Critical Genes in White Adipose Tissue Based on Gene Expression Profile Following Exercise

Abstract

Exercise is recognized as an effective method to prevent obesity and alleviate metabolic diseases. Browning of white adipose has the advantage of decreasing insulin resistance. We aim to identify critical differentially expressed genes (DEGs) in white adipose tissue after exercise. We downloaded the gene dataset GSE68161 of C57BL/6 mice from the Gene Expression Omnibus (GEO) database. Then, we analyzed the effect of exercise on up-regulated and down-regulated DEGs by GEO2R and performed protein-protein interaction network analyses. We then identified hub-genes in white adipose tissue and crosstalk genes of a single pathway by the STRING database and Cytoscape. In this study, 72 DEGs were screened out, and they mainly function in glycerol-3-phosphate dehydrogenase activity and in the primary biological process of fatty acid oxidation regulation. The top 5 hub-genes screened out were SLC27A1, COX7A1, PPARGC1A, FABP3, and UCP1. The 3 crosstalk genes found were SLC27A1, SLC27A2, and PPARA. These 3 genes might function as a bridge of the PPAR signaling pathway, adipocytokine signaling pathway and the insulin resistance pathway. SLC27A1 is critical gene for the interactions of signaling pathways in subcutaneous white adipose tissue. Therefore, further relationships between the browning of white adipose and insulin resistance need to be studied.

