Developmentally Driven Changes in Adipogenesis in Different Fat Depots Are Related to Obesity

Abstract

Subcutaneous (sc) and visceral (vis) adipose tissue (AT) contribute to the variability in pathophysiological consequences of obesity and adverse fat distribution. To gain insights into the molecular mechanisms distinguishing vis and sc fat, we compared the transcriptome during differentiation of immortalized adipocytes from murine epididymal (epi) and inguinal (ing) AT. RNA was extracted on different days of adipogenesis (−2, 0, 2, 4, 6, 8) and analyzed using Clariom TM D mouse assays (Affymetrix) covering >214,900 transcripts in >66,100 genes. Transcript Time Course Analysis revealed 137 differentially expressed genes. The top genes with most divergent expression dynamics included developmental genes like Alx1, Lhx8, Irx1/2, Hoxc10, Hoxa5/10, and Tbx5/15. According to pathway analysis the majority of the genes were enriched in pathways related to AT development. Finally, in paired samples of human vis and sc AT (N = 63), several of these genes exhibited depot-specific variability in expression which correlated closely with body mass index and/or waist-to-hip ratio. In conclusion, intrinsically programmed differences in gene expression patterns during adipogenesis suggest that fat depot specific regulation of adipogenesis contributes to individual risk of obesity.

Multiomics reveal unique signatures of human epiploic adipose tissue related to systemic insulin resistance

“…Our methylation analysis results confirm findings previously published on homeobox and other genes involved in adipogenesis and browning of white AT. 36 37 Also, when comparing epiAT in the IR versus the IS state, we found a hypermethylated DMR close to CYP2E1 , the gene product of which is associated with oxidative stress and cellular damage in non-alcoholic fatty liver disease (NAFLD), obesity and T2D. 38 However, it should be noted that most of these previous findings are either from studies in mice, human peripheral blood leucocytes or other AT biopsies and not from epiAT, where data until now remain scarce.…”

Role of HOXC10 in Cancer

“…Earlier studies reported that HOXC10 was involved in regulating anterior/posterior pattern specification ( 22 – 24 ), limb regeneration ( 25 – 27 ), and lumbar motor neuron differentiation ( 28 – 31 ). HOXC10 is also associated with angiogenesis ( 32 ), fat metabolism ( 33 – 38 ), and sex regulation ( 39 ).…”

PTEN regulates adipose progenitor cell growth, differentiation, and replicative aging

“…( 26 ) comparing lipomas and subcutaneous adipose tissue of the same patient, and second, a study by Breitfeld et al. ( 27 ) comparing adipogenesis in murine inguinal and epididymal fat depots. We found an overlap of 36 genes ( Table S3 ), including some known regulators of adipogenesis such as FOXO1 ( 28 ) and genes such as RNF144B , which has no known function in adipose tissue yet.…”