Maternal low protein diet and fetal programming of lean type 2 diabetes

Maternal nutrition is found to be the key factor that determines fetal health in utero and metabolic health during adulthood.Metabolic diseases have been primarily attributed to impaired maternal nutrition during pregnancy,and impaired nutrition has been an immense issue across the globe.In recent years,type 2 diabetes(T2D)has reached epidemic proportion and is a severe public health problem in many countries.Although plenty of research has already been conducted to tackle T2D which is associated with obesity,little is known regarding the etiology and pathophysiology of lean T2D,a variant of T2D.Recent studies have focused on the effects of epigenetic variation on the contribution of in utero origins of lean T2D,although other mechanisms might also contribute to the pathology.Observational studies in humans and experiments in animals strongly suggest an association between maternal low protein diet and lean T2D phenotype.In addition,clear sex-specific disease prevalence was observed in different studies.Consequently,more research is essential for the understanding of the etiology and pathophysiology of lean T2D,which might help to develop better disease prevention and treatment strategies.This review examines the role of protein insufficiency in the maternal diet as the central driver of the developmental programming of lean T2D.

Stage-specific nutritional management and developmental programming to optimize meat production

Over the past few decades,genetic selection and refined nutritional management have extensively been used to increase the growth rate and lean meat production of livestock.However,the rapid growth rates of modern breeds are often accompanied by a reduction in intramuscular fat deposition and increased occurrences of muscle abnor‑malities,impairing meat quality and processing functionality.Early stages of animal development set the long‑term growth trajectory of offspring.However,due to the seasonal reproductive cycles of ruminant livestock,gestational nutrient deficiencies caused by seasonal variations,frequent droughts,and unfavorable geological locations nega‑tively affect fetal development and their subsequent production efficiency and meat quality.Therefore,enrolling live‑stock in nutritional intervention strategies during gestation is effective for improving the body composition and meat quality of the offspring at harvest.These crucial early developmental stages include embryonic,fetal,and postnatal stages,which have stage‑specific effects on subsequent offspring development,body composition,and meat quality.This review summarizes contemporary research in the embryonic,fetal,and neonatal development,and the impacts of maternal nutrition on the early development and programming effects on the long‑term growth performance of livestock.Understanding the developmental and metabolic characteristics of skeletal muscle,adipose,and fibrotic tissues will facilitate the development of stage‑specific nutritional management strategies to optimize production efficiency and meat quality.

Paternal physical exercise modulates global DNA methylation status in the hippocampus of male rat offspring

It is widely known that maternal physical exercise is able to induce beneficial improvements in offspring cognition; however, the effects of paternal exercise have not been explored in detail. The present study was designed to evaluate the impact of paternal physical exercise on memory and learning, neuroplasticity and DNA methylation levels in the hippocampus of male offspring. Adult male Wistar rats were divided into two groups: sedentary or exercised fathers. The paternal preconception exercise protocol consisted of treadmill running, 20 minutes daily, 5 consecutive days per week for 22 days, while the mothers were not trained. After mating, paternal sperm was collected for global DNA methylation analysis. At postnatal day 53, the offspring were euthanized, and the hippocampus was dissected to measure cell survival by 5-bromo-2′-deoxiuridine and to determine the expression of synaptophysin, reelin, brain-derived neurotrophic factor and global DNA methylation levels. To measure spatial memory and learning changes in offspring, the Morris water maze paradigm was used. There was an improvement in spatial learning, as well as a significant decrease in hippocampal global DNA methylation levels in the offspring from exercised fathers compared with those from sedentary ones; however, no changes were observed in neuroplasticity biomarkers brain-derived neurotrophic factor, reelin and 5-bromo-2′-deoxiuridine. Finally, the global DNA methylation of paternal sperm was not significantly changed by physical exercise. These results suggest a link between paternal preconception physical activity and cognitive benefit, which may be associated with hippocampal epigenetic programming in male offspring. However, the biological mechanisms of this modulation remain unclear.

