Maternal cafeteria diet influences kisspeptin (Kiss1), kisspeptin receptor(Gpr54), and sirtuin (Sirt1) genes, hormonal and metabolic profiles, and reproductive functions in rat offspring in a sex-specific manner†.

Kisspeptin (KP, encoded by Kiss1, binding to the Gpr54 receptor) is a neuropeptide conveying information on the metabolic status to the hypothalamic-pituitary-gonadal axis. KP acts together with dynorphin A (encoded by Pdyn) and neurokinin B (encoded by Tac2) to regulate reproduction. KP is crucial for the onset of puberty and is under the control of sirtuin (encoded by Sirt1). We hypothesize that the maternal cafeteria (CAF) diet has adverse effects on the offspring's hormonal, metabolic, and reproductive functions due to sex-specific alterations in the expression of Kiss1, Gpr54, Pdyn, Tac2, and Sirt1 in the hypothalamus, and Kiss1, Gpr54, and Sirt1 in the liver. Rats were fed a CAF diet before pregnancy, during pregnancy, and during lactation. The vaginal opening was monitored. Offspring were sacrificed in three age points: PND 30, PND 35, and PND 60 (females) and PND 40, PND 45, and PND 60 (males). Their metabolic and hormonal status was assessed. mRNA for Kiss1, Gpr54, Pdyn, Tac2, and Sirt1 were measured by real-time PCR in the hypothalamus and/or livers. We found that CAF offspring had lower weight and altered body composition; increased cholesterol and triglyceride levels, sex-specific changes in glucose and insulin levels; sex-dependent changes in Sirt1/Kiss1 mRNA ratio in the hypothalamus; sex-specific alterations in Kiss1 and Sirt1 mRNA in the liver with more diversity in males; and a delayed puberty onset in females. We concluded that the mother's CAF diet leads to sex-specific alterations in metabolic and reproductive outcomes via Kiss1/Gpr54 and Sirt1 systems in offspring.

The Impacts of Combined Blood Flow Restriction Training and Betaine Supplementation on One-Leg Press Muscular Endurance, Exercise-Associated Lactate Concentrations, Serum Metabolic Biomarkers, and Hypoxia-Inducible Factor-1α Gene Expression.

The purpose of this investigation was to compare the impacts of a potential blood flow restriction (BFR)-betaine synergy on one-leg press performance, lactate concentrations, and exercise-associated biomarkers. Eighteen recreationally trained males (25 ± 5 y) were randomized to supplement 6 g/day of either betaine anhydrous (BET) or cellulose placebo (PLA) for 14 days. Subsequently, subjects performed four standardized sets of one-leg press and two additional sets to muscular failure on both legs (BFR [LL-BFR; 20% 1RM at 80% arterial occlusion pressure] and high-load [HL; 70% 1RM]). Toe-tip lactate concentrations were sampled before (PRE), as well as immediately (POST0), 30 min (POST30M), and 3 h (POST3H) post-exercise. Serum homocysteine (HCY), growth hormone (GH) and insulin-like growth factor-1 concentrations were additionally assessed at PRE and POST30M. Analysis failed to detect any significant between-supplement differences for total repetitions completed. Baseline lactate changes (∆) were significantly elevated from POST0 to POST30 and from POST30 to POST3H (p < 0.05), whereby HL additionally demonstrated significantly higher ∆Lactate versus LL-BFR (p < 0.001) at POST3H. Although serum ∆GH was not significantly impacted by supplement or condition, serum ∆IGF-1 was significantly (p = 0.042) higher in BET versus PLA and serum ∆HCY was greater in HL relative to LL-BFR (p = 0.044). Although these data fail to support a BFR-betaine synergy, they otherwise support betaine's anabolic potential.

The effects of folate and iron deficiency followed by supplementation on blood morphology and inflammation biomarkers in rats.

BACKGROUND: Little is known about the relation between iron and folic acid (FA) supplementation and inflammation. The aim of this study was to evaluate the effects of iron and folate deficiency and supplementation on blood morphology parameters, and to assess the role of iron and folate transporters in inflammation. METHODS: A four-week period of FA and iron deficiency in Wistar rats was followed by randomization into a group fed with a diet deficient in FA and supplemented with Fe (DFE), a group fed a diet deficient in Fe and supplemented with FA (DFOL), a group fed a diet supplemented with Fe and FA (FEFOL), a group fed a diet deficient in Fe and FA (D), and a group fed a control diet (C). The blood Crp concentration and blood count were determined. The expression of SLC11A2, SLC46A1, SLC19A1, and TFR2 proteins was assessed using the western blot method. RESULTS: After ten days on the experimental diets, the rats in the DFOL group had a 21% higher concentration of white blood cells (WBC) than the FEFOL group did (p < 0.05). We did not observe any differences between the groups in terms of C-reactive protein (Crp) concentration. We also did not find any other differences between the groups in other morphological parameters. Analysis of the correlation between blood count parameters and the expression of iron and folate transporters gave conflicting results. CONCLUSIONS: To conclude, iron and folate supplementation may affect WBC concentration in the blood.

