Dataset Information

Trans-10, cis 12-Conjugated Linoleic Acid-Induced Milk Fat Depression Is Associated with Inhibition of PPAR? Signaling and Inflammation in Murine Mammary Tissue.

ABSTRACT: Exogenous trans-10, cis-12-CLA (CLA) reduces lipid synthesis in murine adipose and mammary (MG) tissues. However, genomewide alterations in MG and liver (LIV) associated with dietary CLA during lactation remain unknown. We fed mice (n = 5/diet) control or control?+?trans-10, cis-12-CLA (37?mg/day) between d 6 and d 10 postpartum. The 35,302 annotated murine exonic evidence-based oligo (MEEBO) microarray and quantitative RT-PCR were used for transcript profiling. Milk fat concentration was 44% lower on d 10 versus d 6 due to CLA. The CLA diet resulted in differential expression of 1,496 genes. Bioinformatics analyses underscored that a major effect of CLA on MG encompassed alterations in cellular signaling pathways and phospholipid species biosynthesis. Dietary CLA induced genes related to ER stress (Xbp1), apoptosis (Bcl2), and inflammation (Orm1, Saa2, and Cp). It also induced marked inhibition of PPAR ? signaling, including downregulation of Pparg and Srebf1 and several lipogenic target genes (Scd, Fasn, and Gpam). In LIV, CLA induced hepatic steatosis probably through perturbations in the mitochondrial functions and induction of ER stress. Overall, results from this study underscored the role of PPAR ? signaling on mammary lipogenic target regulation. The proinflammatory effect due to CLA could be related to inhibition of PPAR ? signaling.

SUBMITTER: Kadegowda AK

PROVIDER: S-EPMC3666273 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature

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Trans-10, cis 12-Conjugated Linoleic Acid-Induced Milk Fat Depression Is Associated with Inhibition of PPARγ Signaling and Inflammation in Murine Mammary Tissue.

Kadegowda Anil K G AK Khan M Jawad MJ Piperova Liliana S LS Teter Beverly B BB Rodriguez-Zas Sandra L SL Erdman Richard A RA Loor Juan J JJ

Journal of lipids 20130514

Exogenous trans-10, cis-12-CLA (CLA) reduces lipid synthesis in murine adipose and mammary (MG) tissues. However, genomewide alterations in MG and liver (LIV) associated with dietary CLA during lactation remain unknown. We fed mice (n = 5/diet) control or control + trans-10, cis-12-CLA (37 mg/day) between d 6 and d 10 postpartum. The 35,302 annotated murine exonic evidence-based oligo (MEEBO) microarray and quantitative RT-PCR were used for transcript profiling. Milk fat concentration was 44% lo ...[more]

PMID: 23762566

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Project description:Background:Starch is an important substance that supplies energy to ruminants. To provide sufficient energy for high-yielding dairy ruminants, they are typically fed starch-enriched diets. However, starch-enriched diets have been proven to increase the risk of milk fat depression (MFD) in dairy cows. The starch present in ruminant diets could be divided into rumen-degradable starch (RDS) and rumen escaped starch (RES) according to their different degradation sites (rumen or intestine). Goats and cows have different sensitivities to MFD. Data regarding the potential roles of RDS in milk fat synthesis in the mammary tissue of dairy goats and in regulating the occurrence of MFD are limited. Results:Eighteen Guanzhong dairy goats (day in milk?=?185?±?12 d) with similar parity, weight, and milk yield were selected and randomly assigned to one of three groups (n?=?6), which were fed an LRDS diet (Low RDS?=?20.52%), MRDS diet (Medium RDS?=?22.15%), or HRDS diet (High RDS?=?24.88%) for 5?weeks. Compared with that of the LRDS group, the milk fat contents in the MRDS and HRDS groups significantly decreased. The yields of short-, medium- and long-chain fatty acids decreased in the HRDS group. Furthermore, increased RDS significantly decreased ruminal B. fibrisolvens and Pseudobutyrivibrio abundances and increased the trans-10, cis-12 conjugated linoleic acid (CLA) and trans-10 C18:1 contents in the rumen fluid.A multiomics study revealed that the HRDS diet affected mammary lipid metabolism down-regulation of ACSS2, MVD, AGPS, SCD5, FADS2, CERCAM, SC5D, HSD17B7, HSD17B12, ATM, TP53RK, GDF1 and LOC102177400. Remarkably, the significant decrease of INSIG1, whose expression was depressed by trans-10, cis-12 CLA, could reduce the activity of SREBP and, consequently, downregulate the downstream gene expression of SREBF1. Conclusions:HRDS-induced goat MFD resulted from the downregulation of genes involved in lipogenesis, particularly, INSIG1. Specifically, even though the total starch content and the concentrate-to-fiber ratio were the same as those of the high-RDS diet, the low and medium RDS diets did not cause MFD in lactating goats.

