The outliers become a stampede as immunometabolism reaches a tipping point.
Obesity and Type 2 diabetes mellitus (T2D) are characterized by pro-inflammatory alterations in the immune system including shifts in leukocyte subset differentiation and in cytokine/chemokine balance. The chronic, low-grade inflammation resulting largely from changes in T-cell, B-cell, and myeloid compartments promotes and/or exacerbates insulin resistance (IR) that, together with pancreatic islet failure, defines T2D. Animal model studies show that interruption of immune cell-mediated inflammation by any one of several methods almost invariably results in the prevention or delay of obesity and/or IR. However, anti-inflammatory therapies have had a modest impact on established T2D in clinical trials. These seemingly contradictory results indicate that a more comprehensive understanding of human IR/T2D-associated immune cell function is needed to leverage animal studies into clinical treatments. Important outstanding analyses include identifying potential immunological checkpoints in disease etiology, detailing immune cell/adipose tissue cross-talk, and defining strengths/weaknesses of model organism studies to determine whether we can harness the promising new field of immunometabolism to curb the global obesity and T2D epidemics.
Department of Microbiology, Boston University, Boston, MA 02118, USA. bnikol@bu.edu
Barbara S
BS
Nikolajczyk
Madhumita
M
Jagannathan-Bogdan
Gerald V
GV
Denis
D017667:Adipocytes / Q000276:immunology; D000273:Adipose Tissue / Q000276:immunology / Q000378:metabolism; D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology; D002454:Cell Differentiation; D003924:Diabetes Mellitus, Type 2 / Q000276:immunology* / Q000378:metabolism*; D004734:Energy Metabolism; D006801:Humans; D007249:Inflammation / Q000276:immunology; D007333:Insulin Resistance; D007962:Leukocytes / Q000276:immunology; D051379:Mice; D009765:Obesity / Q000276:immunology / Q000378:metabolism*; D013601:T-Lymphocytes / Q000276:immunology