Chronic inflammatory diseases, e.g., obesity, cardiovascular disease and type-2 diabetes, progressively suppress the anti-inflammatory heat shock response (HSR) by impairing the synthesis of key components, perpetuating inflammation. Monitoring HSR progression offers predictive value for countering chronic inflammation. This study quantified HSR in high-fat diet (HFD) and normal chow (NC) mice by measuring 70 kDa heat shock protein (HSP70) expression after heat treatment of whole blood samples. To align with human translational relevance, animals were housed within their thermoneutral zone (TNZ). Whole blood was heat-challenged weekly at 42 °C for 1–2 hours over 22 weeks, and ΔHSP70 was calculated as the difference between HSP70 expressions at 42 °C and 37 °C. Results correlated with fasting glycaemia, oral glucose tolerance test, intraperitoneal insulin tolerance test and 2-hour post-glucose load glycaemia. ΔHSP70 levels >0.2250 indicated normal fasting glycaemia, while levels <0.2125 signalled insulin resistance and type-2 diabetes onset. A logistic model (five-parameter logistic) showed progressive HSR decline, with HFD mice exhibiting earlier ΔHSP70 reduction (t1/2 = 3.14 weeks) compared with NC mice (t1/2 = 8.24 weeks), highlighting compromised anti-inflammatory capacity in both groups of mice maintained at TNZ. Remarkably, even NC mice surpassed insulin resistance thresholds by week 22, relevant as control diets confronted interventions. Observed HSR decline mirrors tissue-level suppression in obese and type-2 diabetic individuals, underscoring HSR failure as a hallmark of obesity-driven inflammation. This study introduces a practical whole-blood assay to evaluate HSR suppression, allowing assessment of glycaemic status during obesity onset before any clinical manifestation.
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Research Article|
January 23 2025
Early detection and progression of insulin resistance revealed by impaired organismal anti-inflammatory heat shock response during ex vivo whole-blood heat challenge
Helena Trevisan Schroeder
;
Helena Trevisan Schroeder
(Conceptualization, Data curation, Formal analysis, Validation, Investigation, Visualization, Methodology, Writing - original draft, Writing - review & editing)
1Laboratory of Cellular Physiology (FisCel), Department of Physiology, Institute of Basic Health Sciences (ICBS), Federal University of Rio Grande do Sul (UFRGS), Rua Ramiro Barcelos 2600, laboratory 646, 90035-003 Porto Alegre, RS, Brazil
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Carlos Henrique de Lemos Muller
;
Carlos Henrique de Lemos Muller
(Resources, Data curation, Formal analysis, Validation, Investigation, Visualization, Methodology, Writing - original draft)
1Laboratory of Cellular Physiology (FisCel), Department of Physiology, Institute of Basic Health Sciences (ICBS), Federal University of Rio Grande do Sul (UFRGS), Rua Ramiro Barcelos 2600, laboratory 646, 90035-003 Porto Alegre, RS, Brazil
2Laboratory of Inflammation, Metabolism and Exercise Research (LAPIMEX), Department of Physiology, ICBS, UFRGS, 90035-003 Porto Alegre, RS, Brazil
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Maria Inês Lavina Rodrigues
;
Maria Inês Lavina Rodrigues
(Resources, Data curation, Formal analysis, Validation, Investigation, Visualization, Methodology)
1Laboratory of Cellular Physiology (FisCel), Department of Physiology, Institute of Basic Health Sciences (ICBS), Federal University of Rio Grande do Sul (UFRGS), Rua Ramiro Barcelos 2600, laboratory 646, 90035-003 Porto Alegre, RS, Brazil
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Marcela Alves de Azevedo
;
Marcela Alves de Azevedo
(Formal analysis, Validation, Investigation, Visualization, Methodology)
1Laboratory of Cellular Physiology (FisCel), Department of Physiology, Institute of Basic Health Sciences (ICBS), Federal University of Rio Grande do Sul (UFRGS), Rua Ramiro Barcelos 2600, laboratory 646, 90035-003 Porto Alegre, RS, Brazil
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Thiago Gomes Heck
;
Thiago Gomes Heck
(Resources, Data curation, Formal analysis, Supervision, Funding acquisition, Validation, Investigation, Visualization, Methodology, Writing - review & editing)
3Postgraduate Program in Integral Health Care (PPGAIS-UNIJUÍ/UNICRUZ/URI), Regional University of Northwestern Rio Grande Do Sul State (UNIJUI), 98700-000 Ijuí, RS, Brazil
4Postgraduate Program in Mathematical and Computational Modelling (PPGMMC), UNIJUI, 98700-000 Ijuí, RS, Brazil
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Mauricio Krause
;
Mauricio Krause
(Conceptualization, Resources, Data curation, Formal analysis, Supervision, Funding acquisition, Validation, Investigation, Visualization, Methodology, Writing - original draft)
2Laboratory of Inflammation, Metabolism and Exercise Research (LAPIMEX), Department of Physiology, ICBS, UFRGS, 90035-003 Porto Alegre, RS, Brazil
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Paulo Ivo Homem de Bittencourt Jr.
(Conceptualization, Resources, Data curation, Formal analysis, Supervision, Funding acquisition, Validation, Investigation, Visualization, Methodology, Writing - original draft, Project administration, Writing - review & editing)
1Laboratory of Cellular Physiology (FisCel), Department of Physiology, Institute of Basic Health Sciences (ICBS), Federal University of Rio Grande do Sul (UFRGS), Rua Ramiro Barcelos 2600, laboratory 646, 90035-003 Porto Alegre, RS, Brazil
Correspondence: Paulo Ivo Homem de Bittencourt Jr. ([email protected])
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Publisher: Portland Press Ltd
Received:
December 14 2024
Revision Received:
December 20 2024
Accepted:
December 23 2024
Online ISSN: 1470-8736
Print ISSN: 0143-5221
© 2025 The Author(s); published by Portland Press Limited on behalf of the Biochemical Society.
2025
Clin Sci (Lond) (2025) 139 (02): 85–113.
Article history
Received:
December 14 2024
Revision Received:
December 20 2024
Accepted:
December 23 2024
Citation
Helena Trevisan Schroeder, Carlos Henrique de Lemos Muller, Maria Inês Lavina Rodrigues, Marcela Alves de Azevedo, Thiago Gomes Heck, Mauricio Krause, Paulo Ivo Homem de Bittencourt Jr.; Early detection and progression of insulin resistance revealed by impaired organismal anti-inflammatory heat shock response during ex vivo whole-blood heat challenge. Clin Sci (Lond) 28 January 2025; 139 (02): 85–113. doi: https://doi.org/10.1042/CS20243515
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