Effects of Sex and Age on Inflammation-related Genes Expression in Omental Adipose Tissue of Holstein Cattle (Bos taurus) Based on Transcriptomics
CHAI Jin-Bao1,2, LIU Li1,*, WANG Fang1, YANG Shuo1, CAO Pei-Li1, ZHAO Xiao-Chuan1, XU Shan-Shan1, MENG Xiang-Ren1, BU Ye1, YUE Meng-Meng2, WU Rui2*, SUN Fang1
1 Key Laboratory of Combining Farming and Animal Husbandry of Ministry of Agriculture, Institute of Animal Husbandry, Heilongjiang Academy of Agricultural Sciences, Harbin 150086, China; 2 College of Animal Science and Veterinary Medicine, Heilongjiang Bayi Agricultural University, Daqing 163319, China
Abstract:Castration and long term fattening of bulls (Bos taurus) could promote visceral fat deposition, excessive fat deposition was easy to cause systemic chronic inflammation. However, there was very little known molecular mechanism of omental adipose tissue inflammation in cattle. The present study selected omental adipose tissue of cattle as research object, the aim of the present study was to evaluate the effects of sex and age on inflammation-related genes expression in omental adipose tissue of Holstein fattening cattle. Holstein bulls at 16 months of age (BF16 group, n=3) and Holstein steers at 16 and 26 months of age (SF16 and SF26 group, n=3) were selected. The growth performance and blood biochemical indexes were measured. After slaughtering, omental adipose tissue samples were collected for hematoxylin-eosin staining (HE) staining, transcriptome analysis was carried out for omental adipose tissue from three groups cattle by RNA- seq. Differentially expressed genes (DEGs) between groups was screened, GO function annotation, KEGG enrichment analysis, qPCR validation, candidate gene screening and protein-protein interaction network of differentially expressed genes were conducted. The results showed that a total 1 173 differentially expressed genes were identified, and enriched in 8 gene expression trend profiles. Functional analysis showed that the differentially genes were involved in multiple biological processes and signal pathways related to inflammation. Six differentially expressed genes were randomly selected for qPCR validation, and the results were consistent with transcriptome sequencing, which indicated that the sequencing results were reliable. Fifty non-redundant genes in 5 biological process items and 5 signaling pathways related to inflammation were screened. Cluster analysis showed that castration could upregulate the expression of anti-inflammatory and adipocyte differentiation genes (such as TNF alpha induced protein 3 (TNFAIP3), bone morphogenetic protein 2 (BMP2), etc) and downregulate the expression of proinflammatory genes (such as interleukin-1beta (IL1B)) in omental adipose tissue of SF16 group in comparison with BF16 group, long term fattening could upregulate the expression of genes related to aging and chronic inflammation (such as galectin 3 (LGALS3), C-C motif chemokine receptor 7 (CCR7), etc)) in omental adipose tissue of SF26 group in comparison with BF16 and SF16 groups. Protein-protein interaction network analysis showed that IL1B was the key central node. This research can serve as a theoretical basis for optimizing marbled beef production technology for Holstein steer.
柴金宝, 刘利, 王芳, 杨硕, 曹培丽, 赵晓川, 许珊珊, 孟详人, 卜也, 岳萌萌, 武瑞, 孙芳. 基于转录组学分析性别、月龄对荷斯坦牛网膜脂肪组织炎症相关基因表达的影响[J]. 农业生物技术学报, 2023, 31(5): 901-913.
CHAI Jin-Bao, LIU Li, WANG Fang, YANG Shuo, CAO Pei-Li, ZHAO Xiao-Chuan, XU Shan-Shan, MENG Xiang-Ren, BU Ye, YUE Meng-Meng, WU Rui, SUN Fang. Effects of Sex and Age on Inflammation-related Genes Expression in Omental Adipose Tissue of Holstein Cattle (Bos taurus) Based on Transcriptomics. 农业生物技术学报, 2023, 31(5): 901-913.
