Hepatic transcriptome profile of sheep (Ovis aries) in response to overgrazing: novel genes and pathways revealed

Abstract

Background Overgrazing is a major factor that causes steppe degradation in Inner Mongolian, resulting in extensive ecosystem damage. Scarcity of grass means sheep are smaller and therefore mutton and cashmere production is greatly reduced, which has resulted in massive annual economic losses. Liver is the primary metabolic organ in mammals. It is also the key source of energy supply and detoxification of metabolites in animals, has a close relationship with animal growth. However, investigations on the responses of sheep induced by consequence of overgrazing, particularly those relating to liver-related molecular mechanisms and related metabolic pathways, remain elusive. Results The body weight daily gain of sheep, immune organ indices (liver and spleen), and serum parameters related to immune response, protein synthesis and energy supply (IgG, albumin, glucose and non-esterified fatty acid) were significantly lower in the overgrazing group. Other serum parameters including alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, total bilirubin, blood urea nitrogen and interleukin-6 were significantly higher in the overgrazing group. For the RNA-Seq results, we identified approximately 50 differentially expressed genes, of which half of were up-regulated and the other half were down-regulated (overgrazing group versus light grazing group). Bioinformatics analysis identified two enriched KEGG pathways including peroxisome proliferator-activated receptor (PPAR) signaling pathway (related to lipolysis) and ECM-receptor interaction (related to liver injury and apoptosis). Additionally, several of the down-regulated genes were related to detoxification and immune response. Conclusions Overall, based on the high-throughput RNA sequencing profile integrated with the results of serum biochemical analyses, consequences of lower forage availability and quality under overgrazing condition induced altered expression levels of genes participating in energy metabolism (particularly lipid metabolism) and detoxification and immune responses, causing lipolysis and impaired health status, which might be key reasons for the reduced growth performance of sheep. This investigation provides a novel foundation for the development of sheep hepatic gene interactive networks that are a response to the degraded forage availability under overgrazing condition. Electronic supplementary material The online version of this article (10.1186/s12863-019-0760-x) contains supplementary material, which is available to authorized users.

Liver transcriptome profiling and functional analysis of intrauterine growth restriction (IUGR) piglets reveals a genetic correction and sexual-dimorphic gene expression during postnatal development

“…High-throughput methods have been widely applied to understand both the physiological and pathological characteristics in the liver of various species [12][13][14]. In this study, we compared the liver transcriptomes between IUGR and normal neonatal piglets from Day 1 to Day 7, to the weaning day (Day 28) using whole-genome transcriptional sequencing, to gain insight into the dynamics of metabolism, growth, and development in IUGR piglets.…”

Transcriptomic and Metabolomic Analyses Reveal Inhibition of Hepatic Adipogenesis and Fat Catabolism in Yak for Adaptation to Forage Shortage During Cold Season

“…It has been demonstrated that GSTM3 and GSTK1 contributed to oxidative stress–mediated liver damage ( Uno et al, 2020 ). We observed that down-regulation of GSTM3 and GSTK1 expression in the liver of cold season grazing yaks, which may be due to shortage of forage and low temperature in the cold season, induced excessive physical activity and negative nutrient balance, thereby inducing oxidative stress and immune response ( Ren et al, 2019 ).…”

“…These complex lipids are stored in lipid droplets or secreted into the circulation as intestinally derived chylomicrons (CMs) and very low-density lipoprotein (VLDL) particles. The genes involved in lipid synthesis were down-regulated, whereas the pathways gluconeogenesis ( Yu et al, 2016 ), fatty acid oxidation ( Yu et al, 2016 ; Ren et al, 2019 ), and peroxisome proliferator-activated receptor A (PPAR-A) target genes (involved in lipolysis) ( Laporta et al, 2014 ) were up-regulated in ruminants under nutritional deprivation. However, the recent study suggests that lipid catabolism, fatty acid synthesis, glucose intake, and fatty acid oxidation in yaks were all inhibited by regulating the AMPK (adenosine 5′-monophosphate-activated protein kinase) signaling over cold seasons ( Xiong et al, 2020 ).…”

“…Studies have revealed that the regulation of hepatic gene expression plays a crucial role in hepatic metabolism by changing the capacity of enzymes in relevant metabolic pathways (Pamela A. Alexandre et al, 2015 ; Ren et al, 2019 ). Furthermore, results of the recent studies suggest that the genes involved in hepatic lipid synthesis (ACACA, FASN, LPL, SCD1, FADS1, and FADS2) were down-regulated over nutritional deficiency ( Kaufmann et al, 2012 ; Laporta et al, 2014 ; Vailati Riboni et al, 2015 ).…”

“…However, most of the current research is based on specific functional genes and enzymes, and the regulation of target pathways in the hepatic response of yak is less well understood under grazing conditions. The hepatic response in ruminants has been performed to reveal the pathways such as glycolysis or gluconeogenesis, fatty acid biosynthesis, extracellular matrix–receptor interaction, protein digestion and absorption, and cholesterol homeostasis, which play an essential role in nutritional metabolism ( Ren et al, 2018 ; Lu et al, 2019 ; Ren et al, 2019 ; Yu et al, 2019 ). Little information has been published concerning gene expression and target pathways in hepatic energy metabolism in yaks under natural grazing.…”