Effects of supplements differing in fatty acid profile to late gestational beef cows on cow performance,calf growth performance,and mRNA expression of genes associated with myogenesis and adipogenesis

Background:Maternal nutrition during gestation affects fetal development,which has long-term programming effects on offspring postnatal growth performance.With a critical role in protein and lipid metabolism,essential fatty acids can influence the development of muscle and adipose tissue.The experiment investigated the effects of late gestation supplements(77 d prepartum),either rich in saturated and monounsaturated fatty acids(CON;155 g/cow/d EnerGII)or polyunsaturated fatty acids(PUFA;80 g/cow/d Strata and 80 g/cow/d Prequel),on cow performance and subsequent calf growth performance as well as mRNA expression in longissimus muscle(LM)and subcutaneous adipose tissue at birth and weaning.Results:There was no difference(P≥0.34)in cow body weight(BW)or body condition score from presupplementation through weaning.Relative concentrations of C18:3n-3 and C20:4n-6 decreased(P≤0.05)to a greater extent from mid-supplementation to calving for PUFA compared with CON cows.Cow plasma C20:0,C20:5n-3,and C22:6n-3 were increased(P≤0.01)in PUFA during supplementation period.At birth,PUFA steers had greater(P=0.01)plasma C20:5n-3.No differences(P≥0.33)were detected in steer birth BW or dam milk production,however,CON steers tended(P=0.06)to have greater pre-weaning average daily gain and had greater(P=0.05)weaning BW compared with PUFA.For mRNA expression in steers:MYH7 and C/EBPβin LM increased(P≤0.04)to a greater extent from birth to weaning for PUFA compared with CON;MYF5 in LM and C/EBPβin adipose tissue tended(P≤0.08)to decrease more from birth to weaning for CON compared with PUFA;SCD in PUFA adipose tissue tended(P=0.08)to decrease to a greater extent from birth to weaning than CON.In addition,maternal PUFA supplementation tended(P=0.08)to decrease MYOG mRNA expression in LM and decreased(P=0.02)ZFP423 in adipose tissue during the pre-weaning stage.Conclusions:Late gestation PUFA supplementation decreased pre-weaning growth performance of the subsequent steer progeny compared with CON supplementation,which could have been a result of downregulated mRNA expression of myogenic genes during pre-weaning period.

Effect of gestational protein restriction on left ventricle hypertrophy and heart angiotensin II signaling pathway in adult offspring rats

Maternal protein restriction may be a risk factor for cardiovascular disorders in adulthood. The RAS (renin-angiotensin-system) plays a pivotal role in cardiac remodeling. Components of the RAS, including angiotensin II (AngII) and its receptors type 1 (AT1R) and 2 (AT2R) are expressed in the heart. This study investigates whether gestational protein restriction alters the expression and localization of AT1R and AT2R and RAS signaling pathway proteins in parallel with left ventricle hypertrophy and systemic hypertension in male offspring. Dams were kept on normal (NP, 17% protein) or low (LP, 6% protein) protein diet during pregnancy. Systolic blood pressure (SBP) of male offspring was measured from the 8th to 16th week and left ventricles of 16-wk-old rats were processed for histology, morphometric, immunoblotting and immunohistochemistry. LP offspring showed a significant reduction in birth body weight and SBP increased significantly from the 8th week. Left ventricle mass and cardiomyocytes area were also significantly higher in LP animals. Widespread perivascular fibrosis was not detected in the heart tissue. Analysis by immunoblotting and immunohistochemistry demonstrated a significant enhance in cardiomyocyte expression of AT1R and ERK1 in LP offspring. Expression of PI3K in LP was significantly reduced in cardiomyocytes and in the intramural coronary wall, while AT2R expression was unchanged in the NP group. We also found reduced LP expression of JAK2 and STAT3. In conclusion, our data also suggest that changes in the RAS may play a role in the ventricular growth through upregulation of the AT1-mediated ERK1/2 response, despite unchanged AT2R expression.

MicroRNAs： crucial modulators of fetal epigenetic programming in nutrition and glucose metabolism

It is generally believed that genotype and adult lifestyle elements are primary risks of diabetes mellitus. However, increasing evidence demonstrates that early life malnutrition during the period of gestation and/or lactation may increase our susceptibility to some metabolic diseases in later life and the underlying mechanism is not very clear. Recently, epigenetics is hypothesized to be the important molecular basis of the imbalanced early life nutrition and glucose metabolism disorders. The fundamental mechanism is that early developmental nutrition can regulate epigenetic modifications of some genes associated with development and metabolism. MicroRNAs （miRNAs） are recognized as an important epigenetic modification and they are a major class of small noncoding RNAs （about 20-22 nucleotides） which can mediate posttranscriptional regulation of target genes with cell differentiation and apoptosis. Recent studies suggest that miRNAs may be the crucial modulators of fetal epigenetic programming in nutrition and metabolic disorders. How miRNAs can modulate the relationship between early life nutrition and disease susceptibilities, especially for aberrant glucose metabolism？