Hedonic Hunger Is Associated with Intake of Certain High-Fat Food Types and BMI in 20- to 40-Year-Old Adults.

BACKGROUND: Hedonic hunger occurs in response to a desire to consume food for pleasure. The µ-opioid system regulates the hedonic impact of food and the opioid receptor mu 1 gene (OPRM1) polymorphism has been associated with fat intake. OBJECTIVES: The aim of this study was to determine whether the intake of high-fat food is associated with hedonic hunger and the OPRM1 polymorphism and whether these variables are related to BMI. METHODS: Participants were 20- to 40-y-old women and men enrolled in Poznan, Poland in 2016-2018. The frequency of consumption of high-fat food was measured using a validated application for mobile devices. Hedonic hunger was assessed with the use of the Power of Food Scale (PFS). PFS1, PFS2, and PFS3 scores were generated for food available, food present, and food tasted, respectively. Genotyping of rs1799971 in the OPRM1 gene was performed using TaqMan probes. The associations were analyzed using linear regression or logistic regression, as appropriate. RESULTS: Hedonic hunger scores were not associated with total high-fat food intake. Total PFS was associated with snack intake (ß: 0.16, P = 0.0066). PFS1 was positively associated with healthy high-fat food intake (ß: 0.27, P = 0.0001) and PFS2 with sweet high-fat food and fast-food intake (ß: 0.27, P = 0.0030). OPRM1 genotype and hedonic hunger interacted on fast-food intake (ß: -0.17; P < 0.0154). Total PFS and PFS2 increased the chance of having a BMI ≥ 25 kg/m2 (OR: 1.43; 95% CI: 1.03, 2.01; P = 0.0335 and OR: 1.89; 95% CI: 1.37, 2.61; P = 0.0001, respectively), whereas PFS3 decreased it (OR: 0.61; 95% CI: 0.41, 0.87; P = 0.0082). CONCLUSIONS: Hedonic hunger is associated with the intake of selected types of high-fat food, but not with its total intake, in people aged 20-40 y. Associations between hedonic hunger and fast-food intake can be modified by OPRM1 genotype. Hedonic hunger is associated with BMI.

Effect of Iron and Folic Acid Supplementation on the Level of Essential and Toxic Elements in Young Women.

Although simultaneous supplementation of iron and folic acid is justified, the potential interactions between these micronutrients and other elements are poorly known. In this study, we aimed to investigate the effect of iron and folic acid supplementation on the levels of selected essential and toxic elements in the serum of micronutrient-deficient young women. A total of 40 women participated in this study and were divided into two groups: study group (n = 23) (with iron and folate deficiency) and control group (n = 17). The study group received iron and folic acid supplements for 3 months. Blood samples were collected at baseline and after the completion of the study period. Women completed a 3-day food intake record. We calculated the body mass index (BMI) of all the participants. Cellular morphology was analyzed in whole blood, and biochemical parameters were determined in serum. Elements were measured in serum by inductively coupled plasma mass spectrometry (ICP-MS). According to our results, in the case of the study group, the supplementation of iron and folic acid restored their levels; however, it caused a significant decrease in the level of zinc, calcium, and magnesium. In the case of the control group, at the end of the study period, there was a marked decrease in the level of iron. Interestingly, there was an increase in the level of arsenic and vanadium in both groups. In conclusion, simultaneous supplementation of iron and folic acid impairs the level of zinc, calcium, and magnesium in women of childbearing age.

Greater self-reported preference for fat taste and lower fat restraint are associated with more frequent intake of high-fat food.

The determinants of the intake of high-fat products are not well recognized, but fat preference may be one of them. The aim of this study was thus to determine whether intake of different types of high-fat food is associated with fat preference in people with normal and increased body weight. Participants aged 20-40 years [n = 421] were enrolled in Poznan, Poland in 2016-2018. Fat preference was measured using the Fat Preference Questionnaire. Self-reported preference for fat taste (TASTE) and fat restraint (DIFF) scores were calculated. The frequency of consuming high-fat food was measured with an application for mobile devices using ecological momentary assessment. TASTE was positively associated with calorie intake and total frequency of eating high-fat food in both the normal weight and the overweight/obese groups. Overweight and obese people had lower DIFF (p < 0.001) than normal weight people. DIFF was negatively associated with total calorie intake and total intake of high-fat food, but only in normal weight people (ß = -0.16, p < 0.01 and ß = -0.26, p < 0.001, respectively). DIFF was negatively associated with the frequency of eating sweet (ß = -0.33, p < 0.000) and meat high-fat food (ß = -0.25, p < 0.001) in the normal weight group. The frequency of consumption of high-fat food and calorie intake are positively associated with self-reported preference for fat taste. In normal weight subjects fat restraint is negatively associated with calorie intake and total frequency of high-fat food intake, as well as with intake of different types of fatty food. Fat preference measures are thus associated with high-fat food intake, but these associations differ by body weight status.

