Lipid Metabolism In Offspring Research Articles

Supplementation of Maternal Diets with Choline, B‐vitamin and Docosahexaenoic Acid (DHA) Alters Gene Expressions Associated with Hepatic Lipid Metabolism in Offspring

This study was to explore whether maternal supplementation of choline with supporting b-vitamins and DHA during malnourishment influences fetal expression of RNAs involved in hepatic lipid metabolism. Pregnant gilts (n=24) were randomly assigned to full-fed control (no feed intake restriction) or global nutrient restricted (GNR, 50-70% feed intake restriction) groups. The GNR gilts received supplementation of choline and supporting b-vitamins and/or DHA according to a 2 x 2 factorial arrangement. Piglets were delivered by C-section on d 110 ± 2 and fetal liver samples were collected. RNA was extracted, and miRNA and mRNA libraries were constructed and sequenced by using Ion Proton Sequencing Platform. Results showed that abundance of miR-21, miR-122, miR-145, miR-103, miR-221, miR490-3p and miR-375 associated with regulation of hepatic lipid metabolism were modified in offspring from GNR gilts as compared with offspring from control gilts. The modifications in these miRNAs were affected by maternal supplementation of choline or/and DHA. Additionally, the expressions of HMGCS2, FABP1, FABP2, AACS, CHKA, GPCPD1, LPCAT3, AGPAT6, SCD, ELOVL7, ELOVL6, PTGS1 and LRAT significantly differed between offspring from control and GNR gilts. Supplementation of choline or/and DHA modified gene expressions of PPARα, RXR2, HMGCS2, FABP2, SERBF2, CHKA, AGPAT6, SCD, ELOVL7, ELOVL6 and PTGS. These results strongly suggest that maternal choline and DHA play important roles in programming of fetal lipid metabolism during development via regulation of gene expression. Supported by Bill & Melinda Gates Foundation, GCE OPP1061037.

Regulation of immune tolerance during pregnancy

s / Placenta 36 (2015) 469e521 478 lead to hepatic dysfunction and impair proper detoxification of the organism in fetuses and offspring. Liver leptin resistance on lipid catabolism begins in utero and may be responsible for the alterations on the offspring's lipid metabolism impairments leading to liver lipotoxicity. S6. REGULATION OF IMMUNE TOLERANCE DURING PREGNANCY Anne Schumacher, Franziska Fettke, Nicole Meyer, Stefanie Langwisch, Stefan Fest, Ana Claudia Zenclussen. Experimental Obstetrics and Gynecology, Medical Faculty, Otto-von-Guericke University Magdeburg,

Effects of Maternal Dietary Energy Restriction on Fat Deposition of Offspring

The study was carried out to investigate the effects of maternal dietary energy restriction on growth performance, serum indices and fat deposition of offspring. A total of 400 female Arbor Acres (AA) broiler breeders were studied. These female birds involved three experimental treatments and a control group with normal dietary energy diets (ND, 11.7 MJ of ME • kg−1 during the laying). In treatments 2, 3 and 4, the energies of diets were 20%, 30% and 50% (LD20, LD30 and LD50) lower than those of the control, respectively. The study commenced at the beginning of the laying period when the total egg production reached 5% of the flock. All the broiler offspring were fed the same diets. The results showed that in low energy diets, offspring showed decreased 1-day-old weight, but 49-day-old weight was higher in LD20 diet (P<0.05). For offspring during days 1-49, the average daily gain (ADG) in LD20 group and the feed conversion ratio in LD50 group were improved as compared with those of the control (P<0.05). Compared with the control, abdominal fat percentage increased in 49-day-old offspring from LD30 diet (P<0.05); the fat content of breast muscle in offspring increased in broilers fed low energy diets (P<0.05). In 28-day-old offspring from breeders given LD20 and LD50 diets, liver fat percentages were higher compared with ND (P<0.05). The subcutaneous fat thickness in 28-day-old offspring from LD50 group and 49-day-old offspring from LD30 group was higher (P<0.05). On day 49, the serum cholesterol (CHO) of offspring from breeders fed LD20 diet and serum high-density lipoprotein (HDL) of offspring from breeders fed LD50 diet reduced compared with those of the control (P<0.05). In addition, a higher triiodothyronine (T3) content in serum was found in offspring from broiler breeders given LD20 and LD30 diets (P<0.05). Serum thyroxine (T4) in offspring significantly decreased with the decrease of diet energy (P<0.05). In conclusion, to a certain extent, dietary energy restriction in breeders could improve growth performance and promote lipid metabolism of offspring.

