Protein and folic acid content in the maternal diet determine lipid metabolism and response to high-fat feeding in rat progeny in an age-dependent manner

AbstractZbtb7c is a proto-oncoprotein that controls the cell cycle and glucose, glutamate, and lipid metabolism. Zbtb7c expression is increased in the liver and white adipose tissues of aging or high-fat diet-fed mice. Knockout or knockdown of Zbtb7c gene expression inhibits the adipocyte differentiation of 3T3-L1 cells and decreases adipose tissue mass in aging mice. We found that Zbtb7c was a potent transcriptional repressor of SIRT1 and that SIRT1 was derepressed in various tissues of Zbtb7c-KO mice. Mechanistically, Zbtb7c interacted with p53 and bound to the proximal promoter p53RE1 and p53RE2 to repress the SIRT1 gene, in which p53RE2 was particularly critical. Zbtb7c induced p53 to interact with the corepressor mSin3A-HADC1 complex at p53RE. By repressing the SIRT1 gene, Zbtb7c increased the acetylation of Pgc-1α and Pparγ, which resulted in repression or activation of Pgc-1α or Pparγ target genes involved in lipid metabolism. Our study provides a molecular target that can overexpress SIRT1 protein in the liver, pancreas, and adipose tissues, which can be beneficial in the treatment of diabetes, obesity, longevity, etc.

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Peroxisome Proliferator-Activated Receptor α Mediates the Effects of High-Fat Diet on Hepatic Gene Expression

Endocrinology ◽

10.1210/en.2005-1132 ◽

2006 ◽

Vol 147 (3) ◽

pp. 1508-1516 ◽

Cited By ~ 194

Author(s):

David Patsouris ◽

Janardan K. Reddy ◽

Michael Müller ◽

Sander Kersten

Keyword(s):

Fatty Acid ◽

Fatty Acid Oxidation ◽

Microarray Analysis ◽

High Fat Diet ◽

Acid Oxidation ◽

Peroxisome Proliferator ◽

Dependent Manner ◽

Wild Type ◽

High Fat ◽

Fat Feeding

Peroxisome proliferator-activated receptors (PPARs) are transcription factors involved in the regulation of numerous metabolic processes. The PPARα isotype is abundant in liver and activated by fasting. However, it is not very clear what other nutritional conditions activate PPARα. To examine whether PPARα mediates the effects of chronic high-fat feeding, wild-type and PPARα null mice were fed a low-fat diet (LFD) or high-fat diet (HFD) for 26 wk. HFD and PPARα deletion independently increased liver triglycerides. Furthermore, in wild-type mice HFD was associated with a significant increase in hepatic PPARα mRNA and plasma free fatty acids, leading to a PPARα-dependent increase in expression of PPARα marker genes CYP4A10 and CYP4A14. Microarray analysis revealed that HFD increased hepatic expression of characteristic PPARα target genes involved in fatty acid oxidation in a PPARα-dependent manner, although to a lesser extent than fasting or Wy14643. Microarray analysis also indicated functional compensation for PPARα in PPARα null mice. Remarkably, in PPARα null mice on HFD, PPARγ mRNA was 20-fold elevated compared with wild-type mice fed a LFD, reaching expression levels of PPARα in normal mice. Adenoviral overexpression of PPARγ in liver indicated that PPARγ can up-regulate genes involved in lipo/adipogenesis but also characteristic PPARα targets involved in fatty acid oxidation. It is concluded that 1) PPARα and PPARα-signaling are activated in liver by chronic high-fat feeding; and 2) PPARγ may compensate for PPARα in PPARα null mice on HFD.

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Age-dependent effect of high-fructose and high-fat diets on lipid metabolism and lipid accumulation in liver and kidney of rats

Lipids in Health and Disease ◽

10.1186/1476-511x-12-136 ◽

2013 ◽

Vol 12 (1) ◽

pp. 136 ◽

Cited By ~ 46

Author(s):

Uberdan Guilherme Mendes de Castro ◽

Robson Augusto Souza dos Santos ◽

Marcelo Silva ◽

Wanderson de Lima ◽

Maria Campagnole-Santos ◽

...

Keyword(s):

Lipid Metabolism ◽

Lipid Accumulation ◽

High Fat ◽

Dependent Effect ◽

High Fructose ◽

High Fat Diets ◽

Age Dependent ◽

Liver And Kidney ◽

Fat Diets

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Similar changes in muscle lipid metabolism are induced by chronic high-fructose feeding and high-fat feeding in C57BL/J6 mice

Clinical and Experimental Pharmacology and Physiology ◽

10.1111/1440-1681.12017 ◽

2012 ◽

Vol 39 (12) ◽

pp. 1011-1018 ◽

Cited By ~ 9

Author(s):

Guang-Yao Song ◽

Lu-Ping Ren ◽

Shu-Chun Chen ◽

Chao Wang ◽

Na Liu ◽

...

Keyword(s):

Lipid Metabolism ◽

High Fat ◽

Muscle Lipid ◽

High Fructose ◽

Fat Feeding

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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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Maternal high-fat diet programs white and brown adipose tissue lipidome and transcriptome in offspring in a sex- and tissue-dependent manner in mice

International Journal of Obesity ◽

10.1038/s41366-021-01060-5 ◽

2022 ◽

Author(s):

Christina Savva ◽

Luisa A. Helguero ◽

Marcela González-Granillo ◽

Tânia Melo ◽

Daniela Couto ◽

...

