associated with increased risk of metabolic diseases in the offspring. Genetic deletion of the gastric inhibitory polypeptide (GIP) receptor (GIPR) prevents high-fat diet (HFD)-induced obesity in mice due to specific changes in energy and fat cell metabolism. We investigated whether GIP-associated pathways may be targeted by fetal programming and mimicked the situation by exposing pregnant mice to control or HFD during pregnancy (intrauterine [IU]) and lactation (L). Male wild-type (WT) and Gipr 2/2 offspring received control chow until 25 weeks of age followed by 20 weeks of HFD. Gipr 2/2 offspring of mice exposed to HFD during IU/L became insulin resistant and obese and exhibited increased adipose tissue inflammation and decreased peripheral tissue substrate utilization after being reintroduced to HFD, similar to WT mice on regular chow during IU/L. They showed decreased hypothalamic insulin sensitivity compared with Gipr 2/2 mice on control diet during IU/L.DNA methylation analysis revealed increased methylation of CpG dinucleotides and differential transcription factor binding of promoter regions of genes involved in lipid oxidation in the muscle of Gipr 2/2 offspring on HFD during IU/L, which were inversely correlated with gene expression levels. Our data identify GIP-regulated metabolic pathways that are targeted by fetal programming.Gastric inhibitory polypeptide (GIP) is released from the duodenum after nutrient intake and regulates postprandial insulin secretion (1). GIP is known for its anabolic effects in adipocytes (2) and has been shown to stimulate the activity of lipoprotein lipase in adipose tissue in vitro (3) (4). Genetic ablation of the GIP receptor (GIPR) protects from high-fat diet (HFD)-induced obesity and insulin resistance in mice (5). GIPR knockout (Gipr) mice use fat as energy substrate rather than storing it in adipocytes. Moreover, central appetite-regulating pathways are downregulated in ovariectomized female Gipr 2/2 mice (6), and energy expenditure is increased in Gipr 2/2 mice exposed to a high-glycemic index diet (7) or an HFD (8).Since Gipr 2/2 mice are protected from obesity when exposed to a postweaning HFD, we hypothesized that this phenotype may be lost when these mice were exposed to the same HFD during pregnancy (intrauterine [IU]) and lactation (L). The IU milieu has a persisting influence on the development of adult diseases (9,10). Maternal caloric malnutrition as well as overnutrition during IU and L can induce metabolic disturbances later in life in offspring (11,12). Animal studies have shown that mice exposed to a maternal HFD during IU/L and weaned onto a standard chow developed adiposity, insulin resistance, and hepatosteatosis later in life (13,14). Not only the diet during IU/L but also the postweaning diet is important for the manifestation of metabolic diseases. Studies investigating the interaction of an HFD during IU/L and postweaning usually apply the HFD continuously from premating throughout the end of the study in ...

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

Cited by 109 publications

References 44 publications

Dietary factors, epigenetic modifications and obesity outcomes: Progresses and perspectives

Dietary factors, epigenetic modifications and obesity outcomes: Progresses and perspectives

A Calcium-Deficient Diet in Rat Dams during Gestation Decreases HOMA-β% in 3 Generations of Offspring

High-Fat Diet During Mouse Pregnancy and Lactation Targets GIP-Regulated Metabolic Pathways in Adult Male Offspring

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