Role of Slc19a1 and Tfr2 in liver transport of iron and folate: A rat model of folate/iron deficiency followed by supplementation.

The aim of this study was to determine how folate and iron deficiency, and the subsequent supplementation of rats' diet with these nutrients, affects Slc19a1and Tfr2 gene expression and the metabolism of folate and iron. After 28 days of iron-folate deficiency 150 female rats were randomized into five experimental groups receiving a diet deficient in folic acid (FA), an iron-supplemented diet (DFE), an iron-deficient diet supplemented with FA (DFOL), a diet supplemented with iron and FA (FEFOL), and a diet deficient in iron and FA (D); there was also a control group (C). Samples were collected on days 2, 10, and 21 of the experiment. After two days of supplementation, Tfr2 mRNA level were 78 % lower in the DFE group than in the C group (p < 0.05); after 10 days, TfR2 levels in the FEFOL group were 82 % lower than in the C and the DFE group (p < 0.01). However, we did not find any differences at the protein level at any time-point. Hepcidin concentrations were higher in the DFE and the DFEFOL groups than in the D group after 21 days of supplementation (p < 0.01). Transcript and protein abundance of Slc19a1 gene did not differ between the groups at any time-point. Iron metabolism was affected by iron and folate deficiency and subsequent supplementation with these micronutrients, but TFR2 protein was not involved in the regulatory mechanism. Hepcidin expression can be are upregulated after 21 days of supplementation with 150 mg of iron/ kg of diet.

Polymorphism of CD36 Determines Fat Discrimination but Not Intake of High-Fat Food in 20- to 40-Year-Old Adults.

BACKGROUND: The determinants of the intake of high-fat products are not well understood. OBJECTIVE: The aim of this study was to examine the relations between fat perception, intake of high-fat food, and body-weight status, taking into account the polymorphism of the genes that encode the proteins involved in oral fat perception. METHODS: A total of 421 participants aged 20-40 y were enrolled in Poznan, Poland, from 2016 to 2018. An ascending forced-choice triangle procedure was applied to determine fat discrimination ability. Salad dressings with varying concentrations of canola oil were used as stimuli. Genotyping of rs1761667 (CD36) rs1573611 [free fatty acid receptor 1 (FFAR1)], rs17108973 [free fatty acid receptor 4 (FFAR4)], and rs2274333 (CA6) was performed using TaqMan probes. The frequency of consumption of high-fat foods was measured using an application for mobile devices that uses the ecological momentary assessment approach. The associations were analyzed using linear regression or logistic regression, as appropriate. RESULTS: Individuals with the GG CD36 genotype were twice as likely to be fat discriminators, compared with the A allele carriers (P < 0.05). The mean total consumption of high-fat food was 45.8 (44.6, 47.0) times/wk and was not associated with fat discrimination or body-weight status. Obese and overweight subjects ate healthy high-fat food less frequently than did participants with normal body weight, at 4.53 (3.83, 5.23) versus 6.68 (5.82, 7.55) times/wk, respectively (P < 0.001). Men ate sweet high-fat food and snacks 15% less frequently than did women (P < 0.001 and P < 0.05) but consumed high-fat meat and fast food almost 40% more often than did women (P < 0.001 for both associations). CONCLUSIONS: In individuals aged 20-40 y, fat discrimination ability is associated with polymorphism of CD36 but not with the choice of high-fat food. The frequency of consumption of different types of high-fat foods varies by sex and body-weight status.

Associations between folate and choline intake, homocysteine metabolism, and genetic polymorphism of MTHFR, BHMT and PEMT in healthy pregnant Polish women.