Keyword(s):

High Fat Diet ◽

Metabolic Profile ◽

Maternal Diet ◽

Overweight And Obesity ◽

Male Offspring ◽

Metabolic Adaptation ◽

Dependent Manner ◽

High Fat ◽

The Metabolic Syndrome ◽

Metabolic Complication

Abstract Objective The prevalence of overweight and obesity among children has drastically increased during the last decades and maternal obesity has been demonstrated as one of the ultimate factors. Nutrition-stimulated transgenerational regulation of key metabolic genes is fundamental to the developmental origins of the metabolic syndrome. Fetal nutrition may differently influence female and male offspring. Methods Mice dam were fed either a control diet or a high-fat diet (HFD) for 6-week prior mating and continued their respective diet during gestation and lactation. At weaning, female and male offspring were fed the HFD until sacrifice. White (WAT) and brown (BAT) adipose tissues were investigated in vivo by nuclear magnetic resonance at two different timepoints in life (midterm and endterm) and tissues were collected at endterm for lipidomic analysis and RNA sequencing. We explored the sex-dependent metabolic adaptation and gene programming changes by maternal HFD in visceral AT (VAT), subcutaneous AT (SAT) and BAT of offspring. Results We show that the triglyceride profile varies between adipose depots, sexes and maternal diet. In female offspring, maternal HFD remodels the triglycerides profile in SAT and BAT, and increases thermogenesis and cell differentiation in BAT, which may prevent metabolic complication later in life. Male offspring exhibit whitening of BAT and hyperplasia in VAT when born from high-fat mothers, with impaired metabolic profile. Maternal HFD differentially programs gene expression in WAT and BAT of female and male offspring. Conclusion Maternal HFD modulates metabolic profile in offspring in a sex-dependent manner. A sex- and maternal diet-dependent gene programming exists in VAT, SAT, and BAT which may be key player in the sexual dimorphism in the metabolic adaptation later in life.

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Effects of high-fat feeding on ectopic fat storage and postprandial lipid metabolism in mouse offspring

Obesity ◽

10.1002/oby.21235 ◽

2015 ◽

Vol 23 (11) ◽

pp. 2242-2250 ◽

Cited By ~ 1

Author(s):

Petronella A. van Ewijk ◽

Sabina Paglialunga ◽

M. Eline Kooi ◽

Patricia M. Nunes ◽

Anne Gemmink ◽

...

Keyword(s):

Lipid Metabolism ◽

Ectopic Fat ◽

High Fat ◽

Fat Storage ◽

Postprandial Lipid Metabolism ◽

Postprandial Lipid ◽

Fat Feeding

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Fructose supplementation worsens the deleterious effects of short-term high-fat feeding on hepatic steatosis and lipid metabolism in adult rats

Experimental Physiology ◽

10.1113/expphysiol.2014.079632 ◽

2014 ◽

Vol 99 (9) ◽

pp. 1203-1213 ◽

Cited By ~ 37

Author(s):

Raffaella Crescenzo ◽

Francesca Bianco ◽

Paola Coppola ◽

Arianna Mazzoli ◽

Margherita Tussellino ◽

...

Keyword(s):

Lipid Metabolism ◽

Hepatic Steatosis ◽

High Fat ◽

Short Term ◽

Adult Rats ◽

Fat Feeding

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Maternal High-Fat Feeding Affects the Liver and Thymus Metabolic Axis in the Offspring and Some Effects Are Attenuated by Maternal Diet Normalization in a Minipig Model

Metabolites ◽

10.3390/metabo11120800 ◽

2021 ◽

Vol 11 (12) ◽

pp. 800

Author(s):

Federica La Rosa ◽

Letizia Guiducci ◽

Maria Angela Guzzardi ◽

Andrea Cacciato Insilla ◽

Silvia Burchielli ◽

...

Keyword(s):

Weight Gain ◽

Maternal Diet ◽

Liver Steatosis ◽

Normal Diet ◽

Liver Fat ◽

High Fat ◽

Immune Development ◽

Severe Insulin Resistance ◽

Positron Emission ◽

Fat Feeding

Maternal high-fat diet (HFD) affects metabolic and immune development. We aimed to characterize the effects of maternal HFD, and the subsequent diet-normalization of the mothers during a second pregnancy, on the liver and thymus metabolism in their offspring, in minipigs. Offspring born to high-fat (HFD) and normal diet (ND) fed mothers were studied at week 1 and months 1, 6, 12 of life. Liver and thymus glucose uptake (GU) was measured with positron emission tomography during hyperinsulinemic-isoglycemia. Histological analyses were performed to quantify liver steatosis, inflammation, and hepatic hematopoietic niches (HHN), and thymocyte size and density in a subset. The protocol was repeated after maternal-diet-normalization in the HFD group. At one week, HFDoff were characterized by hyperglycemia, hyperinsulinemia, severe insulin resistance (IR), and high liver and thymus GU, associating with thymocyte size and density, with elevated weight-gain, liver IR, and steatosis in the first 6 months of life. Maternal diet normalization reversed thymus and liver hypermetabolism, and increased HHN at one week. It also normalized systemic insulin-sensitivity and liver fat content at all ages. Instead, weight-gain excess, hyperglycemia, and hepatic IR were still observed at 1 month, i.e., end-lactation. We conclude that intra-uterine HFD exposure leads to time-changing metabolic and immune-correlated abnormalities. Maternal diet-normalization reversed most of the effects in the offspring.

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