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Transcriptional Changes in Mesenteric and Subcutaneous Adipose Tissue from Holstein Cows in Response to Plane of Dietary Energy

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Transcriptional Changes in Mesenteric and Subcutaneous Adipose Tissue from Holstein Cows in Response to Plane of Dietary Energy UC Davis UC Davis Previously Published Works Title Transcriptional changes in mesenteric and subcutaneous adipose tissue from Holstein cows in response to plane of dietary energy. Permalink https://escholarship.org/uc/item/5wp9h6fx Journal Journal of animal science and biotechnology, 8(1) ISSN 1674-9782 Authors Moisá, SJ Ji, P Drackley, JK et al. Publication Date 2017 DOI 10.1186/s40104-017-0215-z Peer reviewed eScholarship.org Powered by the California Digital Library University of California Moisá et al. Journal of Animal Science and Biotechnology (2017) 8:85 DOI 10.1186/s40104-017-0215-z RESEARCH Open Access Transcriptional changes in mesenteric and subcutaneous adipose tissue from Holstein cows in response to plane of dietary energy S. J. Moisá1,P.Ji2, J. K. Drackley2, S. L. Rodriguez-Zas2 and J. J. Loor2* 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. Keywords: Adipose tissue, Dairy cow, Dietary energy, Transcriptome * Correspondence: [email protected] 2Department of Animal Sciences, University of Illinois, Urbana 61801, USA Full list of author information is available at the end of the article © The Author(s). 2017 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. Moisá et al. Journal of Animal Science and Biotechnology (2017) 8:85 Page 2 of 15 Background body mass index (BMI) was correlated with quantitative Dairy cows can readily overconsume dietary energy dur- variations in the expression of genes. In that study, body ing the prepartum period [1]. Offering a high-energy mass was correlated with 1,304 transcripts, and among compared with a low-energy diet leads to increased in- the top 100 correlated genes a total of 30% encode ternal fat deposition [2]. Studies conducted by different macrophage-related proteins. For example, TNF-α, IL-6, research groups revealed that excess prepartal energy in- PAI-1, NO, factor VII, and MCP-1 were correlated with take induced higher prepartal plasma concentrations of adverse pathophysiological phenotypes associated with insulin, glucose and beta-hydroxy-butyric acid, in com- obesity [11]. iNOS and TNF-a were required for obesity- parison with controlled or restricted energy feeding. This induced insulin resistance in mice. Colony stimulating symptomatology was associated with greater peripheral factor 1 receptor (Csf1r) and CD68 antigen (Cd68) were lipolysis, with subsequent greater hepatic lipid accumu- positively correlated with BMI, and succinate dehy- lation at the onset of lactation that compromised animal drogenase complex iron sulfur subunit B (Sdhb), and health [3, 4]. A decrease in adipose tissue (AT) respon- ubiquinol–cytochrome c reductase (Uqcr), negatively siveness to insulin was proposed as the reason for nega- correlated with body mass. Clearly, gene transcription is tive effects on animal performance. a major control mechanism of AT lipogenesis during Adipose tissue is not simply a metabolic tissue that early lactation [12]. In the current study, we utilized dif- regulates whole body energy homeostasis, it also plays ferent bioinformatics tools (IPA, DAVID, and KEGG bio- an important endocrine function by secreting a number informatics software plus DIA) to identify the most- of proteins with signaling properties that are involved in enriched gene ontology (GO) functions and pathways in the regulation of metabolism (adiponectin, leptin), feed MAT and SAT of multiparous dairy cows in response to intake (leptin), and immune function and inflammation ad-libitum access for 8 wk of a high energy as compared (TNF-α, IL-1β) [5]. Despite the dominance of mature to a control diet. adipocytes, AT is also composed of immune cells (mac- rophages) and stromal-vascular cell fractions containing preadipocytes, endothelial cells, and mesenchymal stem Methods cells, which may vary in their response to external stim- Animals and tissue sample collection uli (such as nutrient supply) and immune activation [5]. All live-animal experimental procedures were approved Differences between visceral AT (VAT) and SAT in the by the Institutional Animal Care and Use Committee at proportion of cell types, capillary network, lipid storage the University of Illinois. This study used a subset of 10 capacity, endocrine activity, and responsiveness to lipo- cows (5/treatment) from a larger study [2, 7, 13] consist- lytic stimuli have been documented in humans and ro- ing of 18 non-pregnant and non-lactating Holstein cows dents [6]. In dairy cattle, VAT is more sensitive to (body weight = 656 ± 29 kg) from the University of Illi- dietary changes and it may have a significant effect on nois Dairy Research Unit. Cows averaged 3.0 parities whole body metabolic responses, particularly in the liver, (range 2 to 4). We used nonpregnant, nonlactating cows due to the direct portal drainage [7]. Some metabolic to replicate the effects of overfeeding in typical produc- disorders that occur frequently after parturition are asso- tion systems without the confounding hormonal changes ciated with macrophage infiltration into omental and that occur around parturition. Cows were blocked by subcutaneous fat, and coincide with a period of high initial BCS and previous experimental treatment and lipolytic activity [8]. In postpartum heifers, this could were randomly assigned within block to either a diet happen as early as 1 d after parturition [9]. It is cur- containing 1.35 Mcal/kg net energy for lactation (dry rently unknown if AT macrophage infiltration occurs matter basis; control group, CON) or 1.62 Mcal/kg (high in dairy cattle only during periods of negative energy energy group, HIGH) for 8 wk before slaughter and tis- balance [10]. sue collection. Nutrient composition of the experimental Large-scale mRNA expression techniques allow detec- diets can be found in a previous paper [2]. Samples of tion of changes in thousands of genes simultaneously, subcutaneous and mesenteric AT were harvested imme- which provides a holistic understanding when ad- diately post-slaughter and snap-frozen in liquid-N until equately compared to other omes. The combined RNA extraction. The different adipose depots located in utilization of bioinformatics analysis helps identify the the body vary in their impact on metabolic risk due to most enriched biological functions, pathways, and inherent differences in their metabolism (i.e., SAT is less physiological changes within the affected genes. As an metabolically active than MAT). Furthermore, dairy example, in a previous study in mice utilizing microarray cattle accumulate relatively more fat in internal adipose analysis
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