Negative effects of long-term feeding of high-grain diets to lactating goats on milk fat production and composition by regulating gene expression and DNA methylation in the mammary gland

Abstract Developmental conditions can impact the adult phenotype via epigenetic changes that modulate gene expression. In mammals, methylation of the glucocorticoid receptor gene Nr3c1 has been implicated as mediator of long-term effects of developmental conditions, but this evidence is limited to humans and rodents, and few studies have simultaneously tested for associations between DNA methylation, gene expression and phenotype. Adverse environmental conditions during early life (large natal brood size) or adulthood (high foraging costs) exert multiple long-term phenotypic effects in zebra finches, and we here test for effects of these manipulations on DNA methylation and expression of the Nr3c1 gene in blood. Having been reared in a large brood induced higher DNA methylation of the Nr3c1 regulatory region in adulthood, and this effect persisted over years. Nr3c1 expression was negatively correlated with methylation at 2 out of 8 CpG sites, and was lower in hard foraging conditions, despite foraging conditions having no effect on Nr3c1 methylation at our target region. Nr3c1 expression also correlated with glucocorticoid traits: higher expression level was associated with lower plasma baseline corticosterone concentrations and enhanced corticosterone reactivity. Our results suggest that methylation of the Nr3c1 regulatory region can contribute to the mechanisms underlying the emergence of long-term effects of developmental conditions in birds, but in our system current adversity dominated over early life experiences with respect to receptor expression.

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Expression and nutritional regulation of lipogenic genes in mammary gland and adipose tissues of lactating goats

Journal of Dairy Research ◽

10.1017/s0022029905000786 ◽

2005 ◽

Vol 72 (2) ◽

pp. 250-255 ◽

Cited By ~ 44

Author(s):

Laurence Bernard ◽

Christine Leroux ◽

Muriel Bonnet ◽

Jacques Rouel ◽

Patrice Martin ◽

...

Keyword(s):

Mammary Gland ◽

Milk Fat ◽

De Novo ◽

Lipid Synthesis ◽

Nutritional Regulation ◽

Lipogenic Genes ◽

Lactating Goats ◽

Negative Effect ◽

Few Data ◽

Long Chain

While the effect of long-chain fatty acids on adipose tissue (AT) lipogenic activities has been described in non-lactating ruminants (Vernon, 1977), little is known about their effects on the mammary gland and the AT in lactating animals. However, in cows in mid lactation, duodenal rapeseed oil infusion decreased the rate of fatty acid (FA) synthesis in AT and increased milk yield of long-chain FA (18[ratio ]1, 18[ratio ]2 and 18[ratio ]3) and decreased medium-chain FA (14[ratio ]0 and 16[ratio ]0), suggesting a depressive effect of fat feeding on mammary lipid synthesis de novo (Chilliard et al. 1991). On the other hand, in goat species, the addition of vegetable lipids to the diet led to an increase in the milk fat content and yield (Chilliard et al. 2003) suggesting that the possible negative effect of long-chain FA on FA synthesis in the lactating mammary gland could be more than compensated by increasing the supply of FA brought to the mammary gland for milk synthesis. Elsewhere, AT from various anatomical sites are characterized by different FA composition in goat (Bas et al. 1987) together with different patterns of lipogenic gene expression in sheep (Barber et al. 2000). These results suggest that each AT site is characterized by a specific metabolism. However, in lactating ruminants, few data are available on the extent of expression and regulation of genes coding for lipogenic enzymes in AT. Therefore, the current study was performed in three lipogenic tissues of lactating goats, namely the mammary gland, an internal AT site (perirenal AT) and an external AT site (subcutaneous AT).

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Trans-10, cis-12 conjugated linoleic acid reduces milk fat content and lipogenic gene expression in the mammary gland of sows without altering litter performance

British Journal Of Nutrition ◽

10.1017/s0007114519003325 ◽

2019 ◽

Vol 123 (6) ◽

pp. 610-618 ◽

Cited By ~ 2

Author(s):

E. C. Sandri ◽

K. J. Harvatine ◽

D. E. Oliveira

Keyword(s):