AIM: Physiological homocysteine (Hcy) concentrations depend on several factors, both dietary (including folate and choline intake) and biological (such as polymorphism of the genes involved in Hcy metabolism). This study aimed to thus test the associations between genes functionally linked with Hcy metabolism (MTHFR, BHMT and PEMT), folate and choline intakes, and total Hcy (tHcy) concentrations of healthy pregnant women. METHODS: One hundred and three healthy Polish women aged 18-44 years, in the third trimester of pregnancy, were enrolled. RESULTS: Mean blood tHcy and glutathione (GSH) concentrations were 8.08 ± 3.25 µM and 4.84 ± 1.21 µM, respectively. Concentrations of tHcy were found to be lower in the women who were taking folic acid supplements than in those who did not take these supplements (7.42 ± 1.78 µM vs 9.28 ± 4.42 µM, P < 0.05). There were no associations found between the examined parameters and BHMT (rs7356530), MTHFR (rs1801133) and PEMT (rs12325817) alone. However, blood tHcy concentrations differed in the PEMT genotype subgroups when choline and folate intakes were considered: respectively, 25% and 20% lower levels were observed in the C allele carriers who met their needs of choline or folate than in those who did not take enough these nutrients (P < 0.05 for both associations). CONCLUSIONS: This study suggests that choline and folate intakes might interact with MTHFR, BHMT and PEMT polymorphisms to determine tHcy and GSH blood concentrations in healthy pregnant women.

One-Carbon Metabolism and Nonalcoholic Fatty Liver Disease: The Crosstalk between Nutrients, Microbiota, and Genetics.

The prevalence of nonalcoholic fatty liver disease (NAFLD) is increasing worldwide. Its etiology includes nutritional, genetic, and lifestyle factors. Several mechanisms may link one-carbon metabolism - the associated metabolic pathways of folate, methionine, and choline - to the onset of NAFLD. In this review, we attempted to assess how choline, folate, methionine, and betaine affect NAFLD development, mainly through their role in the secretion of very low-density lipoproteins (VLDL) from the liver. We also reviewed recent articles that have described the relation between microbiota metabolism and NAFLD progression. Moreover, we describe the effect of single-nucleotide polymorphisms (SNP) in genes related to one-carbon metabolism and disease prevalence. We additionally seek SNP identified by genome-wide associations that may increase the risk of this disease. Even though the evidence available is not entirely consistent, it seems that the concentrations of choline, methionine, folate, and betaine may affect the progression of NAFLD. Since there is no effective therapy for NAFLD, further investigations into the link between nutrition, gut microbiota, genetic factors, and NAFLD are still necessary, with a particular emphasis on methyl donors.

Folate and choline absorption and uptake: Their role in fetal development.

SCOPE: In this review, we attempt to assess how choline and folate transporters affect fetal development. We focus on how the expression of these transporters in response to choline and folate intake affects transport effectiveness. We additionally describe allelic variants of the genes encoding these transporters and their phenotypic effects. METHODS AND RESULTS: We made an extensive review of recent articles describing role of choline and folate - with particularly emphasize on their transporters - in fetal development. Folate and choline are necessary for the proper functioning of the cell and body. During pregnancy, the requirements of these nutrients increase because of elevated maternal demand and the rapid division of fetal cells. The concentrations of folate and choline in cells depend on food intake, the absorption of nutrients, and the cellular transport system, which is tissue-specific and developmentally regulated. Relatively few studies have investigated the role of choline transporters in fetal development. CONCLUSIONS: In this review we show relations between functioning of folate and choline transporters and fetal development.

PEMT rs12325817 and PCYT1A rs7639752 polymorphisms are associated with betaine but not choline concentrations in pregnant women.

Maternal metabolism during gestation may depend on nutrient intake but also on polymorphism of genes encoding enzymes involved in metabolism of different nutrients. Data on choline or carnitine metabolism in pregnant women are scarce. We hypothesized that (1) choline intake in Polish pregnant women is inadequate and (2) choline and carnitine metabolism would differ by genotype and nutritional status of pregnant women. One hundred three healthy Polish women aged 18 to 44 years in the third trimester of pregnancy were enrolled in the study. The average choline, folate, and carnitine intakes were 365 ± 14 mg/d, 1089 ± 859 µg, and 132 ± 8 mg/d, respectively. Most women did not achieve an adequate intake of choline. Average choline, betaine, trimethylamine oxide, l-carnitine, and acetylcarnitine concentrations were 10.64 ± 3.30 µmol/L, 14.43 ± 4.01 µmol/L, 2.01 ± 1.24 µmol/L, 12.73 ± 5.41 µmol/L, and 6.79 ± 3.82 µmol/L, respectively. Approximately 15% lower betaine concentrations were observed in the GG homozygotes of PEMT rs12325817 and in the GG homozygotes of PCYT1A rs7639752 than in the respective minor allele carriers. Birth weight was higher in the G allele homozygotes of the CHDH rs2289205 than in the minor allele carriers: GG: 3398 ± 64 g; GA+AA: 3193 ± 76 g. Our study shows that choline intake in Polish pregnant women is inadequate and that polymorphisms of PEMT rs12325817 and PCYT1A rs7639752 are associated with betaine but not choline concentrations.