Maternal high-fat diet consumption modulates hepatic lipid metabolism and microRNA-122 (miR-122) and microRNA-370 (miR-370) expression in offspring

Maternal consumption of a high-fat diet (HFD) during pregnancy and lactation is closely related to hepatic lipid accumulation, insulin resistance and increased serum cytokine levels in offspring and into their adulthood. MicroRNA (miRNA) have been implicated in cholesterol biosynthesis and fatty acid metabolism. We evaluated the modulation of hepatic fatty acid synthesis (de novo), β-oxidation pathways, and miRNA-122 (miR-122) and miRNA-370 (miR-370) expression in recently weaned offspring (day 28) of mouse dams fed a HFD (HFD-O) or a standard chow (SC-O) during pregnancy and lactation. Compared with SC-O mice, HFD-O mice weighed more, had a larger adipose tissue mass and were more intolerant to glucose and insulin (P< 0·05). HFD-O mice also presented more levels of serum cholesterol, TAG, NEFA and hepatic IκB kinase and c-Jun N-terminal kinase phosphorylation compared with SC-O mice (P< 0·05). Protein levels of fatty acid synthase, acetyl-CoA carboxylase and 3-hydroxy-3-methylglutaryl-CoA reductase were similar in HFD-O and SC-O mice, whereas expression levels of SCD1 mRNA and protein were more abundant in HFD-O mice than in SC-O mice (P< 0·05). Interestingly, mRNA expression levels of the β-oxidation-related genes ACADVL and CPT1 were decreased in HFD-O mice (P< 0·05). Furthermore, the expression of miR-122 was reduced but that of miR-370 was increased in HFD-O mice compared with that in SC-O mice (P< 0·05). Changes in hepatic lipid metabolism were accompanied by increased mRNA content of AGPAT1 and TAG deposition in HFD-O mice (P< 0·05). Taken together, the present results strongly suggest that maternal consumption of a HFD affects the early lipid metabolism of offspring by modulating the expression of hepatic β-oxidation-related genes and miRNA that can contribute to metabolic disturbances in adult life.

Effects of Japanese Food Typical of That Consumed during Different Periods in the Past on Breast Milk-mediated Lipid Metabolism in Offspring

Effects of Japanese Food Typical of That Consumed during Different Periods in the Past on Breast Milk-mediated Lipid Metabolism in Offspring

Alteration of fatty acid metabolism in the liver, adipose tissue, and testis of male mice conceived through assisted reproductive technologies: fatty acid metabolism in ART mice

BackgroundLipid metabolism plays important roles in the whole process of pregnancy. Previous studies have demonstrated abnormalities of lipid metabolism in the placentas of pregnancies obtained by assisted reproductive technology (ART). Therefore, we hypothesized that ART micromanipulation may affect lipid metabolism in offspring, and focused on the fatty acid metabolism in ART male offspring in this study.MethodsThe fatty acid metabolism in the liver, adipose tissue and testis was detected. The comparison between naturally conceived (NC), controlled ovarian hyperstimulation (COH), in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI) mice was made to analyze the effect of ART on offspring. The mice models in this study included two age groups: adult group and old group. The fatty acid composition and the expression of lipid metabolism-related genes were analyzed by GC-MS and qRT-PCR.ResultsThe fatty acid composition in the liver and adipose tissue were significantly altered in ART mice, but no significant difference was found in the testis. In adipose tissue, ART mice showed decreased monounsaturated fatty acids (MUFAs) and increased polyunsaturated fatty acids (PUFAs) in both adult and old mice, while the alteration of saturated fatty acids (SFAs) in the adult disappeared in the old. In liver, the changes were much complex in adult mice, while increased MUFAs and decreased PUFAs were found in ART old mice. The activities of fatty acid metabolism-related enzymes and the expression of lipogenic and lipolytic proteins changed in ART groups, with the adult mice and old mice showing inconsistent alterations. Further analysis indicated that SFAs was closely associated with the alterations of fatty acid metabolism-related enzyme activities and the expression of lipogenic and lipolytic proteins. Furthermore, we also found that the effect of separated ART treatments on fatty acid metabolism varied with different ages and tissues.ConclusionsART treatments had effect on the fatty acid composition in adipose tissue and liver of male mice. The alteration of SFAs content was crucial for the regulation of fatty acid composition. These changes might have potential effects on the health of ART male offspring which need further investigation.

