The FEO is expressed when animals have access to food on restricted schedules (2 to 4 h of mealtime per day over a period of 2 or 3 weeks). The restricted feeding schedule (RFS) increases locomotive activity and arousal during the hours immediately before food access, generating a condition known as food anticipatory activity (FAA) [9]. Ilomastat clinical trial FAA is characterized by a variety of physiological and behavioral changes in the organism such as: increases in wheel running activity, water consumption, and body temperature, as well as a peak of serum corticosterone [9–11]. So far, the anatomical location of the FEO is unknown,

but the physiology of this oscillator is thought to involve the bidirectional communication between specific, energy-sensitive brain areas and nutrient-handling, peripheral organs, especially the liver [8, 9, 11]. The liver is primarily composed of parenchymal cells or hepatocytes (80% by volume) and four types of non-parenchymal cells: endothelial, Kupffer, Ito, and pit cells. Hepatic tissue is highly specialized and functions

as a major effector organ, acting as: 1) principal center of Belnacasan cost nutrient metabolism, 2) major component of the organism defensive response, 3) control station of the endocrine system, and 4) blood reservoir [12]. The hepatic gland performs a strategic role in the digestive process by receiving the nutrients from the diet and AZD6738 orchestrating their transformation into useful biomolecules to be delivered to other organs and tissues. Hence, the liver is fundamental in the

metabolism of carbohydrates, lipids, and all other biomolecules. Hypothalamic and midbrain nuclei are connected via vagal and splanchnic nerves to the liver, allowing the hepatic organ to participate in the control of food intake by sensing and regulating the energy status of the body [13]. FEO expression promotes dramatic changes in the physiology and metabolic performance of the liver [11, 14, 15]: During the FAA (before food access), there is a prevalence of this website oxidized cytoplasmic and mitochondrial redox states, an increase in adenine nucleotides levels, an enhanced mitochondrial capacity to generate ATP, and a hypothyroidal-like condition that is not systemic but exclusively hepatic. In contrast, after feeding the hepatic redox state becomes reduced in both cytoplasmic and mitochondrial compartments, the levels of ATP decline, and the level of T3 within the liver increases. However, not all the adaptations in the liver during RFS occur before and after food intake. A constant reduction in pro-oxidant reactions (conjugated dienes and lipid peroxides) in most hepatocyte subcellular fractions and a persistent increase in the mitochondrial membrane potential (ΔΨ) are observed along FEO expression [14, 16]. In addition, the liver is the organ that displays the fastest shift in the phase of clock-control genes and molecular outputs in response to food access being restricted to daytime in nocturnal rodents [17].