Effects of maternal dietary omega-3 polyunsaturated fatty acids and methionine during late gestation on fetal growth,DNA methylation,and mRNA relative expression of genes associated with the inflammatory response,lipid metabolism and DNA methylation in placenta and offspring’s liver in sheep

Background:Omega-3 PUFA or methionine(Met)supply during gestation alters offspring physiology.However,the effect of both nutrients on fetal development has not been explored.Our objective was to determine the effects of supplementation of these two nutrients during late gestation on fetal growth,DNA methylation,and mRNA expression of genes associated with the inflammatory response,and DNA methylation.Ewes(n=5/treatment)were fed from day 100 to 145 of gestation one of the following treatments:1)basal diet(NS)without fatty acids(FS)or methionine(MS)supplementation;2)FS(10 g/kg Ca salts,source omega-3 PUFA);3)MS(1 g/kg rumen protected methionine);and 4)FS and MS(FS-MS).On day 145,ewes were euthanized,and data from dams and fetus was recorded.Placenta(cotyledon),fetal liver,and blood samples were collected.Results:A treatments interaction on fetal liver weight,ewe body weight and body condition score(BCS)was observed;FS-MS were heavier(P<0.01)than FS and MS,and FS-MS ewes had a better(P=0.02)BCS than NS.Methionine increased(P=0.03)ewe plasma glucose concentration.Fetal liver global DNA methylation increased(P<0.01)in FS and MS.Dietary treatments modify the mRNA relative expression on some of the genes evaluated.In the fetal liver,FS increased(P=0.04)the mRNA relative expression of arachidonate-5-lipoxygenase-activatingprotein and tended to decrease(P=0.06)methionine-adenosyltransferase-1A.Moreover,MS decreased(P=0.04)DNA-methyltransferase-1 and tended to decrease(P=0.08)free-fatty-acid-receptor-1 mRNA relative expression.Furthermore,FS-MS decreased mRNA relative expression of tumor-necrosis-factor-alpha(P=0.05),peroxisomeproliferator-activated-receptor-delta(P=0.03)and gamma(P=0.04),tended to decrease(P≤0.09)interleukin-6,fatty-acid-transport-protein-1,and delta-5-desaturase,and increased adenosylhomocysteinase(P=0.04)mRNA relative expression.In cotyledon,FS tended to decrease fatty acid binding protein 4(P=0.09)mRNA relative expression.Conclusion:Omega-3 PUFA and Met supplementation improves dam’s performance in late gestation,which was positively correlated with an increase in offspring’s liver development.Moreover,FS-MS decreased mRNA relative expression of proinflammatory cytokines,and lipogenic genes,and increased the expression on an enzyme that has an important role in methylation.

Cardioprotective and renoprotective effects of Cocos nucifera water in offspring of high fat diet fed Wistar rat dams

Objective:To evaluate the effects of Cocos nucifera(C.nucifera)water on the cardiovascular and renal functions of offspring from rat dams fed high fat diet during gestation.Methods:Four groups of pregnant Wistar rats were treated from gestation day 1 to 21;namely,control(1 mL/100 g distilled water),C.nucifera water(1 mL/100 g C.nucifera water),high fat diet(1 mL/100 g distilled water+30%butter:70%standard rodent diet)and high fat diet+C.nucifera water(1 mL/100 g C.nucifera water+30%butter:70%standard rodent diet).All dams received standard rodent diet from gestation day 22,and offspring were weaned to standard rodent diet on postnatal day 28.On postnatal day 120,serum and cardiac levels of malondialdehyde,interleukin-1βand high sensitivity C-reactive protein were determined in offspring.Serum creatinine and urea levels as well as histology of heart and kidney tissue were assessed.Data were analyzed using One-way ANOVA and P<0.05 was considered statistically significant.Results:Male high fat diet offspring showed significantly increased(P<0.05)serum interleukin-1βcompared with C.nucifera water offspring.The increase in serum high sensitivity C-reactive protein observed in female high fat diet offspring was not present in high fat diet+C.nucifera water offspring.Heart tissues from high fat diet offspring showed scanty fibers and congested myocardium with mild fibrosis.Male high fat diet offspring kidneys showed mesangial cell hyperplasia,fat infiltration and mild tubular necrosis.These were accompanied with alterations in serum urea and creatinine levels in high fat diet+C.nucifera water offspring.Conclusions:C.nucifera water exerts cardioprotective and renoprotective effects on offspring of rat dams fed high fat diet during gestation via an anti-inflammatory mechanism.