Dataset Information

Transcriptional changes in mesenteric and subcutaneous adipose tissue from Holstein cows in response to plane of dietary energy.

ABSTRACT: Background:Dairy cows can readily overconsume dietary energy during most of the prepartum period, often leading to higher prepartal concentrations of insulin and glucose and excessive body fat deposition. The end result of these physiologic changes is greater adipose tissue lipolysis post-partum coupled with excessive hepatic lipid accumulation and compromised health. Although transcriptional regulation of the adipose response to energy availability is well established in non-ruminants, such regulation in cow adipose tissue depots remains poorly characterized. Results:Effects of ad-libitum access to high [HIGH; 1.62 Mcal/kg of dry matter (DM)] or adequate (CON; 1.35 Mcal/kg of DM) dietary energy for 8 wk on mesenteric (MAT) and subcutaneous (SAT) adipose tissue transcript profiles were assessed in non-pregnant non-lactating Holstein dairy cows using a 13,000-sequence annotated bovine oligonucleotide microarray. Statistical analysis revealed 409 and 310 differentially expressed genes (DEG) due to tissue and diet. Bioinformatics analysis was conducted using the Dynamic Impact Approach (DIA) with the KEGG pathway database. Compared with SAT, MAT had more active biological processes related to adipose tissue accumulation (adiponectin secretion) and signs of pro-inflammatory processes due to adipose tissue expansion and macrophage infiltration (generation of ceramides). Feeding the HIGH diet led to changes in mRNA expression of genes associated with cell hypertrophy (regucalcin), activation of adipogenesis (phospholipid phosphatase 1), insulin signaling activation (neuraminidase 1) and angiogenesis (semaphorin 4G, plexin B1). Further, inflammation due to HIGH was underscored by mRNA expression changes associated with oxidative stress response (coenzyme Q3, methyltransferase), ceramide synthesis (N-acylsphingosine amidohydrolase 1), and insulin signaling (interferon regulatory factor 1, phosphoinositide-3-kinase regulatory subunit 1, retinoic acid receptor alpha). Activation of ribosome in cows fed HIGH indicated the existence of greater adipocyte growth rate (M-phase phosphoprotein 10, NMD3 ribosome export adaptor). Conclusions:The data indicate that long-term ad-libitum access to a higher-energy diet led to transcriptional changes in adipose tissue that stimulated hypertrophy and the activity of pathways associated with a slight but chronic inflammatory response. Further studies would be helpful in determining the extent to which mRNA results also occur at the protein level.

SUBMITTER: Moisa SJ

PROVIDER: S-EPMC5713657 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Transcriptional changes in mesenteric and subcutaneous adipose tissue from Holstein cows in response to plane of dietary energy.

Moisá S J SJ Ji P P Drackley J K JK Rodriguez-Zas S L SL Loor J J JJ

Journal of animal science and biotechnology 20171204

<h4>Background</h4>Dairy cows can readily overconsume dietary energy during most of the prepartum period, often leading to higher prepartal concentrations of insulin and glucose and excessive body fat deposition. The end result of these physiologic changes is greater adipose tissue lipolysis post-partum coupled with excessive hepatic lipid accumulation and compromised health. Although transcriptional regulation of the adipose response to energy availability is well established in non-ruminants, ...[more]

