Circadian rhythm–dependent induction of hepatic lipogenic gene expression in rats fed a high-sucrose diet

Journal of Biological Chemistry(2019)

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Metabolic syndrome has become a global health challenge and was recently reported to be positively correlated with increased sucrose consumption. Mechanistic analyses of excess sucrose-induced progression of metabolic syndrome have been focused mainly on abnormal hepatic lipogenesis, and the exact contribution of excess sucrose to metabolic disorders remains controversial. Considering that carbohydrate and lipid metabolisms exhibit clear circadian rhythms, here we investigated the possible contribution of diurnal oscillations to responses of hepatic lipid metabolism to excess sucrose. We found that excess sucrose dose-dependently promotes fatty liver and hyperlipidemia in in rats fed a high-sucrose diet (HSD). We observed that excess sucrose enhances the oscillation amplitudes of the expression of clock genes along with the levels of hepatic lipid and carbohydrate metabolism-related mRNAs that increase lipogenesis. We did not observe similar changes in the levels of the transcription factors regulating the expression of these genes. This suggested that the excess sucrose-induced, circadian rhythm?dependent amplification of lipogenesis is post-transcriptionally regulated via the stability of metabolic gene transcripts. Of note, our findings also provide evidence that fructose causes some of the HSD-induced, circadian rhythm?dependent alterations in lipogenic gene expression. Our discovery of HSD-induced circadian rhythm?dependent alterations in lipogenesis at the post-transcriptional level may inform future studies investigating the complex relationships among sucrose uptake, circadian rhythm, and metabolic enzyme expression. Our findings could contribute to the design of chrono-nutritional interventions to prevent or manage the development of fatty liver and hyperlipidemia in sucrose-induced metabolic syndrome.
metabolic syndrome,fatty acid metabolism,circadian rhythm,dyslipidemia,lipogenesis,excess sucrose intake,nonalcoholic fatty liver diseases,lipid metabolic disorders,high-sucrose diet (HSD),gene regulation
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