Increased fat cell size: a major phenotype of subcutaneous white adipose tissue in non-obese individuals with type 2 diabetes

Diabetologia. 2016 Mar;59(3):560-70. doi: 10.1007/s00125-015-3810-6. Epub 2015 Nov 25.


Aims/hypothesis: We aimed to elucidate the impact of fat cell size and inflammatory status of adipose tissue on the development of type 2 diabetes in non-obese individuals.

Methods: We characterised subcutaneous abdominal adipose tissue by examining stromal cell populations by 13 colour flow cytometry, measuring expression of adipogenesis genes in the progenitor cell fraction and determining lipolysis and adipose secretion of inflammatory proteins in 14 non-obese men with type 2 diabetes and 13 healthy controls matched for age, sex, body weight and total fat mass.

Results: Individuals with diabetes had larger fat cells than the healthy controls but stromal cell population frequencies, adipose lipolysis and secretion of inflammatory proteins did not differ between the two groups. However, in the entire cohort fat cell size correlated positively with the ratio of M1/M2 macrophages, TNF-α secretion, lipolysis and insulin resistance. Expression of genes encoding regulators of adipogenesis and adipose morphology (BMP4, CEBPα [also known as CEBPA], PPARγ [also known as PPARG] and EBF1) correlated negatively with fat cell size.

Conclusions/interpretation: We show that a major phenotype of white adipose tissue in non-obese individuals with type 2 diabetes is adipocyte hypertrophy, which may be mediated by an impaired adipogenic capacity in progenitor cells. Consequently, this could have an impact on adipose tissue inflammation, release of fatty acids, ectopic fat deposition and insulin sensitivity.

Keywords: Adipocyte hypertrophy; Non-obese; Subcutaneous adipose; Type 2 diabetes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipocytes / metabolism*
  • Adipocytes / pathology*
  • Adipose Tissue, White / metabolism*
  • Adipose Tissue, White / pathology*
  • Adult
  • Aged
  • Case-Control Studies
  • Diabetes Mellitus, Type 2 / metabolism*
  • Diabetes Mellitus, Type 2 / pathology*
  • Female
  • Humans
  • Insulin / metabolism
  • Insulin Resistance / physiology
  • Lipolysis / physiology
  • Macrophages / metabolism
  • Macrophages / physiology
  • Male
  • Middle Aged
  • Obesity / metabolism
  • Obesity / pathology
  • Subcutaneous Fat / metabolism*
  • Subcutaneous Fat / pathology*
  • Tumor Necrosis Factor-alpha / metabolism


  • Insulin
  • Tumor Necrosis Factor-alpha