Family history of diabetes is associated with enhanced adipose lipolysis: Evidence for the implication of epigenetic factors

Diabetes Metab. 2018 Mar;44(2):155-159. doi: 10.1016/j.diabet.2017.10.010. Epub 2017 Nov 11.

Abstract

Aims: Type 2 diabetes is associated with insulin resistance, adipose hypertrophy and increased lipolysis. The heritability of these traits has been determined by associating them with a family history of diabetes.

Methods: Abdominal subcutaneous fat biopsies were obtained from 581 subjects in a cross-sectional study. Fat cells were isolated, and the difference between measured and expected fat-cell volume was used to determine adipose morphology (degree of hypertrophy or hyperplasia). Spontaneous lipolytic activity was determined in explants of adipose tissue by measuring glycerol release. Insulin-stimulated lipogenesis was assessed by measuring the incorporation of radiolabelled glucose into fat-cell lipids. Information on parental history of diabetes was gathered by a questionnaire.

Results: Adipose morphology correlated positively with lipolysis (P<0.0001) and inversely with insulin-stimulated lipogenesis (P<0.008). Also, 24% of probands had a family history of diabetes, which was associated with higher body mass index (BMI) scores, and more insulin resistance (HOMAIR) and adipose hypertrophy. Lipolytic activity was increased, and insulin-stimulated lipogenesis decreased, in probands with a parental history of diabetes. The results for HOMAIR, lipolysis and adipose morphology remained significant after adjusting for proband BMI. A maternal history of diabetes was associated with increased adipose lipolytic activity in probands.

Conclusion: A family history of diabetes is independent of proband BMI, but associated with adipocyte hypertrophy and enhanced lipolysis, which suggests that these factors are genetically linked to diabetes. Moreover, the influence on lipolysis was only observed in probands with a maternal history of diabetes, thereby supporting an epigenetic impact.

Keywords: Epidemiology; Fat cell; Lipolysis; Type 2 diabetes.

MeSH terms

  • Abdominal Fat / cytology
  • Abdominal Fat / drug effects
  • Adipocytes / cytology
  • Adipocytes / drug effects
  • Adolescent
  • Adult
  • Aged
  • Biopsy
  • Cells, Cultured
  • Diabetes Mellitus, Type 2 / epidemiology*
  • Diabetes Mellitus, Type 2 / physiopathology*
  • Epigenesis, Genetic
  • Female
  • Humans
  • Hypertrophy
  • Insulin / pharmacology
  • Lipogenesis / drug effects*
  • Lipolysis / drug effects*
  • Male
  • Medical History Taking
  • Middle Aged
  • Subcutaneous Fat / cytology
  • Subcutaneous Fat / drug effects
  • Young Adult

Substances

  • Insulin