Reduced branched-chain aminotransferase activity alleviates metabolic vulnerability caused by dim light exposure at night in Drosophila

Nov 23, 2022Journal of neurogenetics

Lower activity of a key amino acid enzyme reduces metabolism problems from nighttime dim light in fruit flies

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Abstract

Exposure to dim light at night (10 lux) alters sleep-wake behavior and metabolism in male wild-type flies.

Dim light exposure disrupted the 24-hour sleep-wake cycle and circadian rhythm gene expression.
Flies became more vulnerable to metabolic stress, such as starvation, following dim light exposure.
Analysis showed decreased levels of branched-chain amino acids (BCAAs), including isoleucine and valine, in exposed flies.
Increased expression of enzymes that regulate BCAA metabolism was observed in flies exposed to dim light.
A heterozygous mutation protected flies from starvation stress, maintaining their BCAA levels despite dim light exposure.
Feeding BCAAs to wild-type flies reversed their metabolic vulnerability caused by dim light.

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The rhythmic pattern of biological processes controlled by light over 24 h is termed the circadian rhythm. Disturbance of circadian rhythm due to exposure to light at night (LAN) disrupts the sleep-wake cycle and can promote cardiovascular disease, diabetes, cancer, and metabolic disorders in humans. We studied how dim LAN affects the circadian rhythm and metabolism using male. Wild-type flies exposed to the dim light of 10 lux at night displayed altered 24 h sleep-wake behavior and expression patterns of circadian rhythm genes. In addition, the flies became more vulnerable to metabolic stress, such as starvation. Whole-body metabolite analysis revealed decreased amounts of branched-chain amino acids (BCAAs), such as isoleucine and valine. The dim light exposure also increased the expression of branched-chain amino acid aminotransferase (BCAT) and branched-chain α-keto acid dehydrogenase (BCKDC) enzyme complexes that regulate the metabolism of BCAAs. Flies with theheterozygous mutation were not vulnerable to starvation stress, even when exposed to dim LAN, and hemolymph BCAA levels did not decrease in these flies. Furthermore, the vulnerability to starvation stress was also suppressed when theexpression level was reduced in the whole body, neurons, or fat body during adulthood using conditional GAL4 and RNA interference. Finally, the metabolic vulnerability was reversed when BCAAs were fed to wild-type flies exposed to LAN. Thus, short-term dim light exposure at night affects the expression of circadian genes and BCAA metabolism in, implying a novel function of BCAAs in suppressing metabolic stress caused by disrupted circadian rhythm. Drosophila Bcat Bcat Drosophila

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Reduced branched-chain aminotransferase activity alleviates metabolic vulnerability caused by dim light exposure at night in Drosophila

Abstract

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