Obesity associated type 2 diabetes mellitus is the most common aggressive metabolic disorder [37]. However, the most key challenge in treating obesity associated type 2 diabetes mellitus is the presence of complexity [38]. Although previous investigations have reported various potential molecular markers linked with the advancement of obesity associated type 2 diabetes mellitus, the potential molecular mechanism underlying its pathogenesis has not been generally studied [39]. In the present investigation, a total of 820 DEGs were identified, containing 409 up regulated genes and 411 down regulated genes. SULT1C2 [40] and UBD (ubiquitin D) [41] were responsible for progression of kidney diseases, but these genes might be liable for advancement of obesity associated T2DM. HLA-DQA1 was associated with progression of T2DM [42]. SPX (spexin hormone) [43] and APOB (apolipoprotein B) [44] are a critical proteins plays an important role in obesity associated type 2 diabetes mellitus.
The GO and pathway enrichment analysis of DEG are closely related to obesity associated type 2 diabetes mellitus genes and advancement. KCNE5 [45], SHANK3 [46], CASQ2 [47], EDNRA (endothelin receptor type A) [48], EPHB4 [49], ALPK3 [50], WNT11 [51], IRAK2 [52], FBN1 [53], SFRP2 [54], CLCA2 [55], NEXN (nexilin F-actin binding protein) [56], PALLD (palladin, cytoskeletal associated protein) [57], DAB2 [58], NRP2 [59], THBS2 [60], CSF1R [61], KCNA2 [62], CACNA1C [63], F2R [64], UCHL1 [65], CCL18 [66], ITGB1BP2 [67] and FMOD (fibromodulin) [68] were reportedly involved in cardio vascular diseases, but these genes might be key for progression of obesity associated type 2 diabetes mellitus. Hu et al. [69], Liu et al. [70], Eltokhi et al. [71], Cai et al. [72], Pfeiffer et al. [73], Lin et al. [74], Royer-Zemmour et al. [75], Pastor et al. [76], Goodspeed et al. [77], Zhang et al. [78], Rogers et al. [79], Su et al. [80] and Foale et al. [81] reported that NRXN1, CRHR1, SHANK2, PSEN2, CKB (creatine kinase B), CD200R1, SRPX2, PTPRZ1, SLC6A1, GABRB2, KCNA1, ASAH1 and LINGO1 were linked with progression of neuropsychiatric disorders, but these genes might be involved in advancement of obesity associated type 2 diabetes mellitus. Reports indicate that SPHK2 [82], NPC1L1 [83], CNTFR (ciliaryneurotrophic factor receptor) [84], SLC2A4 [85], EDA (ectodysplasin A) [86], TGM2 [87], GCK (glucokinase) [88], FASN (fatty acid synthase) [89], FAP (fibroblast activation protein alpha) [90], PRNP (prion protein) [91], LYVE1 [92], SERPINE1 [93], TNF (tumor necrosis factor) [94], FASLG (Fas ligand) [95], HGF (hepatocyte growth factor) [96], FNDC5 [97], LBP (lipopolysaccharide binding protein) [98] and LOX (lysyl oxidase) [99] were found in obesity associated T2DM. Hirai et al [100], Vuori et al [101], Porta et al [102], Nomoto et al [103] and Blindbæk et al [104] demonstrates that VAMP2, CACNB2, SLC19A3, PFKFB3 and MFAP4 are essential for progression of type 1 diabetes, but these genes might be key for advancement of obesity associated type 2 diabetes mellitus. CACNA1A [105], ALK (ALK receptor tyrosine kinase) [106], SLC4A4 [107], STOX1 [108], COL3A1 [109], VNN1 [110], SLC4A7 [111], BDKRB2 [112], DRD1 [113] and LPAR1 [114] have reported significantly linked with hypertension, but these genes might be crucial for progression of obesity associated type 2 diabetes mellitus. KCNE2 [115], DLL1 [116], ACVR1C [117], RGS3 [118], MLXIPL (MLX interacting protein like) [119], PAG1 [120], SLC2A10 [121] and GRB14 [122] play important role in type 2 diabetes mellitus progression. A recent investigation has indicated that GPIHBP1 [123], FGFRL1 [124], DAPK2 [125], MAP3K5 [126], ANKK1 [127], GK (glycerol kinase) [128], SPHK1 [129], GNG3 [130], FSTL3 [131], SLIT2 [132], CCDC80 [133], RND3 [134], PTGER4 [135], RUNX1 [136], ADAM12 [137], OLR1 [138], THBS1 [139], CD28 [140], TRPV4 [141], ATRN (attractin) [142], MRC1 [143], SEMA3C [144], HTR2B [145], NOX4 [146], TACR1 [147], BAMBI [148], PDGFD (platelet derived growth factor D) [149], APLN (apelin) [150], MFAP5 [151] and LUM (lumican) [152] are associated with a development of obesity. A previous investigation found that DDR1 [153], TAB1 [154], NEK8 [155], SERPINE2 [156], FCGR2B [157], ANGPT2 [158], FN1 [159], SOCS5 [158], SMOC2 [160], CD2 [161] and SCN9A [162] expression were associated with a kidney diseases, but these genes might be responsible for advancement of obesity associated type 2 diabetes mellitus.
