All glycogen aggregates disappeared after 24 h of fasting, with no further alteration in the structure of the other organelles (Panel B and E). In contrast, hepatocytes from rats during the FAA showed remarkable changes, including an increased opacity that made the cristae

difficult to distinguish. Some glycogen was also observed in these hepatocytes, supporting the result obtained with the PAS stain (panels C and F). Figure 8 Electron micrographs illustrating liver cells from control (A and D) fasten Selleck EPZ 6438 (B and D) and fed restricted (C and E) rats. Notice that hepatocytes from the fed restricted animal (F) exhibit electron-dense mitochondria (m) surrounded by abundant smooth endoplasmic reticulum (SER). N = cell nucleus,

gl = glycogen, asterisks Birinapant = lipid droplets, arrows = bile canaliculi. Lead-uranium staining. Scale bars = 2 μm in A-C; 0.2 μm in D-E. Representative images of 6 independent experimental observations. Discussion The liver is the principal organ that processes nutrients and delivers metabolites to peripheral tissues and organs; hence, it plays a key role in regulating the energy balance of vertebrates and thereby is fundamental in the physiological control of the hunger-satiety cycle [23]. Because feeding determines the individual viability, the timing of the underlying internal metabolic and cellular mechanisms to find and ingest food is properly regulated by circadian systems [24]. In consequence, a variety of liver

functions related to the handling of nutrients are targets of circadian control [25]. For these reasons, the hepatic involvement has been considered as an important constituent of the FEO [8, 11, 17]. Indeed, the FEO expression also depends on the nutritional properties and the caloric content of the meal nearly offered during the RFS [26]. Many of the adaptations in the biochemical responses of the liver before and after feeding during the FEO expression are unique, and do not correspond to the characteristics shown in either control group: fed ad libitum or 24-h fasting [10, 11, 14–16]. Taken together, the data strongly suggest that FEO physiology is associated with a new rheostatic equilibrium in the functional and structural properties of the liver that adapt to optimizing the handling of nutrients under the RSF status [11, 15, 27]. The liver exhibits daily fluctuations in structural and metabolic features, usually associated with the intake and processing of nutrients from the diet. This oscillatory pattern involves daily adjustments in the hepatocyte function to achieve a suitable assimilation of food, and then a correct processing of nutrients [28]. RFS leads to a striking hyperphagia that result in the ingestion of ≈ 30 g of food during the mealtime. By the time the stomach is almost empty, the FAA begins [29].