Progression from high insulin resistance to type 2 diabetes does not entail additional visceral adipose tissue inflammation

PLoS One. 2012;7(10):e48155. doi: 10.1371/journal.pone.0048155. Epub 2012 Oct 24.

Abstract

Obesity is associated with a low-grade chronic inflammation state. As a consequence, adipose tissue expresses pro-inflammatory cytokines that propagate inflammatory responses systemically elsewhere, promoting whole-body insulin resistance and consequential islet β-cell exhaustation. Thus, insulin resistance is considered the early stage of type 2 diabetes. However, there is evidence of obese individuals that never develop diabetes indicating that the mechanisms governing the association between the increase of inflammatory factors and type 2 diabetes are much more complex and deserve further investigation. We studied for the first time the differences in insulin signalling and inflammatory pathways in blood and visceral adipose tissue (VAT) of 20 lean healthy donors and 40 equal morbidly obese (MO) patients classified in high insulin resistance (high IR) degree and diabetes state. We studied the changes in proinflammatory markers and lipid content from serum; macrophage infiltration, mRNA expression of inflammatory cytokines and transcription factors, activation of kinases involved in inflammation and expression of insulin signalling molecules in VAT. VAT comparison of these experimental groups revealed that type 2 diabetic-MO subjects exhibit the same pro-inflammatory profile than the high IR-MO patients, characterized by elevated levels of IL-1β, IL-6, TNFα, JNK1/2, ERK1/2, STAT3 and NFκB. Our work rules out the assumption that the inflammation should be increased in obese people with type 2 diabetes compared to high IR obese. These findings indicate that some mechanisms, other than systemic and VAT inflammation must be involved in the development of type 2 diabetes in obesity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Diabetes Mellitus, Type 2 / immunology*
  • Female
  • Humans
  • Inflammation / physiopathology*
  • Insulin Resistance / physiology*
  • Interleukin-1beta / metabolism
  • Interleukin-6 / metabolism
  • Intra-Abdominal Fat / immunology*
  • JNK Mitogen-Activated Protein Kinases / metabolism
  • Male
  • Mitogen-Activated Protein Kinase 1 / metabolism
  • Mitogen-Activated Protein Kinase 3 / metabolism
  • NF-kappa B / metabolism
  • Obesity, Morbid / immunology
  • Obesity, Morbid / metabolism
  • STAT3 Transcription Factor / metabolism
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • Interleukin-1beta
  • Interleukin-6
  • NF-kappa B
  • STAT3 Transcription Factor
  • STAT3 protein, human
  • Tumor Necrosis Factor-alpha
  • JNK Mitogen-Activated Protein Kinases
  • Mitogen-Activated Protein Kinase 1
  • Mitogen-Activated Protein Kinase 3

Grants and funding

This work was supported by the Junta de Andalucia, (grant number P08-CTS-04369) and the Fondo de Investigación Sanitaria (grant number PS09/00997), Spain. NB was supported by a “Sara Borrell” postdoctoral contract from the “Instituto de Salud Carlos III”, Spain. LGS was supported by a “Juan de la Cierva (JCI-2009-04086)” postdoctoral contract. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.