[1] 昝林森. 2007. 牛生产学(第二版)[M]. 中国农业出版社, 北京, pp. 296-297. (ZAN L S. 2007. Cattle Production (2nd Edition) [M]. China Agricultural Press, Beijing, China, pp. 296-297.) [2] Aratani Y. 2018. Myeloperoxidase: Its role for host defense, inflammation, and neutrophil function[J]. Archives of Biochemistry and Biophysics, 640: 47-52. [3] Beppu L Y, Mooli R G R, Qu X, et al. 2021. Tregs facilitate obesity and insulin resistance via a Blimp-1/IL-10 axis[J]. Journal of Clinical Investigation Insight, 6(3): e140644. [4] Bertola A, Ciucci T, Rousseau D, et al. 2012. Identification of adipose tissue dendritic cells correlated with obesity-associated insulin-resistance and inducing Th17 responses in mice and patients[J]. Diabetes, 61(9): 2238-2247. [5] Blüher M. 2016. Adipose tissue inflammation: A cause or consequence of obesity-related insulin resistance?[J]. Clinical Science (Lond). 130(18): 1603-1614. [6] Cho K W, Morris D L, DelProposto J L, et al. 2014. An MHC II-dependent activation loop between adipose tissue macrophages and CD4+ T cells controls obesity-induced inflammation[J]. Cell Reports, 9(2): 605-617. [7] Das S K, Sharma N K, Zhang B. 2015. Integrative network analysis reveals different pathophysiological mechanisms of insulin resistance among Caucasians and African Americans[J]. BMC Medical Genomics, 8(1): 1-21. [8] Di Nicola V. 2019. Omentum a powerful biological source in regenerative surgery[J]. Regenerative Therapy, 11: 182-191. [9] Duong B H, Onizawa M, Oses-Prieto J A, et al. 2015. A20 restricts ubiquitination of pro-interleukin-1β protein complexes and suppresses NLRP3 inflammasome activity[J]. Immunity, 42(1): 55-67. [10] Esser N, L'Homme L, Roover A D, et al. 2013. Obesity phenotype is related to NLRP3 inflammasome activity and immunological profile of visceral adipose tissue[J]. Diabetologia, 56(11): 2487-2497. [11] Fried S K, Bunkin D A, Greenberg A S. 1998. Omental and subcutaneous adipose tissues of obese subjects release interleukin-6: Depot difference and regulation by glucocorticoid[J]. The Journal of Clinical Endocrinology & Metabolism, 83(3): 847-850. [12] Grove K L, Fried S K, Greenberg A S, et al. 2010. A microarray analysis of sexual dimorphism of adipose tissues in high-fat-diet-induced obese mice[J]. International Journal of Obesity, 34(6): 989-1000. [13] Han M S, White A, Perry R J, et al. 2020. Regulation of adipose tissue inflammation by interleukin 6[J]. Proceedings of the National Academy of Sciences, 117(6): 2751-2760. [14] Harman-Boehm I, Blüher M, Redel H, et al. 2007. Macrophage infiltration into omental versus subcutaneous fat across different populations: Effect of regional adiposity and the comorbidities of obesity[J]. The Journal of Clinical Endocrinology & Metabolism, 92(6): 2240-2247. [15] Hellmann J, Sansbury B E, Holden C R, et al. 2016. CCR7 maintains nonresolving lymph node and adipose inflammation in obesity[J]. Diabetes, 65(8): 2268-2281. [16] Hoffstedt J, Arner E, Wahrenberg H, et al. 2010. Regional impact of adipose tissue morphology on the metabolic profile in morbid obesity[J]. Diabetologia, 53(12): 2496-2503. [17] Huang N, Hao D, Luo Y, et al. 2021. Th17 cells in periodontitis and its regulation by A20[J]. Frontiers in Immunology, 12: 742925. [18] Huang R L, Sun Y, Ho C K, et al. 2018. IL-6 potentiates BMP2-induced osteogenesis and adipogenesis via two different BMPR1A-mediated pathways[J]. Cell Death & Disease, 9(2): 1-15. [19] Huber J, Kiefer F W, Zeyda M, et al. 2008. CC chemokine and CC chemokine receptor profiles in visceral and subcutaneous adipose tissue are altered in human obesity[J]. The Journal of Clinical Endocrinology & Metabolism, 93(8): 3215-3221. [20] Kochumon S, Madhoun A A, Al-Rashed F, et al. 2020. Adipose tissue gene expression of CXCL10 and CXCL11 modulates inflammatory markers in obesity: Implications for metabolic inflammation and