PMID: 29214018

Similar Datasets

Project description:BackgroundThe aim of the study was to investigate the effect of energy overfeeding during the dry period on adipose tissue transcriptome profiles during the periparturient period in dairy cows.MethodsFourteen primiparous Holstein cows from a larger cohort receiving a higher-energy diet (1.62 Mcal of net energy for lactation/kg of dry matter; 15% crude protein) for ad libitum intake to supply 150% (OVR) or 100% (CTR) of energy requirements from dry off until parturition were used. After calving, all cows received the same lactation diet. Subcutaneous adipose tissue (SAT) biopsies were collected at - 14, 1, and 14 d from parturition (d) and used for transcriptome profiling using a bovine oligonucleotide microarray. Data mining of differentially expressed genes (DEG) between treatments and due to sampling time was performed using the Dynamic Impact Approach (DIA) and Ingenuity Pathway Analysis (IPA).ResultsThere was a strong effect of over-feeding energy on DEG with 2434 (False discovery rate-corrected P < 0.05) between OVR and CTR at - 14 d, and only 340 and 538 at 1 and 14 d. The most-impacted and activated pathways in the Kyoto Encyclopedia of Genes and Genomes (KEGG) database that were highlighted by DIA analysis at - 14 d in OVR vs. CTR included 9 associated with carbohydrate metabolism, with 'Pyruvate metabolism', 'Glycolysis/gluconeogenesis', and 'Pentose phosphate pathway' among the most-activated. Not surprisingly, OVR led to marked activation of lipid metabolism (e.g. 'Fatty acid biosynthesis' and 'Glycerolipid metabolism'). Unexpected metabolic pathways that were activated at - 14 d in OVR included several related to metabolism of amino acids (e.g. branched chain) and of cofactors and vitamins (thiamin). Among endocrine and immune system pathways, at - 14 d OVR led to marked activation of 'PPAR signalling' and 'Antigen processing and presentation'. Among key pathways affected over time in OVR, a number were related to translation (e.g. mTOR signaling), endocrine/immune signaling (CXCR4 and IGF1), and lipid metabolism (oxidative phosphorylation) with greater activation in OVR vs. CTR specifically at - 14 d. Although statistical differences for several pathways in OVR vs. CTR nearly disappeared at 1 and 14 vs. - 14 d, despite the well-known catabolic state of adipose depots after calving, the bioinformatics analyses suggested important roles for a number of signaling mechanisms at - 14 vs. 14 than 1 vs. -14 d. This was particularly evident in cows fed to meet predicted energy requirements during the dry period (CTR).ConclusionsData underscored a strong activation by overfeeding energy of anabolic processes in the SAT exclusively prepartum. The study confirmed that higher-energy diets prepartum drive a transcriptional cascade of events orchestrated in part by the activation of PPARγ that regulate preadipocyte differentiation and lipid storage in SAT. Novel aspects of SAT biology to energy overfeeding or change in physiologic state also were uncovered, including the role of amino acid metabolism, mTOR signaling, and the immune system.

Project description:Ketosis is a major metabolic disorder of high-yielding dairy cows during the transition period. Although metabolic adaptations of the adipose tissue are critical for a successful transition, beyond lipolysis, alterations within adipose tissue during ketosis are not well known. The objective of this study was to investigate the adipose tissue proteome of healthy or ketotic postpartum cows to gain insights into biological adaptations that may contribute to disease outcomes. Adipose tissue biopsy was collected on 5 healthy and 5 ketotic cows at 17 (±4) d postpartum and ketosis was defined according to the clinical symptoms and serum ?-hydroxybutyrate concentration. Morphology micrographs stained by hematoxylin-eosin showed that adipocytes were smaller in ketotic cows than in healthy cows. The isobaric tag for relative and absolute quantification was applied to quantitatively identify differentially expressed proteins (DEP) in the adipose tissue. We identified a total of 924 proteins, 81 of which were differentially expressed between ketotic and healthy cows (P < 0.05 and fold changes >1.5 or <0.67). These DEP included enzymes and proteins associated with various carbohydrate, lipid, and amino acid metabolism processes. The top pathways differing between ketosis and control cows were glycolysis/gluconeogenesis, glucagon signaling pathway, cysteine and methionine metabolism, biosynthesis of amino acids, and the cGMP-PKG signaling pathway. The identified DEP were further validated by western blot and co-immunoprecipitation assay. Key enzymes associated with carbohydrate metabolism such as pyruvate kinase 2, pyruvate dehydrogenase E1 component subunit ?), lactate dehydrogenase A , phosphoglucomutase 1, and 6-phosphofructokinase 1 were upregulated in ketotic cows. The expression and phosphorylation state of critical regulators of lipolysis such as perilipin-1 and hormone-sensitive lipase were also upregulated in ketotic cows. Furthermore, key proteins involved in maintaining innate immune response such as lipopolysaccharide binding protein and regakine-1 were downregulated in ketotic cows. Overall, data indicate that ketotic cows during the transition period have altered carbohydrate, lipid metabolism, and impaired immune function in the adipose tissue. This proteomics analysis in adipose tissue of ketotic cows identified several pathways and proteins that are components of the adaptation to ketosis.