Key words

exercise - differentially expressed gene - enrichment analysis - network

• References

• 1 Aldiss P, Betts J, Sale C, Pope M, Budge H, Symonds ME. Exercise-induced ‘browning’ of adipose tissues. Metabolism 2018; 81: 63-70
• 2 Barbeau P, Johnson MH, Howe CA, Allison J, Davis CL, Gutin B, Lemmon CR. Ten months of exercise improves general and visceral adiposity, bone, and fitness in black girls. Obesity 2007; 15: 2077-2085
• 3 Boström P, Wu J, Jedrychowski MP, Korde A, Ye L, Lo JC, Rasbach Ka, Boström EA, Choi JH, Long JZ, Zingaretti MC, Vind BF, Tu H, Cinti S, Gygi SP, Spiegelman BM. A PGC1a dependent myokine that derives browning of white fat and thermogenesis. Nature 2012; 481: 463-468
• 4 Carreras A, Zhang SX, Peris E, Qiao Z, Wang Y, Almendros I, Gozal D. Effect of resveratrol on visceral white adipose tissue inflammation and insulin sensitivity in a mouse model of sleep apnea. Int J Obes 2015; 39: 418-423
• 5 Donnelly JE, Honas JJ, Smith BK, Mayo MS, Gibson CA, Sullivan DK, Lee J, Herrmann SD, Lambourne K, Washburn RA. Aerobic exercise alone results in clinically significant weight loss for men and women: Midwest exercise trial 2. Obesity 2013; 21: E219-E228
• 6 Fisichella M, Stewart A, Cuzzocrea A, Denecke K. Detecting health events on the social web to enable epidemic intelligence. In: Grossi R, Sebastiani F, Silvestri F (eds.) String Processing and Information Retrieval. SPIRE 2011. Lecture Notes in Computer Science, vol 7024. Springer, Berlin, Heidelberg. 2011; 87-103
• 7 Harriss DJ, Macsween A, Atkinson G. Standards for ethics in sport and exercise science research: 2018 update. Int J Sports Med 2017; 38: 1126-1131
• 8 Holland AM, Hyatt HW, Smuder AJ, Sollanek KJ, Morton AB, Roberts MD, Kavazis AN. Influence of endurance exercise training on antioxidant enzymes, tight junction proteins, and inflammatory markers in the rat ileum. BMC Res Notes 2015; 8: 514
• 9 Hui X, Gu P, Zhang J, Nie T, Pan Y, Wu D, Feng T, Zhong C, Wang Y, Lam KSL, Xu A. Adiponectin enhances cold-induced browning of subcutaneous adipose tissue via promoting m2 macrophage proliferation. Cell Metab 2015; 22: 279-290
• 10 Hunter GR, Brock DW, Byrne NM, Chandler-Laney PC, Del Corral P, Gower BA. Exercise training prevents regain of visceral fat for 1 year following weight loss. Obesity 2010; 18: 690-695
• 11 Jeong H, Mason SP, Barabási AL, Oltvai ZN. Lethality and centrality in protein networks. Nature 2001; 411: 41-42
• 12 Jorge MLMP, De Oliveira VN, Resende NM, Paraiso LF, Calixto A, Diniz ALD, Resende ES, Ropelle ER, Carvalheira JB, Espindola FS, Jorge PT, Geloneze B. The effects of aerobic, resistance, and combined exercise on metabolic control, inflammatory markers, adipocytokines, and muscle insulin signaling in patients with type 2 diabetes mellitus. Metabolism 2011; 60: 1244-1252
• 13 Massaro M, Scoditti E, Pellegrino M, Carluccio MA, Calabriso N, Wabitsch M, Storelli C, Wright M, De Caterina R. Therapeutic potential of the dual peroxisome proliferator activated receptor (PPAR)α/γ agonist aleglitazar in attenuating TNF-α-mediated inflammation and insulin resistance in human adipocytes. Pharmacol Res 2016; 107: 125-136
• 14 Osler ME, Fritz T, Caidahl K, Krook A, Zierath JR, Wallberg-Henriksson H. Changes in gene expression in responders and nonresponders to a low-intensity walking intervention. Diabetes Care 2015; 38: 1154-1160
• 15 Park S, Kim DS, Kang S. Vitamin D deficiency impairs glucose-stimulated insulin secretion and increases insulin resistance by reducing PPAR-γ expression in nonobese Type 2 diabetic rats. J Nutr Biochem 2016; 27: 257-265
• 16 Pitre S, Alamgir M, Green JR, Dumontier M, Dehne F, Golshani A. Computational methods for predicting protein-protein interactions. In: Protein–Protein Interaction. 2008; 247-267
• 17 Reichkendler MH, Rosenkilde M, Auerbach PL, Agerschou J, Nielsen MB, Kjaer A, Hoejgaard L, Sjödin A, Ploug T, Stallknecht B. Only minor additional metabolic health benefits of high as opposed to moderate dose physical exercise in young, moderately overweight men. Obesity 2014; 22: 1220-1232
• 18 Richard JE, López-Ferreras L, Chanclón B, Eerola K, Micallef P, Skibicka KP, Wernstedt Asterholm I. CNS β3-adrenergic receptor activation regulates feeding behavior, white fat browning, and body weight. Am J Physiol Endocrinol Metab 2017; 313: E344-E358
• 19 Ringholm S, Grunnet Knudsen J, Leick L, Lundgaard A, Munk Nielsen M, Pilegaard H. PGC-1α is required for exercise- and exercise training-induced ucp1 up-regulation in mouse white adipose tissue. PLoS One 2013; 8: 1-6
• 20 Stanford KI, Middelbeek RJW, Goodyear LJ. Exercise effects on white adipose tissue: Beiging and metabolic adaptations. Diabetes 2015; 64: 2361-2368
• 21 Stanford KI, Middelbeek RJW, Townsend KL, Lee M-Y, Takahashi H, So K, Hitchcox KM, Markan KR, Hellbach K, Hirshman MF, Tseng Y-H, Goodyear LJ. A Novel role for subcutaneous adipose tissue in exercise-induced improvements in glucose homeostasis. Diabetes 2015; 64: 2002-2014
• 22 Sun Y, Cui D, Zhang Z, Zhang T, Shi J, Jin H, Ge Z, Ji L, Ding S. Attenuated oxidative stress following acute exhaustive swimming exercise was accompanied with modified gene expression profiles of apoptosis in the skeletal muscle of mice. Oxid Med Cell Longev 2016; 2016: 8381242
• 23 Tran TT, Kahn CR. Transplantation of adipose tissue and stem cells: Role in metabolism and disease. Nat Rev Endocrinol 2010; 6: 195-213
• 24 Wiczer BM, Bernlohr DA. A novel role for fatty acid transport protein 1 in the regulation of tricarboxylic acid cycle and mitochondrial function in 3T3-L1 adipocytes. J Lipid Res 2009; 50: 2502-2513
• 25 Winer DA, Luck H, Tsai S, Winer S. The intestinal immune system in obesity and insulin resistance. Cell Metab 2016; 23: 413-426
• 26 Wu J, Boström P, Sparks LM, Ye L, Choi JH, Giang AH, Khandekar M, Virtanen KA, Nuutila P, Schaart G, Huang K, Tu H, Van Marken Lichtenbelt WD, Hoeks J, Enerbäck S, Schrauwen P, Spiegelman BM. Beige adipocytes are a distinct type of thermogenic fat cell in mouse and human. Cell 2012; 150: 366-376