Transcriptomic profiling of adipose tissue inflammation, remodeling, and lipid metabolism in periparturient dairy cows (

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RESEARCH ARTICLE

Open Access

Transcriptomic profiling of adipose tissue inflammation, remodeling, and lipid metabolism in periparturient dairy cows (Bos taurus) David Salcedo-Tacuma1†, Jair Parales-Giron2†, Crystal Prom2, Miguel Chirivi3, Juliana Laguna2,3, Adam L. Lock2 and G. Andres Contreras3*

Abstract Background: Periparturient cows release fatty acid reserves from adipose tissue (AT) through lipolysis in response to the negative energy balance induced by physiological changes related to parturition and the onset of lactation. However, lipolysis causes inflammation and structural remodeling in AT that in excess predisposes cows to disease. The objective of this study was to determine the effects of the periparturient period on the transcriptomic profile of AT using NGS RNAseq. Results: Subcutaneous AT samples were collected from Holstein cows (n = 12) at 11 ± 3.6 d before calving date (PreP) and at 6 ± 1d (PP1) and 13 ± 1.4d (PP2) after parturition. Differential expression analyses showed 1946 and 1524 DEG at PP1 and PP2, respectively, compared to PreP. Functional Enrichment Analysis revealed functions grouped in categories such as lipid metabolism, molecular transport, energy production, inflammation, and free radical scavenging to be affected by parturition and the onset of lactation (FDR < 0.05). Inflammation related genes such as TLR4 and IL6 were categorized as upstream lipolysis triggers. In contrast, FASN, ELOVL6, ACLS1, and THRSP were identified as upstream inhibitors of lipid synthesis. Complement (C3), CXCL2, and HMOX1 were defined as links between inflammatory pathways and those involved in the generation of reactive oxygen species. Conclusions: Results offer a comprehensive characterization of gene expression dynamics in periparturient AT, identify upstream regulators of AT function, and demonstrate complex interactions between lipid mobilization, inflammation, extracellular matrix remodeling, and redox signaling in the adipose organ. Keywords: Periparturient period, Lipogenesis, Lipolysis, Adipose tissue inflammation

Background The transition from late pregnancy to early lactation (the periparturient period, PPE) represents a major metabolic challenge to mammals and is dependent on an extensive series of physiological adaptations that * Correspondence: [email protected] † David Salcedo-Tacuma and Jair Parales-Giron contributed equally to this work. 3 Department of Large Animal Clinical Sciences, College of Veterinary Medicine, Michigan State University, East Lansing, MI 48824, USA Full list of author information is available at the end of the article

include many, perhaps most, body tissues and involve all nutrient classes [1, 2]. The PPE is especially challenging in dairy cows as these animals have increased energy requirements driven by fetal growth and copious milk production. At the same time, cows have an inadequate appetite and feed intake to meet the energetic costs of maintenance plus pregnancy or lactation, resulting in a state of negative energy balance (NEB). This energetic deficit d