Lymphocyte roles in metabolic dysfunction: Of men and mice

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.