insulin resistance[J]. Therapeutic Advances in Endocrinology and Metabolism, 11: 571-579. [21] Kochumon S, Wilson A, Chandy B, et al. 2018. Palmitate activates CCL4 expression in human monocytic cells via TLR4/MyD88 dependent activation of NF- κB/MAPK/ PI3K signaling systems[J]. Cellular Physiology and Biochemistry, 46(3): 953-964. [22] Kusuyama J, Komorizono A, Bandow K, et al. 2016. CXCL3 positively regulates adipogenic differentiation[J]. Journal of Lipid Research, 57(10): 1806-1820. [23] Labrecque J, Michaud A, Gauthier M F, et al. 2018. Interleukin-1β and rostaglandin-synthesizing enzymes as modulators of human omental and subcutaneous adipose tissue function[J]. Prostaglandins Leukotrienes and Essential Fatty Acids, 141: 9-16. [24] Lee D, Kim D W, Yoon S, et al. 2021. CXCL5 secreted from macrophages during cold exposure mediates white adipose tissue browning[J]. Journal of Lipid Research, 62: 100117. [25] Liu T, Zhang L, Joo D, et al. 2017. NF-κB signaling in inflammation[J]. Signal Transduction and Targeted Therapy, 2(1): 17023. [26] Macotela Y, Boucher J, Tran T T, et al. 2009. Sex and depot differences in adipocyte insulin sensitivity and glucose metabolism[J]. Diabetes, 58(4): 803-812. [27] McLaughlin T, Liu L F, Lamendola C, et al. 2014. T-cell profile in adipose tissue is associated with insulin resistance and systemic inflammation in humans[J]. Arteriosclerosis, Thrombosis, and Vascular Biology, 34(12): 2637-2643. [28] Mitterberger M C, Lechner S, Mattesich M, et al. 2012. DLK1 (PREF1) is a negative regulator of adipogenesis in CD105+/CD90+/CD34+/CD31-/FABP4- adipose-derived stromal cells from subcutaneous abdominal fat pats of adult women[J]. Stem Cell Research, 9(1): 35-48. [29] Nguyen H P, Lin F, Yi D, et al. 2021. Aging-dependent regulatory cells emerge in subcutaneous fat to inhibit adipogenesis[J]. Developmental Cell, 56(10): 1437-1451. [30] Nishimura S, Manabe I, Nagasaki M, et al. 2009. CD8+ effector T cells contribute to macrophage recruitment and adipose tissue inflammation in obesity[J]. Nature Medicine, 15(8): 914-920. [31] Norling L V, Perretti M, Cooper D. 2009. Endogenous galectins and the control of the host inflammatory response[J]. The Journal of Endocrinology, 201(2): 169-184. [32] Rhodes D H, Pini M, Castellanos K J, et al. 2013. Adipose tissue specific modulation of galectin expression in lean and obese mice: Evidence for regulatory function[J]. Obesity, 21(2): 310-319. [33] Röszer T. 2021. Adipose tissue immunometabolism and apoptotic cell clearance[J]. Cells, 10(9): 2288. [34] Schreiber I, Dörpholz G, Ott C E, et al. 2017. BMPs as new insulin sensitizers: Enhanced glucose uptake in mature 3T3-L1 adipocytes via PPARγ and GLUT4 upregulation[J]. Scientific Reports, 7(1): 17192. [35] Varghese M, Song J, Singer K. 2021. Age and sex: Impact on adipose tissue metabolism and inflammation[J]. Mechanisms of Ageing and Development, 199: 111563. [36] Vasanthakumar A, Chisanga D, Blume J, et al. 2020. Sex-specific adipose tissue imprinting of regulatory T cells[J]. Nature, 579(7800): 581-585. [37] Velotti F, Barchetta I, Cimini F A, et al. 2020. Granzyme B in inflammatory diseases: Apoptosis, inflammation, extracellular matrix remodeling, epithelial-to-mesenchymal transition and fibrosis[J]. Frontiers in Immunology, 11: 587581. [38] Wei F, Zhou Y, Wang J, et al. 2018. The immunomodulatory role of BMP-2 on macrophages to accelerate osteogenesis[J]. Tissue Engineering Part A, 24(7-8): 584-594. [39] Yin Z, Deng T, Peterson L E, et al. 2014. Transcriptome analysis of human adipocytes implicates the NOD-like receptor pathway in obesity-induced adipose inflammation[J]. Molecular & Cellular Endocrinology, 394(1-2): 80-87. [40] Zhao X, Xie H, Zhao M, et al. 2019. Fc receptor-like 1 intrinsically recruits c-Abl to enhance B cell activation and function[J]. Science Advances, 5(7): eaaw0315.