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[Preprint]. 2024 Jun 24:rs.3.rs-4548154.
doi: 10.21203/rs.3.rs-4548154/v1.

The impact of heat stress on the human plasma lipidome

Igor L Estevao  1 , Josh B Kazman  2 , Lisa M Bramer  1 , Carrie Nicora  1 , Ming Qiang Ren  2 , Nyamkhishig Sambuughin  2 , Nathalie Munoz  1 , Young-Mo Kim  1 , Kent Bloodsworth  1 , Maile Richert  2 , Justin Teeguarden  1 , Kristin Burnum-Johnson  1 , Patricia A Deuster  2 , Ernesto S Nakayasu  1 , Gina Many  1
Affiliations

The impact of heat stress on the human plasma lipidome

Igor L Estevao et al. Res Sq. .

Update in

  • The human plasma lipidome response to exertional heat tolerance testing.
    Estevao IL, Kazman JB, Bramer LM, Nicora C, Ren MQ, Sambuughin N, Munoz N, Kim YM, Bloodsworth K, Richert M, Teeguarden J, Burnum-Johnson K, Deuster PA, Nakayasu ES, Many G. Estevao IL, et al. Lipids Health Dis. 2024 Nov 15;23(1):380. doi: 10.1186/s12944-024-02322-7. Lipids Health Dis. 2024. PMID: 39548465 Free PMC article.

Abstract

The year of 2023 displayed the highest average global temperatures since it has been recorded-the duration and severity of extreme heat are projected to increase. Rising global temperatures represent a major public health threat, especially to occupations exposed to hot environments, such as construction and agricultural workers, and first responders. Despite efforts of the scientific community, there is still a need to characterize the pathophysiological processes leading to heat related illness and develop biomarkers that can predict its onset. Here, we performed a plasma lipidomic analysis on male and female subjects who underwent heat tolerance testing (HTT), consisting of a 2-h treadmill walk at 5 km/h with 2% inclination at a controlled temperature of 40°C. We identified 995 lipids from 27 classes, with nearly half of all detected lipids being responsive to HTT. Lipid classes related to substrate utilization were predominantly affected by HTT, with a downregulation of triacylglycerols and upregulation of free fatty acids and acyl-carnitines (CARs). We additionally examined correlations between changes in plasma lipids by using the physiological strain index (PSI). Here, even chain CAR 4:0, 14:0 and 16:1, suggested by-products of incomplete beta oxidation, and diacylglycerols displayed the highest correlation to PSI. PSI did not correlate with plasma lactate levels, suggesting that correlations between even chain CARs and PSI is related to metabolic efficiency versus physical exertion. Overall, our results show that HTT has a strong impact on the plasma lipidome and that metabolic inefficiencies may underlie heat intolerance.

Keywords: Heat stress; biomarkers; heat tolerance testing; plasma lipidomics.

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Conflict of interest statement

Competing interests The authors declare that they have no competing interests.

Figures

Figure 1
Figure 1. Effects of exertional heat stress on the plasma lipidome.
(A) volcano plot displaying the number of differentially regulated plasma lipid species following heat tolerance testing, where each dot represents an individual lipid species. Upregulated species are indicated by red, downregulated in blue and non-significant (NS). (B) Distribution of up- (red) and down-regulated (blue) lipids species according to class Class enrichment was assessed by Fisher’s exact test; p-values ≤ 0.05 are represented by asterisks (*).
Figure 2
Figure 2. Changes in triacylglycerol species distribution following exertional heat tolerance testing.
Changes in the triacylglycerol species distribution. A Linear regression curve was analyzed on log2 fold change values with exertion heat stress testing according to (A) carbon chain length and (B) double bond content.
Figure 3
Figure 3. Differences in lipidomic responses to exertion heat stress testing between males and females.
A. The number of plasma lipids displaying a by sex and timepoint interaction. Non-significant (NS) lipids (grey) represent those that are impacted by sex but did not change significantly with heat tolerance testing. Statistically significant down- and upregulated lipids that displayed a by sex and timepoint interaction are shown in blue and red, respectively. B-F. Box plots representing select lipid species from Fig. 3A. G. Network of individual lipid species and their corresponding lipid class that are significantly impacted by sex. Blue oval represents lipid species (LS) downregulated in both males and females, light turquoise color represents LS downregulated in females only, grey oval represents NS lipid species, light red represents upregulated LS in females only, and dark red oval indicates upregulated LS in males (M) and females (F). Light green rhombus is representative of a lipid class not significantly enriches, while a dark green rhombus is representative of enriched lipid classes.
Figure 4
Figure 4. Computational network analysis of plasma lipid correlates to physiological strain index during heat tolerance testing.
Visualization of positive (red rhombus) and negative (blue rhombus) enriched lipid classes. Correlation score in red/blue color saturation on lipid species represents fold change.
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