Gene Expression ◽

Mammary Gland ◽

Fatty Acid ◽

Linoleic Acid ◽

Conjugated Linoleic Acid ◽

Milk Fat ◽

Fat Content ◽

Lipogenic Gene ◽

Lipogenic Genes ◽

Lipogenic Gene Expression

AbstractTrans-10, cis-12 conjugated linoleic acid (CLA) decreases milk fat synthesis in lactating sows and involves, at least in part, the down-regulation of lipogenic genes. The objective was to evaluate the effect of CLA on milk composition and lipogenic gene expression. Twenty multiparous sows were randomly assigned to one of the two treatments for 18 d (from day 7 to day 25 of lactation): (1) control (no CLA added) and (2) 1 % of CLA mixed into the ration. CLA treatment decreased milk fat and protein content by 20 % (P = 0·004) and 11 % (P = 0·0001), respectively. However, piglet weight did not differ between treatments (P = 0·60). Dietary CLA increased the concentration of SFA in milk fat by 16 % (P < 0·0001) and decreased MUFA by 17·6 % (P < 0·0001). In the mammary gland, CLA reduced gene expression of acetyl-CoA carboxylase-α by 37 % (P = 0·003), fatty acid synthase by 64 % (P = 0·002), stearoyl-CoA desaturase 1 by 52 % (P = 0·003), lipoprotein lipase by 26 % (P = 0·03), acyl glycerol phosphate acyltransferase 6 by 15 % (P = 0·02) and diacylglycerol acyltransferase 1 by 27 % (P = 0·02), whereas the expression of fatty acid binding protein 3 was not altered by CLA treatment (P = 0·09). Mammary expression of casein-β and α-lactalbumin was reduced by CLA by 68 % (P = 0·0004) and 62 % (P = 0·005), respectively. Additionally, CLA had no effect on the expression of lipogenic genes evaluated in adipose tissue. In summary, CLA reduced milk fat content without negatively affecting litter performance and it affected mammary expression of genes involved in all lipogenic pathways studied.

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Milk fat globule is an alternative to mammary epithelial cells for gene expression analysis in buffalo

Journal of Dairy Research ◽

10.1017/s0022029916000133 ◽

2016 ◽

Vol 83 (2) ◽

pp. 202-208 ◽

Cited By ~ 12

Author(s):

Qiuming Chen ◽

Yanjun Wu ◽

Mingyuan Zhang ◽

Wenwen Xu ◽

Xiaoping Guo ◽

...

Keyword(s):

Gene Expression ◽

Mammary Gland ◽

Epithelial Cells ◽

Expression Analysis ◽

Milk Fat ◽

Gene Expression Analysis ◽

Mammary Epithelial Cells ◽

Mammary Epithelial ◽

Milk Fat Globule ◽

Fat Globule

Owing to the difficulty in obtaining mammary gland tissue from lactating animals, it is difficult to test the expression levels of genes in mammary gland. The aim of the current study was to identify if milk fat globule (MFG) in buffalo milk was an alternative to mammary gland (MG) and milk somatic cell (MSC) for gene expression analysis. Six buffalos in late lactation were selected to collect MFG and MSC, and then MG was obtained by surgery. MFG was stained with acridine orange to successfully visualise RNA and several cytoplasmic crescents in MFG. The total RNA in MFG was successfully isolated and the integrity was assessed by agarose gel electrophoresis. We analysed the cellular components in MFG, MG and MSC through testing the expression of cell-specific genes by qRT-PCR. The results showed that adipocyte-specific gene (AdipoQ) and leucocyte-specific genes (CD43, CSF1 and IL1α) in MFG were not detected, whereas epithelial cell marker genes (Keratin 8 and Keratin 18) in MFG were higher than in MSC and lower than in MG, fibroblast marker gene (vimentin) in MFG was significantly lower than in MG and MSC, milk protein genes (LALBA, BLG and CSN2) and milk fat synthesis-related genes (ACC, BTN1A1, FABP3 and FAS) in MFG were higher than in MG and MSC. In conclusion, the total RNA in MFG mainly derives from mammary epithelial cells and can be used to study the functional gene expression of mammary epithelial cells.

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Sleep deprivation and diet affect human GH gene expression in transgenic mice in vivo

Endocrine Connections ◽

10.1530/ec-20-0354 ◽

2020 ◽

Vol 9 (12) ◽

pp. 1135-1147

Author(s):

Jessica S Jarmasz ◽

Yan Jin ◽

Hana Vakili ◽

Peter A Cattini

Keyword(s):

Gene Expression ◽

Dna Methylation ◽

Sleep Deprivation ◽

Chow Diet ◽

Negative Effects ◽

Production Studies ◽

First Time ◽

Rna Levels

Human (h) growth hormone (GH) production studies are largely limited to effects on secretion. How pituitary hGH gene (hGH-N/GH1) expression is regulated is important in our understanding of the role hGH plays in physiology and disease. Here we assess for the first time the effect of sleep deprivation (SD) and high-fat diet (HFD) on hGH-N expression in vivo using partially humanized 171hGH/CS transgenic (TG) mice, and attempted to elucidate a role for DNA methylation. Activation of hGH-N expression requires interactions between promoter and upstream locus control region (LCR) sequences including pituitary-specific hypersensitive site (HS) I/II. Both SD and diet affect hGH secretion, but the effect of SD on hGH-N expression is unknown. Mice fed a HFD or regular chow diet for 3 days underwent SD (or no SD) for 6 h at Zeitgeber time (ZT) 3. Serum and pituitaries were assessed over 24 h at 6-h intervals beginning at ZT 14. SD and HFD caused significant changes in serum corticosterone and insulin, as well as hGH and circadian clock-related gene RNA levels. No clear association between DNA methylation and the negative effects of SD or diet on hGH RNA levels was observed. However, a correlation with increased methylation at a CpG (cytosine paired with a guanine) in a putative E-box within the hGH LCR HS II was suggested in situ. Methylation at this site also increased BMAL1/CLOCK-related nuclear protein binding in vitro. These observations support an effect of SD on hGH synthesis at the level of gene expression.

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