Project description:Background:trans-10,cis-12 Conjugated linoleic acid (t10,c12-CLA) is a dietary supplement that promotes weight loss by increasing fat oxidation and energy expenditure. We previously reported that in the absence of t10,c12-CLA, mice forced to lose equivalent body weight by food restriction (FR) do not exhibit increases in fat oxidation or energy expenditure but have improved glucose metabolism, consistent with FR as a metabolically healthy weight-loss method. Objective:Because diet is a primary determinant of gut bacterial populations, we hypothesized that the disparate metabolic effects accompanying weight loss from t10,c12-CLA or FR could be related to altered intestinal microbiota. Methods:Ten-week-old male LDL receptor-deficient (Ldlr-/-) mice were fed a high-fat, high-sucrose diet (HFHS; 36% lard fat, 36.2% sucrose + 0.15% cholesterol) for 12 wk (baseline), then switched to the HFHS diet alone (obese control), HFHS + 1% c9,t11-CLA (obese fatty acid control), HFHS + 1% t10,c12-CLA (weight-loss-inducing fatty acid), or HFHS + FR (weight-loss control group with 75-85% ad libitum HFHS food intake) for a further 8 wk. Fecal microbial content, short-chain fatty acids (butyrate, acetate), tissue CLA concentrations, and intestinal nutrient transporter expression were quantified. Results:Mice fed t10,c12-CLA or assigned to FR lost 14.5% of baseline body weight. t10,c12-CLA-fed mice had elevated concentrations of fecal butyrate (2-fold) and plasma acetate (1.5-fold) compared with HFHS-fed controls. Fecal ? diversity decreased by 7.6-14% in all groups. Butyrivibrio and Roseburia, butyrate-producing microbes, were enriched over time by t10,c12-CLA. By comparing with each control group, we also identified bacterial genera significantly enriched in the t10,c12-CLA recipients, including Lactobacillus, Actinobacteria, and the newly identified Ileibacterium valens of the Allobaculum genus, whereas other taxa were enriched by FR, including Clostridiales and Bacteroides. Conclusion:Modalities resulting in equivalent weight loss but with divergent metabolic effects are associated with compositional differences in the mouse intestinal microbiota.

Project description:BackgroundDue to high neutral lipids accumulation in the cytoplasm, in vitro-produced embryos from Bos primigenius indicus and their crosses are more sensitive to chilling and cryopreservation than those from Bos primigenius taurus. The objective of the present study was to evaluate the effects of trans-10, cis-12 conjugated linoleic acid (CLA) on the development and cryotolerance of crossbred Bos primigenius taurus x Bos primigenius indicus embryos produced in vitro, and cultured in the presence of fetal calf serum. Bovine zygotes (n = 1,692) were randomly assigned to one of the following treatment groups: 1) Control, zygotes cultured in Charles Rosenkrans 2 amino acid (CR2aa) medium (n = 815) or 2) CLA, zygotes cultured in CR2aa medium supplemented with 100 μmol/L of trans-10, cis-12 CLA (n = 877). Embryo development (cleavage and blastocyst rates evaluated at days 3 and 8 of culture, respectively), lipid content at morula stage (day 5) and blastocyst cryotolerance (re-expansion and hatching rates, evaluated 24 and 72 h post-thawing, respectively) were compared between groups. Additionally, selected mRNA transcripts were measured by Real-Time PCR in blastocyst stage.ResultsThe CLA treatment had no effect on cleavage and blastocyst rates, or on mRNA levels for genes related to cellular stress and apoptosis. On the other hand, abundance of mRNA for the 1-acylglycerol-3-phosphate 0-acyltransferase-encoding gene (AGPAT), which is involved in triglycerides synthesis, and consequently neutral lipid content, were reduced by CLA treatment. A significant increase was observed in the re-expansion rate of embryos cultured with trans-10, cis-12 CLA when compared to control (56.3 vs. 34.4%, respectively, P = 0.002). However, this difference was not observed in the hatching rate (16.5 vs. 14.0%, respectively, P = 0.62).ConclusionsThe supplementation with trans-10, cis-12 CLA isomer in culture medium reduced the lipid content of in vitro produced bovine embryos by reducing the gene expression of 1-acylglycerol 3-phosphate 0-acyltransferase (AGPAT) enzyme. However, a possible improvement in embryo cryotolerance in response to CLA, as suggested by increased blastocyst re-expansion rate, was not confirmed by hatching rates.

Dataset Information

Trans-10, cis 12-Conjugated Linoleic Acid-Induced Milk Fat Depression Is Associated with Inhibition of PPAR? Signaling and Inflammation in Murine Mammary Tissue.

Publications

Trans-10, cis 12-Conjugated Linoleic Acid-Induced Milk Fat Depression Is Associated with Inhibition of PPARγ Signaling and Inflammation in Murine Mammary Tissue.

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