Abstract
Circadian rhythms are ~24 h fluctuations of different biological processes that are regulated by the circadian clock system. They exert a major influence on most of the metabolism, such as the hepatic metabolism. This rhythmicity can be disrupted by obesogenic diets, fact that is considered to be a risk factor for the development of metabolic diseases. Nevertheless, obesogenic diets do not affect both genders in the same manner. We hypothesized that the circadian rhythms disruption of the hepatic metabolism, caused by obesogenic diets, is gender-dependent. Male and female Fischer 344 rats were fed either a standard diet or a cafeteria diet and sacrificed at two different moments, at zeitgeber 3 and 15. Only female rats maintained the circadian variations of the hepatic metabolism under a cafeteria diet. Most of those metabolites were related with the very low density lipoprotein (VLDL) synthesis, such as choline, betaine or phosphatidylcholine. Most of these metabolites were found to be increased at the beginning of the dark period. On the other hand, male animals did not show these time differences. These findings suggest that females might be more protected against the circadian disruption of the hepatic metabolism caused by a cafeteria diet through the increase of the VLDL synthesis at the beginning of the feeding time.
Highlights
Almost all mammalian cell types express clock genes and are synchronized by the circadian clock system, which is located in the suprachiasmatic nucleus (SCN) of the hypothalamus and ensures that internal physiology is synchronized with the external environment [1]
The model significance was p < 0.001, which confirms the model validity. These results indicated that male rats were more susceptible to the disruption of the homeostatic equilibrium of the hepatic metabolism induced by an obesogenic diet than female rats
Once we determined that the hepatic metabolism has circadian rhythmicity due to the differences observed in the homeostatic equilibrium, we further studied which specific metabolites showed differences between ZT3 and ZT15 and whether these characteristic metabolite changes were specific to gender and/or could be modified by an obesogenic diet (Supplementary Tables S2–S5)
Summary
Almost all mammalian cell types express clock genes and are synchronized by the circadian clock system, which is located in the suprachiasmatic nucleus (SCN) of the hypothalamus and ensures that internal physiology is synchronized with the external environment [1]. Most of the hepatic metabolisms present circadian rhythms [2]. In this sense, glucose and lipid metabolism is subjected to a time circadian control [3,4,5]. Glucagon and insulin, synthesized in and released from pancreatic α and β cells, regulate these pathways, and daily plasma rhythms in these hormones have been identified in rodents and humans [6]. Bile acids are synthesized from cholesterol exclusively in the liver by the rate-limiting enzyme cholesterol 7α-hydroxylase (CYP7A1), and it exhibits a well-documented rhythm of mRNA expression in rodents and an enzyme activity in human serum [8,9].
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