Early detection and progression of insulin resistance revealed by impaired organismal anti-inflammatory heat shock response during ex vivo whole-blood heat challenge

• DOI: 10.1042/cs20243515
• Publication Date: 2024-12-24T06:25:32Z
• Authors: Helena Trevisan S...; Carlos Henrique d...; Maria Inês Lavina...; Marcela Alves de ...; Thiago Gomes Heck; Mauricio Krause; Paulo Ivo Homem d...
• Keywords: Ex vivo

Chronic inflammatory diseases, e.g., obesity, cardiovascular disease, and type 2 diabetes, progressively suppress the anti-inflammatory heat shock response (HSR) by impairing synthesis of key components, perpetuating inflammation. Monitoring HSR progression offers predictive value for countering chronic This study quantified in high-fat diet (HFD) normal chow (NC) mice measuring 70 kDa protein (HSP70) expression after treatment whole blood samples. To align with human translational relevance, animals were housed within their thermoneutral zone (TNZ). Whole was heat-challenged weekly at 42 °C 1-2 hours over 22 weeks, ΔHSP70 calculated as difference between HSP70 expressions 37 °C. Results correlated fasting glycaemia, oral glucose tolerance test (oGTT), intraperitoneal insulin (ipITT), 2-hour post-glucose load glycaemia. levels >0.2250 indicated while 1/2 = 3.14 weeks) compared to NC (t1/2 8.24 weeks), highlighting compromised capacity both groups maintained TNZ. Remarkably, even surpassed resistance thresholds week 22, relevant control diets confronted interventions. Observed decline mirrors tissue-level suppression obese diabetic individuals, underscoring failure a hallmark obesity-driven introduces practical whole-blood assay evaluate allowing assessment glycaemic status during obesity onset before any clinical manifestation.