In addition, an investigation reported that hub genes serve an essential role in maintaining the entire PPI network and its modules are indispensable. Investigation has demonstrated that CEBPD (CCAAT enhancer binding protein delta) is one of the most important genes involved in obesity [163]. An investigation by Domingues-Montanari et al. [164] demonstrated that ESR2 is key for progression of cardio vascular disease, but this gene might be responsible for progression of obesity associated type 2 diabetes mellitus. TP73, PIK3R2, SLC9A3R1, KRT5, KRT14 and TFAP2C are novel biomarkers for pathogenesis of obesity associated type 2 diabetes mellitus.
The miRNA-target gene regulatory network and TF-target gene regulatory network highlighted in the current investigation provides new theoretical guidance for further exploring the mechanism of obesity associated type 2 diabetes mellitus and provides a new perspective for understanding the underlying biological processes of obesity associated type 2 diabetes mellitus, and miRNA and TF targeted therapy. Eberlé et al [165], Cheng et al [166], Cavallari et al [167], Qi et al [168] and Yan et al [169] indicated that SREBF1, MBD2, IRF4, CREB1 and RELA (Nuclear factor-kB) were responsible for advancement of obesity associated type 2 diabetes mellitus. Matsha et al [170] and Ding et al [171] demonstrated that hsa-mir-1299 and hsa-mir-4530 were liable for progression of type 2 diabetes mellitus. Hall et al [172] and Salazar-Mendiguchía et al [173] reported that FLNC (filamin C) and TRIM63were involved in progression of cardio vascular disease, but these genes might be essential for development of obesity associated type 2 diabetes mellitus. Xiao et al [174], Stratigopoulos et al [175] and Zhou et al [176] noted that ATF4, CUX1 and ZBTB7A were responsible for advancement of obesity. MAP1B, hsa-mir-4314, hsa-mir-5688, hsa-mir-583, hsa-mir-632, hsa-mir-3176, hsa-mir-4477a, hsa-mir-606, hsa-mir-1343-3p6, SIN3A, ZNF143 and SMARCE1 are the novel biomarkers for pathogenesis of obesity associated type 2 diabetes mellitus.
In conclusion, with the integrated bioinformatics analysis for expression profiling by high throughput sequencing in obesity associated type 2 diabetes mellitus, Ten hub genes associated with the pathogenesis and prognosis of obesity associated type 2 diabetes, including CEBPD, TP73, ESR2, TAB1, MAP3K5, FN1, UBD, RUNX1, PIK3R2 and TNF. These hub genes were all unregulated in obesity associated type 2 diabetes mellitus and first five (CEBPD, TP73, ESR2, TAB1 and MAP3K5) of them might be linked with targeted therapy. These hub genes may be regarded as new diagnostic and prognostic biomarkers for obesity associated type 2 diabetes mellitus. However, further in-depth investigation (in vivo and in vitro experiment) is necessary to elucidate the biological function of these genes in obesity associated type 2 diabetes mellitus.