Hyperglycemia activates caspase-1 and TXNIP-mediated IL-1beta transcription in human adipose tissue

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

• Level A · Stronger Clinical Evidence
• Level B · Emerging clinical evidence with positive signals
• Level C · Early human research exploring benefits
• Level D · Scientific groundwork from lab and animal studies
• Emerging · Emerging topic under active research

Abstract (original English)

Objective Obesity is characterized by elevated levels of proinflammatory cytokines, including interleukin (IL)-1β, that contribute to the development of insulin resistance. In this study, we set out to investigate whether hyperglycemia drives IL-1β production and caspase-1 activation in murine and human adipose tissue, thus inducing insulin resistance. Research design and methods ob/ob animals were used as a model to study obesity and hyperglycemia. Human adipose tissue fragments or adipocytes were cultured in medium containing normal or high glucose levels. Additionally, the role of thioredoxin interacting protein (TXNIP) in glucose-induced IL-1β production was assessed. Results TXNIP and caspase-1 protein levels were more abundantly expressed in adipose tissue of hyperglycemic ob/ob animals as compared with wild-type mice. In human adipose tissue, high glucose resulted in a 10-fold upregulation of TXNIP gene expression levels (P Conclusions High glucose activates caspase-1 in human and murine adipose tissue. Glucose-induced activation of TXNIP mediates IL-1β mRNA expression levels and intracellular pro-IL-1β accumulation in adipose tissue. The concerted actions lead to enhanced secretion of IL-1β in adipose tissue that may contribute to the development of insulin resistance.

Evidence level

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

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