Lymphocyte roles in metabolic dysfunction: of men and mice

Trends Endocrinol Metab. 2015 Feb;26(2):91-100. doi: 10.1016/j.tem.2014.12.001. Epub 2015 Jan 5.


Type 2 diabetes (T2D) is a metabolic disease associated with obesity-related insulin resistance (IR) and chronic inflammation. Animal studies indicate that IR can be caused and/or exacerbated by systemic and/or tissue-specific alterations in lymphocyte differentiation and function. Human studies also indicate that obesity-associated inflammation promotes IR. Nevertheless, clinical trials with anti-inflammatory therapies have yielded modest impacts on established T2D. Unlike mouse models, where obesity is predominantly associated with IR, 20-25% of obese humans are metabolically healthy with high insulin sensitivity. The uncoupling of obesity from IR in humans but not in animal models advocates for a more comprehensive understanding of mediators and mechanisms of human obesity-promoted IR, and better integration of knowledge from human studies into animal experiments to efficiently pursue T2D prevention and treatment.

Keywords: insulin resistance; lymphocyte subsets; obesity; type 2 diabetes.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Adipocytes / immunology
  • Adipocytes / metabolism
  • Animals
  • Diabetes Mellitus, Type 2 / complications
  • Diabetes Mellitus, Type 2 / immunology
  • Diabetes Mellitus, Type 2 / metabolism
  • Humans
  • Inflammation / immunology
  • Inflammation / metabolism
  • Lymphocytes / physiology*
  • Male
  • Metabolic Diseases / immunology*
  • Mice
  • Obesity / complications
  • Obesity / immunology
  • Obesity / metabolism