Abstract
Major susceptibility to alterations in liver function (e.g., hepatic steatosis) in a prone environment due to circadian misalignments represents a common consequence of recent sociobiological behavior (i.e., food excess and sleep deprivation). Natural compounds and, more concisely, polyphenols have been shown as an interesting tool for fighting against metabolic syndrome and related consequences. Furthermore, mitochondria have been identified as an important target for mediation of the health effects of these compounds. Additionally, mitochondrial function and dynamics are strongly regulated in a circadian way. Thus, we wondered whether some of the beneficial effects of grape-seed procyanidin extract (GSPE) on metabolic syndrome could be mediated by a circadian modulation of mitochondrial homeostasis. For this purpose, rats were subjected to “standard”, “cafeteria” and “cafeteria diet + GSPE” treatments (n = 4/group) for 9 weeks (the last 4 weeks, GSPE/vehicle) of treatment, administering the extract/vehicle at diurnal or nocturnal times (ZT0 or ZT12). For circadian assessment, one hour after turning the light on (ZT1), animals were sacrificed every 6 h (ZT1, ZT7, ZT13 and ZT19). Interestingly, GSPE was able to restore the rhythm on clock hepatic genes (Bmal1, Per2, Cry1, Rorα), as this correction was more evident in nocturnal treatment. Additionally, during nocturnal treatment, an increase in hepatic fusion genes and a decrease in fission genes were observed. Regarding mitochondrial complex activity, there was a strong effect of cafeteria diet at nearly all ZTs, and GSPE was able to restore activity at discrete ZTs, mainly in the diurnal treatment (ZT0). Furthermore, a differential behavior was observed in tricarboxylic acid (TCA) metabolites between GSPE diurnal and nocturnal administration times. Therefore, GSPE may serve as a nutritional preventive strategy in the recovery of hepatic-related metabolic disease by modulating mitochondrial dynamics, which is concomitant to the restoration of the hepatic circadian machinery.
Highlights
The typical role of mitochondria is oxidative phosphorylation, which provides adenosine triphosphate (ATP) as a primary energy source for most biochemical and physiological processes
Animals treated with grape-seed procyanidin extract (GSPE) at night (ZT12) showed a reduction in bodyweight gain when compared to the control cafeteria diet (CAF)-fed group (p = 0.005)
Globally, this result is in agreement with previous studies that showed GSPE efficiency for treating metabolic syndrome and, body weight [47–49]
Summary
The typical role of mitochondria is oxidative phosphorylation, which provides adenosine triphosphate (ATP) as a primary energy source for most biochemical and physiological processes These intracellular double-membrane-bound structures play a pivotal role in ion homeostasis, apoptosis, reactive oxygen species (ROS) production, and in several metabolic pathways since they host fatty acid β-oxidation, as well as urea and. These organelles were originally considered static cellular powerhouses, it is known that they connect and exchange materials with other cellular organelles, including the nucleus and the endoplasmic reticulum [3,4]. In this sense, mitochondrial organelles are seen as dynamic structures that actively “evolve” in response to the energy demand and supply. Mitochondrial fission is related to a decrease in ATP production, an increase in mitochondrial uncoupling and nutrient storage to avoid waste of energy and the deleterious effect of food excess [7]
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