Abstract

   Obesity remains as a global epidemic characterized by progressive
   metabolic dysregulation in glucose homeostasis. Along with a genetic
   association in the development of T2D, epigenetic regulation has been
   suggested as a significant contributor in altered gene expression.
   Recent studies have described DNA methylation changes in
   insulin-sensitive tissues involved in T2D pathogenesis, however
   epigenetic dynamics on early stages to metabolic alterations is still
   unclear.

   We investigated potential DNA methylation signatures in 34 asymptomatic
   individuals from the GEMM family study. We compared differentially
   methylated CpG sites (DMC: B value>0 and delta Beta >|10%|; Infinium
   EPIC array) from subcutaneous adipose tissue (SCAT) in different groups
   of individuals according to BMI (kg/m^2) and HbA1c (%) levels as
   follow: Group A Control (C): n=9, 22.0±1.9 kg/m^2, 4.8±0.3%; Group B
   Overweight (OW) with normal HbA1c: n=6, 27.8±1.6 kg/m^2, 5±0.2%; Group
   C Obese (OB) with normal HbA1c: n=6, 34.6±4.2 kg/m^2, 5.2±0.2%; Group D
   Prediabetes (PD): n=7, 31.1±5.7 kg/m^2, 5.9±0.2% and Group E T2D: n=6,
   30.6±7.3 kg/m^2, 7.2±0.9%.

   We found 43 overlapping genes with shared pathways in all groups,
   mainly those related to metabolism and adipogenesis. We also documented
   particular altered methylated genes, in each group (OW: 386, OB:1005,
   PD:76 and T2D:189). Pathway enrichment analysis in OB and T2D was
   mainly related to glucose metabolism, while in OW and PD was NOTCH
   signaling. All groups displayed a consistent hypermethylation in RARA,
   ESR1 and NCOR2, well known genes involved in lipid metabolism.
   Additionally, we describe for the first time, a progression toward
   hypomethylation in ARHGAP15 and MTAP, related with an impaired
   metabolic status. Otherwise, analysis of overlapping CpG sites revealed
   a consistently hypermethylated state in OW (86.42%), OB (86.48%) and PD
   (51.72%), in contrast with the hypomethylation state (56.3%) observed
   in the T2D group, previously observed elsewhere (1).

   In conclusion, comparison of methylation in SCAT obtained from OW, OB,
   PD and T2D individuals, display potential pathways and DMC signatures
   specific in each group. Common novel overlapping genes in global DNA
   methylation profiles of SCAT, were also observed.

   Reference: (1) Barajas-Olmos et al., BMC Med Genet. 2018 Feb
   21;19(1):1-8.

   Nothing to Disclose: FE, FB, AM, EH, GEMM, ER, RB, LO.
     __________________________________________________________________

   Articles from Journal of the Endocrine Society are provided here
   courtesy of The Endocrine Society
   (BUTTON) Close

ACTIONS

     * [37]View on publisher site
     * [38]PDF (69.8 KB)
     * (BUTTON) Cite
     * (BUTTON) Collections
     * (BUTTON) Permalink

PERMALINK
       https://pmc.ncbi.nlm (BUTTON) Copy

RESOURCES

(BUTTON) Similar articles

(BUTTON) Cited by other articles

(BUTTON) Links to NCBI Databases

Cite

   (BUTTON)
     * (BUTTON) Copy
     * [39]Download .nbib .nbib
     * Format: [NLM]

Add to Collections

   ( ) Create a new collection
   (*) Add to an existing collection

   Name your collection * ____________________
   Choose a collection
   Unable to load your collection due to an error
   [40]Please try again

   (BUTTON) Add (BUTTON) Cancel

   Follow NCBI
   [41]NCBI on X (formerly known as Twitter) [42]NCBI on Facebook [43]NCBI
   on LinkedIn [44]NCBI on GitHub [45]NCBI RSS feed

   Connect with NLM
   [46]NLM on X (formerly known as Twitter) [47]NLM on Facebook [48]NLM on
   YouTube


    [49]National Library of Medicine
    8600 Rockville Pike
    Bethesda, MD 20894

     * [50]Web Policies
     * [51]FOIA
     * [52]HHS Vulnerability Disclosure

     * [53]Help
     * [54]Accessibility
     * [55]Careers

     * [56]NLM
     * [57]NIH
     * [58]HHS
     * [59]USA.gov

   (BUTTON) Back to Top

References