Abstract
A major complication of heat-related illness is the development of acute kidney injury (AKI) and damage to kidney tubular cells. Because kidney tubular cells utilize fatty acids as a major energy source, impaired fatty acid oxidation (FAO) may be associated with kidney injury due to heat stress. Carnitine is essential in the transportation of fatty acid into mitochondria for FAO. To date, there has been little attention given to the role of carnitine in heat-related illness and AKI. To evaluate the relationship between carnitine inadequacy and heat-related illness severity or AKI, we examined serum carnitine levels in patients with heat-related illness. We also used heat-stressed mice, to investigate the effect of L-carnitine pre-treatment on various kidney functions such as mitochondrial activity, proinflammatory changes in kidney macrophages, and histological damage. We observed an elevation in serum acylcarnitine levels, indicating carnitine insufficiency in patients with severe heat-related illness and/or AKI. L-carnitine pretreatment ameliorated ATP production in murine tubular cell mitochondria and prevented a change in the kidney macrophage population dynamics observed in AKI - a decrease in tissue resident macrophages, influx of bone marrow-derived macrophages, and change toward pro-inflammatory M1 polarization. In conclusion, carnitine insufficiency may be closely associated with severe heat-related illness and related AKI. Enhancement of the FAO pathway by L-carnitine pretreatment may prevent heat stress-induced AKI by restoring mitochondrial function.
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