Excess Folic Acid Increases Lipid Storage, Weight Gain, and Adipose Tissue Inflammation in High Fat Diet-Fed Rats

Kelly, Karen B.; Kennelly, John P.; Ordoñez, Marta; Nelson, Randal C.; Stabler, Sally P.; Gómez-Muñoz, Antonio; Field, Catherine J.; Jacobs, René L.

doi:10.3390/nu8100594

Cited by 42 publications

(32 citation statements)

References 42 publications

(69 reference statements)

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“…Inflammation is increased in rats fed with high-fat-adequate FA (HF-AFA), and this increase is associated with impaired glucose tolerance compared with HF-EFA-fed rats. FA induces the PPARγ expression and triglyceride accumulation in 3T3-L1 cells [26]. FA may influence the pathogenesis of CHDs through other more complex pathways, including epigenetic mechanisms responsible for transgenerational effects [27].…”

Section: Discussionmentioning

confidence: 99%

Long Non-Coding RNA Expression Profiling in Obesity Mice with Folic Acid Supplement

Ma¹,

Li²,

Tang³

et al. 2017

Cell Physiol Biochem

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Background/Aims: Obesity is a major contributor to the growing prevalence of metabolic and cardiovascular diseases. This study was designed to investigate the effect of folic acid (FA) on obese mice by detecting the genome-wide expression profile of lncRNAs and mRNAs in the heart. Methods: Heart samples were collected from mice fed with standard diet (SD), highfat diet (HFD) and high-fat diet with FA intake (HFDF). LncRNAs and mRNAs between HFD and HFDF group were analyzed by lncRNA microarray. Nine lncRNAs and mRNAs were validated using quantitative reverse transcription polymerase chain reaction (qRT-PCR). Bioinformatics prediction was used to investigate the potential function of these differentially expressed lncRNAs. Co-expresson analysis was used to determine the transcriptional regulatory relationship of differentially expressed lncRNAs and mRNAs between two groups. Results: The expression of 58,952 lncRNAs and 20,145 mRNAs in HFD and HFDF groups was profiled by using microarrays. Gene Ontology and pathway analyses indicated that the biological functions of differentially expressed mRNAs were related to inflammation, energy metabolism, and cell differentiation. Co-expression networks composed of lncRNAs and mRNAs were also constructed to investigate the potential regulatory roles of differentially expressed lncRNAs on mRNAs. LncRNAs, namely, NONMMUT033847, NONMMUT070811, and NONMMUT015327, were validated through qRT-PCR, and these lncRNAs may be important factors regulating inflammation, energy metabolism, and cell differentiation. The expression levels of Dnajb1, Egr2, Hba-a1, Il1β, Cxcl2, and Tnfsf9 were significantly different between HFD and HFDF. Conclusions: Results suggested that FA may improve the cardiovascular function of obesity and contribute to those lncRNAs associated with inflammation and cell differentiation. In a nutshell, the present study identified a panel of lncRNAs and mRNAs that may be potential biomarkers or drug targets relevant to the high-fat diet related obesity.

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Section: Discussionmentioning

confidence: 99%

Long Non-Coding RNA Expression Profiling in Obesity Mice with Folic Acid Supplement

Ma¹,

Li²,

Tang³

et al. 2017

Cell Physiol Biochem

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show abstract

“…Intake of vitamins A and D during pregnancy can also affect gene expression in offspring (15,16). In animal studies, excess folic acid may exacerbate weight gain, fat accumulation, and inflammation caused by consumption of a high fat diet (17). Mothers exposed to high folic acid (HFA), have increased weight gain and reveal hyperphagia and hyperdypsia after the end of HFA exposure.…”

Section: Epigenetic Changesmentioning

confidence: 99%

Epigenetic Basis of Twin Discordance in Diseases: Future Benefits

Demir

2018

Gynecol Obstet Reprod Med

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Monozygotic twins share the same genotype since they are derived from the same zygote. However, monozygotic twin siblings frequently present many phenotypic differences, such as their susceptibilities to diseases. These isogenic individuals are not entirely identical. They exhibit phenotypic incompatibility for many features, from birth weight to complex diseases. Recently, several studies have been published showing that phenotypic differences, especially in monozygotic twins, are being induced from prenatal period to life-long epigenetic differences. Epigenetic studies on twins have a great potential to contribute to our understanding of complex diseases, such as cancer, autoimmune disorders, psychiatric disorders and neurological diseases. Since monozygotic twins are genetic clones (genetically identical), they are considered as perfect models for studying the role of environmental factors as determinants of complex diseases and phenotypes. In this review, a number of intrauterine effects and genetic mechanisms that may affect phenotypic, genotypic, and epigenetic differences between monozygotic twins were described and effects of epigenetic mechanisms on complex diseases were mentioned. Further work on epigenetic changes in diseases using incompatible monozygotic twin models, would lead to new developments in medical therapies.

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“…It is not well defined what would be the most appropriate diet to build up the triad in experimental models: obesity complications, and comorbidities. For this purpose, several authors use diets rich in fatty acids [14][15][16][17][18]. In diets using predominantly unsaturated fat, the rodents develop obesity and different types of complications associated, whereas comorbidities are not common manifestations [19,20].…”

Section: Introductionmentioning

confidence: 99%

The influence of obesity by a diet high in saturated fats and carbohydrates balance in the manifestation of systemic complications and comorbidities

Adorni

Corrêa

Vileigas

et al. 2017

Nutrire

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Background: The aim of this study is to test the hypothesis that obesity induced by a diet rich in saturated fats and balanced in carbohydrates is associated with the development of systemic complications and comorbidities. Methods: Thirty-seven 60-day-old male Wistar rats were randomized into two groups: control (C, n = 18, standard diet) and obese (OB, n = 19, high-saturated fat diet), for 33 weeks. Nutritional profile: food and caloric intake, feed efficiency, body weight, and adiposity index. Complications: in plasma were analyzed dyslipidemia, insulin resistance (HOMA-IR), glucose intolerance, hyperleptinemia, hyperinsulinemia, plasmatic C-reactive protein (CRP), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-α); in the myocardial and epididymal adipose tissue were assessed IL-6 and TNF-α. Comorbidities: diabetes mellitus and systemic blood pressure (SBP). Student's t test, ANOVA, and Bonferroni P < 0.05. Results: The final body weight, feed efficiency, and adiposity index were higher in OB group than in control; although food intake was lower in OB group, caloric intake was similar in both groups. Specific parameters, such as LDL, cholesterol, triglycerides, HOMA-IR, CRP, TNF-α in epididymal adipose tissue, and IL-6 in the myocardium, were higher in obese rats than in controls. SBP, baseline glucose, and glucose after 2 h of overload were significantly increased in OB group; however, the severity was not enough to classify the animals as diabetic and hypertensive. Conclusion: Obesity induced by a diet high in saturated fatty acids with balanced carbohydrates for 33 weeks in Wistar rats was effective in triggering complications but unable to develop comorbidities.

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Excess Folic Acid Increases Lipid Storage, Weight Gain, and Adipose Tissue Inflammation in High Fat Diet-Fed Rats

Cited by 42 publications

References 42 publications

Long Non-Coding RNA Expression Profiling in Obesity Mice with Folic Acid Supplement

Long Non-Coding RNA Expression Profiling in Obesity Mice with Folic Acid Supplement

Epigenetic Basis of Twin Discordance in Diseases: Future Benefits

The influence of obesity by a diet high in saturated fats and carbohydrates balance in the manifestation of systemic complications and comorbidities

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