Azuki bean polyphenols intake during lactation upregulate AMPK in male rat offspring exposed to fetal malnutrition

ObjectiveFetal malnutrition is an early-life inducer of dyslipidemia and glucose intolerance. The aim of this study was to examine whether maternal azuki bean (Vigna angularis) polyphenol (AP) intake during lactation affects the adenosine monophosphate–activated protein kinase (AMPK) pathway and lipid metabolism in offspring exposed to fetal malnutrition. MethodsPregnant Wistar rats were divided into three groups: a control diet offered during gestation and lactation (CC), a low-protein diet during gestation and a control diet during lactation (LPC); and a low-protein diet during gestation and a 1.0% AP-containing control diet during lactation (LPAP). Male pups were randomly selected for the study; half the pups were sacrificed at 3 wk of age and the other half were fed a standard diet and sacrificed at 23 wk. Hepatic triacylglycerol levels, phosphorylation levels of AMPK and acetyl-coenzyme A carboxylase (ACC), and mRNA levels of sterol regulatory element-binding protein-1c (SREBP-1c) were evaluated. ResultsSignificant decreases in body weights and hepatic triacylglycerol levels were found in the LPAP compared with the LPC group. Plasma adiponectin levels in the LPAP group were higher than those in the LPC group. AMPK phosphorylation was upregulated in the livers and skeletal muscles in young and adult LPAP compared with LPC rats. ACC phosphorylation was upregulated in skeletal muscles of LPAP rats. SREBP-1c mRNA expression was decreased in the livers of LPAP rats. ConclusionOur results suggest that maternal AP intake during lactation upregulates AMPK phosphorylation not only in young but also in adult offspring exposed to fetal malnutrition and may lead to decreased hepatic lipid accumulation by ACC phosphorylation and downregulation of SREBP-1c expression.

MicroRNA-130b and microRNA-374b mediate the effect of maternal dietary protein on offspring lipid metabolism in Meishan pigs

To investigate whether the effect of maternal dietary protein on offspring lipid metabolism is mediated by microRNA (miRNA), fourteen Meishan sows were fed either low-protein (LP, half of standard protein (SP) level, n 7) or SP (n 7) diets throughout gestation and lactation periods. PPAR-γ and CCAAT/enhancer-binding protein-β (C/EBP-β) protein expression was evaluated. The expression of miRNA predicted to directly target PPAR-γ and C/EBP-β in the subcutaneous fat of offspring at weaning age was determined, and the functions of these potential miRNA were verified. The results showed that piglet body weight and back fat thickness were significantly decreased in the LP group compared with the SP group (P<0·05). The protein level of PPAR-γ was significantly decreased and C/EBP-β protein expression was also decreased, though not significantly (P=0·056), in the subcutaneous fat of the LP group. Furthermore, miRNA expression analysis showed that miR-130b, targeting the PPAR-γ 3'-untranslated region (UTR), and miR-374b, targeting the C/EBP-β 3'-UTR, were significantly increased in the LP group compared with the SP group; other candidate regulatory miRNA were expressed similarly in both groups. Dual luciferase activity assay results indicated that miR-130b directly recognised and bound to the 3'-UTR of PPAR-γ and thereby suppressed PPAR-γ gene expression. Similar results were found for miR-374b and the 3'-UTR of C/EBP-β. The present study showed that miR-130b and miR-374b are involved in the effect of maternal dietary protein on offspring lipid metabolism in pigs. These results shed new light on our understanding of the maternal effect on offspring lipid deposition.

Maternal micronutrient restriction programs the body adiposity, adipocyte function and lipid metabolism in offspring: A review

Fetal growth is a complex process which depends both on the genetic makeup and intrauterine environment. Maternal nutrition during pregnancy is an important determinant of fetal growth. Adequate nutrient supply is required during pregnancy and lactation for the support of fetal/infant growth and development. Macro- and micronutrients are both important to sustain pregnancy and for appropriate growth of the fetus. While macronutrients provide energy and proteins for fetal growth, micronutrients play a major role in the metabolism of macronutrients, structural and cellular metabolism of the fetus. Discrepancies in maternal diet at different stages of foetal growth / offspring development can have pronounced influences on the health and well-being of the offspring. Indeed intrauterine growth restriction induced by nutrient insult can irreversibly modulate the endocrine/metabolic status of the fetus that leads to the development of adiposity and insulin resistance in its later life. Understanding the role of micronutrients during the development of fetus will provide insights into the probable underlying / associated mechanisms in the metabolic pathways of endocrine related complications. Keeping in view the modernized lifestyle and food habits that lead to the development of adiposity and world burden of obesity, this review focuses mainly on the role of maternal micronutrients in the foetal origins of adiposity.

Effects of maternal consumption of low‐protein diet with soy as protein source on hepatic glucose and lipid metabolism of the rat offspring

Maternal protein restriction (PR) induces dyslipidemia and impaired glucose homeostasis in offspring, which is associated with metabolic disease development in later life. Recent studies showed that maternal soy protein diet improves insulin sensitivity and lipid profile of offspring. Therefore, we investigated effects of maternal PR diet with soy as protein source on hepatic glucose and lipid metabolism in offspring. SD rats were fed 20% casein, 20% isoflavone‐poor soy protein isolate (SPI) or 10% SPI during pregnancy and lactation. Male offspring was studied at postnatal d21. Body weight and relative liver weight were significantly lower in offspring of dam fed 10% SPI diet (10% SPI). Serum glucose, triglyceride (TG), insulin concentrations and HOMA‐IR were significantly lower in 20% SPI compared to those in 20% casein. SPI level did not significantly change serum glucose concentration and HOMA‐IR. Serum and hepatic TG concentrations were significantly lower in 10% SPI compared to those in 20% SPI. Hepatic mRNA expression of peroxisome proliferator‐activated receptor alpha, a transcription factor involved in the regulation of glucose and lipid homeostasis, was not significantly different among groups. Therefore, these findings indicate that maternal consumption of soy protein may alleviate the PR‐mediated metabolic disease development in rat offspring. Supported by Korea Research Foundation.