Project description:The severity of negative energy balance (NEB) in high-producing dairy cows has a high incidence among health diseases. The cow's energy status during early lactation critically affects metabolic and reproductive parameters. The first objective of this study was to investigate by RNA-seq analysis and RT-qPCR the gene expression profile in white adipose tissue and by gene ontology and upstream regulation tools the relationships with energy metabolism and reproduction in two groups of primiparous dairy cows with extreme NEB statuses (NEB < -9 Mcal/day vs. NEB > -9 Mcal/day) around parturition. The second objective was to determine the potential involvement of a new adipokine identified as a candidate for the regulation of ovarian function in our RNA-seq analysis by using bovine primary granulosa culture, thymidine incorporation to determine cell proliferation and ELISA assays to measure progesterone secretion. The RNA-seq analysis revealed that 514 genes were over-expressed and 695 were under-expressed in the adipose tissue of cows with severe NEB (SNEB) and cows with moderate NEB (MNEB) during the -4 and 16 wkpp period. In addition, 491 genes were over-expressed and 705 genes were under-expressed in the adipose tissue of SNEB cows compared to MNEB cows. Among these differently expressed genes (DEGs), 298 were related to metabolic functions and 264 to reproductive traits. A set of 19 DEGs were validated by RT-qPCR, including CCL21 (C-C motif chemokine ligand 21). Moreover, CCL21, a gene known to be secreted by adipose tissue, was chosen for further analysis in plasma and ovaries. The use of next-generation sequencing technologies allowed us to characterise the transcriptome of white adipose tissue from primiparous cows with different levels of NEB during lactation. This study highlighted the alteration of the expression of genes related to lipid metabolism, including CCL21, which is released in the bloodstream and associated with the in vitro regulation of ovarian functions.

Project description:The effects of dietary energy level and 2,4-thiazolidinedione (TZD) injection on feed intake, body fatness, blood biomarkers and TZD concentrations, genes related to insulin sensitivity in adipose tissue (AT) and skeletal muscle, and peroxisome proliferator-activated receptor gamma (PPARG) protein in subcutaneous AT (SAT) were evaluated in Holstein cows. Fourteen nonpregnant nonlactating cows were fed a control low-energy (CON, 1.30 Mcal/kg) diet to meet 100% of estimated nutrient requirements for 3 weeks, after which half of the cows were assigned to a higher-energy diet (OVE, 1.60 Mcal/kg) and half of the cows continued on CON for 6 weeks. All cows received an intravenous injection of TZD starting 2 weeks after initiation of dietary treatments and for an additional 2 weeks, which served as the washout period. Cows fed OVE had greater energy intake and body mass than CON, and TZD had no effect during the administration period. The OVE cows had greater TZD clearance rate than CON cows. The lower concentration of nonesterified fatty acids (NEFA) and greater concentration of insulin in blood of OVE cows before TZD injection indicated positive energy balance and higher insulin sensitivity. Administration of TZD increased blood concentrations of glucose, insulin, and beta-hydroxybutyrate (BHBA) at 2 to 4 weeks after diet initiation, while the concentration of NEFA and adiponectin (ADIPOQ) remained unchanged during TZD. The TZD upregulated the mRNA expression of PPARG and its targets FASN and SREBF1 in SAT, but also SUMO1 and UBC9 which encode sumoylation proteins known to down-regulate PPARG expression and curtail adipogenesis. Therefore, a post-translational response to control PPARG gene expression in SAT could be a counteregulatory mechanism to restrain adipogenesis. The OVE cows had greater expression of the insulin sensitivity-related genes IRS1, SLC2A4, INSR, SCD, INSIG1, DGAT2, and ADIPOQ in SAT. In skeletal muscle, where PPARA and its targets orchestrate carbohydrate metabolism and fatty acid oxidation, the OVE cows had greater glyceroneogenesis (higher mRNA expression of PC and PCK1), whereas CON cows had greater glucose transport (SLC2A4). Administration of TZD increased triacylglycerol concentration and altered expression of carbohydrate- and fatty acid oxidation-related genes in skeletal muscle. Results indicate that overfeeding did not affect insulin sensitivity in nonpregnant, nonlactating dairy cows. The bovine PPARG receptor appears TZD-responsive, with its activation potentially leading to greater adipogenesis and lipogenesis in SAT, while differentially regulating glucose homeostasis and fatty acid oxidation in skeletal muscle. Targeting PPARG via dietary nutraceuticals while avoiding excessive fat deposition might improve insulin sensitivity in dairy cows during times such as the peripartal period when the onset of lactation naturally decreases systemic insulin release and sensitivity in tissues such as AT.

Dataset Information

Transcriptional changes in mesenteric and subcutaneous adipose tissue from Holstein cows in response to plane of dietary energy.

Publications

Transcriptional changes in mesenteric and subcutaneous adipose tissue from Holstein cows in response to plane of dietary energy.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets