The common pathophysiologic threads between Asian Indian diabetic's 'Thin Fat Phenotype' and partial lipodystrophy: the peripheral adipose tissue transcriptomic evidences

Adipocyte. 2020 Jan 1;9(1):253-263. doi: 10.1080/21623945.2020.1776082.

Abstract

T2D is a complex disease with poorly understood mechanisms. In Asian Indians, it is associated with "thin fat" phenotype which resembles with partial lipodystrophy. We hypothesized that disturbed expression of lipodystrophy genes might play a role in T2D pathogenesis. Therefore, we attempted to establish a link between these two diseases by studying the overlap between the network of lipodystrophy genes and the differentially expressed genes (DEGs) in the peripheral subcutaneous adipose tissue of Asian Indians diabetics. We found that 16, out of 138 lipodystrophy genes were differentially regulated in diabetics and around 18% overlap between their network and the DEGs; the expression level of lipodystrophy genes showed an association with disease-related intermediate phenotypic traits among diabetics but not in the control group. We also attempted to individualize the diabetic patients based on ±2 fold altered expression of lipodystrophy genes as compared to their average expression in the control group. In conclusion, significant overlap exists between some of the lipodystrophy genes and their network with DEGs in the peripheral adipose tissue in diabetics. They possibly play a role in the pathogenesis of diabetes and individualization of diabetics is possible based on their altered expression in their peripheral adipose tissue.

Keywords: Lipodystrophy; WGCNA; network biology; type 2 diabetes.

MeSH terms

  • Adipose Tissue / metabolism*
  • Aged
  • Asian People / genetics
  • Class Ia Phosphatidylinositol 3-Kinase / genetics
  • Class Ia Phosphatidylinositol 3-Kinase / metabolism
  • Cross-Sectional Studies
  • Diabetes Mellitus, Type 2 / genetics
  • Diabetes Mellitus, Type 2 / pathology*
  • Down-Regulation
  • Female
  • Gene Regulatory Networks
  • Humans
  • India
  • Leukocyte Common Antigens / genetics
  • Leukocyte Common Antigens / metabolism
  • Lipodystrophy / genetics
  • Lipodystrophy / pathology*
  • Male
  • Middle Aged
  • PPAR alpha / genetics
  • PPAR alpha / metabolism
  • Phenotype
  • SUMO-1 Protein / genetics
  • SUMO-1 Protein / metabolism
  • Transcriptome*
  • Up-Regulation

Substances

  • PPAR alpha
  • PPARA protein, human
  • SUMO-1 Protein
  • SUMO1 protein, human
  • PIK3R1 protein, human
  • Class Ia Phosphatidylinositol 3-Kinase
  • Leukocyte Common Antigens
  • PTPRC protein, human

Supplementary concepts

  • Lipodystrophy, Partial, Acquired

Grants and funding

Financial grant received from the Indian Council of Medical Research, Government of India is gratefully acknowledged [Grant no 5/4/8/2012-RMC].