Maternal consumption of high-prebiotic fibre or -protein diets during pregnancy and lactation differentially influences satiety hormones and expression of genes involved in glucose and lipid metabolism in offspring in rats

Risk of developing the metabolic syndrome may be influenced by nutritional environment early in life. We examined the effects of high-fibre (HF) and high-protein (HP) diets consumed during pregnancy and lactation on satiety hormones and expression of genes involved in glucose and lipid metabolism in offspring. Wistar dams were fed a control (C), HF or HP diets during pregnancy and lactation. At parturition, litters were culled to ten pups. At 21 d, all pups were weaned onto C diet. At 7, 14, 21, 28 and 35 d after birth, blood was analysed for satiety hormones and tissues for mRNA expression in offspring. No differences were observed in litter size or birth weight. At 21 d, offspring of HF dams had greater adjusted intestinal mass and lower liver weight than those of C but not of HP dams. Plasma glucose at 28 d and amylin at 7, 14 and 28 d were lower in HF v. C and HP offspring. Glucagon-like peptide-1 was higher in HP offspring than in HF offspring at 7 d but was higher in HF v. C offspring at 21 d. Offspring of HF dams had higher glucose transporter (GLUT2 and Na+-dependent glucose/galactose transporter) mRNA expression at 21 d v. C and HP offspring. In brown adipose tissue, HF and HP up-regulated uncoupling protein-1 and PPAR-γ coactivator. HP was associated with increased resistin and IL-6 mRNA expression. The present study demonstrates that maternal diet composition differentially regulates circulating satiety hormones and genes involved in glucose transport and energy metabolism in offspring. These early changes could have long-term consequences for obesity risk.

Paternally Induced Transgenerational Environmental Reprogramming of Metabolic Gene Expression in Mammals

Epigenetic information can be inherited through the mammalian germline and represents a plausible transgenerational carrier of environmental information. To test whether transgenerational inheritance of environmental information occurs in mammals, we carried out an expression profiling screen for genes inmice that responded to paternal diet. Offspring ofmales fed a low-protein diet exhibited elevated hepatic expression of many genes involved in lipid and cholesterol biosynthesis and decreased levels of cholesterol esters, relative to the offspring of males fed a control diet. Epigenomic profiling of offspring livers revealed numerous modest (∼20%) changes in cytosine methylation depending on paternal diet, including reproducible changes in methylation over a likely enhancer for the key lipid regulator Ppara. These results, in conjunction with recent human epidemiological data, indicate that parental diet can affect cholesterol and lipid metabolism in offspring and define a model system to study environmental reprogramming of the heritable epigenome.

High-unsaturated-fat, high-protein, and low-carbohydrate diet during pregnancy and lactation modulates hepatic lipid metabolism in female adult offspring.

Whether a high-unsaturated-fat, high-protein (HFP), and low-carbohydrate (CHO) diet during gestation has long-lasting beneficial effects on lipid metabolism in the offspring was investigated using a mouse model. Female mice were fed either a standard (CHO rich) chow diet or a CHO HFP diet, before and during gestation and lactation. All offspring were weaned onto the same chow until adulthood. Although liver cholesterol concentration and fasting plasma triglyceride (TG), cholesterol, and free fatty acid concentrations were not affected in either male or female HFP offspring, hepatic TG concentration was reduced by approximately 51% (P < 0.05) in the female adult offspring from dams on the HFP diet, compared with females from dams on the chow diet (a trend toward reduced TG concentration was also observed in the male). Furthermore, hepatic protein levels for CD36, carnitine palmitoyltransferase-1 (CPT-1), and peroxisomal proliferator activated receptor-alpha (PPAR-alpha) were increased by approximately 46% (P < 0.001), approximately 52% (P < 0.001), and approximately 14% (P = 0.035), respectively, in the female HFP offspring. Liver TG levels were negatively correlated with protein levels of CD 36 (r = -0.69, P = 0.007), CPT-1 (r = -0.55, P = 0.033), and PPAR-alpha (r = -0.57, P = 0.025) in these offspring. In conclusion, a maternal HFP diet during gestation and lactation reduces hepatic TG concentration in female offspring, which is linked with increased protein levels in fatty acid oxidation.