Resveratrol reversed ambient particulate matter exposure-perturbed oscillations of hepatic glucose metabolism by regulating SIRT1 in mice

Dec 2, 2022Environmental science and pollution research international

Resveratrol may restore disrupted liver sugar metabolism caused by air pollution in mice through SIRT1 regulation

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Abstract

Long-term exposure to ambient particulate matter (PM) for 15 weeks disrupted the hepatic circadian clock and glucose metabolism in mice.

PM exposure induced glucose metabolism disorder in C57BL/6 mice.
The rhythmic expression of core clock genes and their target genes related to glucose metabolism was perturbed.
Ambient PM exposure significantly altered the expression patterns of key proteins such as BMAL1 and SIRT1.
Supplementation with resveratrol (RES) reversed the rhythm misalignment of BMAL1 and clock genes and improved glucose metabolism.
RES also restored the SIRT1 circadian rhythm in liver cells affected by PM exposure.

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Much evidence has shown that ambient particulate matter (PM) exposure is associated with abnormal glucose metabolism, but the underlying mechanism has not yet been fully characterized. Circadian disruption has adverse effects on glucose metabolism. In this study, we investigated the effects of long-term ambient PM exposure on the hepatic circadian clock and the expression rhythm of genes associated with hepatic glucose metabolism in mice. C57BL/6 mice were exposed to filtered air (FA), ambient PM, or ambient PM plus resveratrol (RES). After 15 weeks (12 h per day, 7 days per week) of exposure, glucose homeostasis, the rhythmic expression of clock genes, and genes associated with hepatic glucose metabolism were determined. Our results found that PM exposure induced glucose metabolism disorder and perturbed the rhythmic mRNA expression of core clock genes and their target genes involved in hepatic glucose metabolism. Mechanistic investigations demonstrated that ambient PM exposure markedly altered the expression patterns of BMAL1, clock, and SIRT1 in vivo. Simultaneously, we demonstrated that RES (an activator of SIRT1) changed the expression pattern of SIRT1, thereby reversing the rhythm misalignment of BMAL1 and clock and hepatic glucose metabolism disorder induced by ambient PM exposure. In addition, PMexposure perturbed the rhythmic protein expression of BMAL1, clock, and SIRT1 in L-02 cells. Simultaneously, we demonstrated that RES restored the SIRT1 circadian rhythm, which reversed the rhythm misalignment of BMAL1 and clock in L-02 cells induced by PMexposure. Taken together, our results suggested that long-term ambient PM exposure perturbed the hepatic core circadian clock rhythm and caused glucose metabolism disorder, which could be reversed by RES supplementation. Our study offers a potential application of RES for combating circadian misalignment-related metabolic diseases. 2.5 2.5

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Resveratrol reversed ambient particulate matter exposure-perturbed oscillations of hepatic glucose metabolism by regulating SIRT1 in mice

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