Anticipatory changes in liver metabolism and entrainment of insulin, glucagon, and corticosterone in food-restricted rats

Abstract

Restricted feeding schedules entrain behavioral and physiological circadian rhythms, which depend on a food-entrainable oscillator (FEO). The mechanism of the FEO might depend on digestive and endocrine processes regulating energy balance. The present study characterizes the dynamics of circulating corticosterone, insulin, and glucagon and regulatory parameters of liver metabolism in rats under restricted feeding schedules. With respect to ad libitum controls, food-restricted rats showed 1) an increase in corticosterone and glucagon and a decrease in insulin before food access, indicating a predominant catabolic state; and 2) a reduction in lactate-to-pyruvate and beta-hydroxybutyrate-to-acetoacetate ratios, indicating an oxidized cytoplasmic and mitochondrial redox state in the liver metabolism. All these changes were reversed after feeding. Moreover, liver energy charge in food-restricted rats did not show a significant modification before feeding, despite an increase in adenine nucleotides, but showed an important decrease after food intake. Variations detected in the liver of food-restricted rats are different from those prevailing under 24-h fasting. These observations suggest "anticipatory activity" of the liver metabolism to optimize the processing of nutrients to daily feeding. Data also suggest a possible relationship of the liver and endocrine signals with the FEO.

Liver 5'-deiodinase activity is modified in rats under restricted feeding schedules: evidence for post-translational regulation

“…These results are in agreement with previous reports showing that the AAs secondary to RFSs exhibit specific regulatory parameters of liver metabolism (Díaz-Muñoz et al 2000) and support the notion that the physiological state of rats under an RFS is unique and distinct from rats fed freely or fasted for 24 h (Persons et al 1993). Our results confirm previous data on fasting regimens showing that although changes in systemic thyroid status are evident until 48 or 72 h after fasting, liver D1 activity and mRNA content start to decrease within 24 h or less (Reimers et al 1986, O'Mara et al 1993, Kmiec et al 1996.…”

“…Moreover, the lack of signal in the long D1 mRNA amplification for all the samples is in agreement with previous work where we demonstrated that the large mRNA form was expressed only in metabolic overdemand situations like chronic hyperthyroidism, lactation or adrenergic stimulation (Aceves & Huidobro 2001), and it suggests that in normal or fasting regimens D1 enzyme is encoded by the short messenger. The low D1 activity measured before food presentation (0800 and 1100 h) was coincident with a significant increase in corticosterone serum levels (Díaz-Muñoz et al 2000), whereas the enhancement in D1 activity after feeding (1400 h) was concurrent with a peak in serum insulin (Díaz-Muñoz et al 2000). These correlations could be part of a possible mechanism to account for the changes in D1 activity in RFS rats, since Davies et al (1996) and Sato et al (1983) reported that hepatic D1 activity is decreased by glucocorticoid administration and stimulated by insulin treatment respectively.…”

“…Although the expression of timing mechanisms has been identified, little is known about the nature of the metabolic adaptations of the liver during RFSs. We have reported the entrainment of both metabolites of energetic significance and hormones such as insulin, glucagon and corticosterone in food-restricted rats (Escobar et al 1998, Díaz-Muñoz et al 2000. We also demonstrated significant changes in crucial parameters of liver metabolism such as the energetic charge (E c =YATP+ADP/ATP+ADP+ AMP) and the cytoplasmic and mitochondrial redox states (NAD+/NADH ratio), which were coincident with the onset of the AA (Díaz-Muñoz et al 2000).…”

“…Based on the hypothesis that FEO function involves a metabolic and/or neural communication between peripheral organs and selective brain areas (Stephan 2002), our group has shown that liver presents adaptations in two of the principal parameters that regulate intermediate metabolism, namely energy charge and redox state in foodrestricted rats (Díaz-Muñoz et al 2000). In the present study, we examined the effect of food restriction and a 24 h fast on thyroid economy, one of the most influential endocrine factor in the hepatic metabolic status (Feng et al 2000, Flores-Morales et al 2002.…”

“…We have reported the entrainment of both metabolites of energetic significance and hormones such as insulin, glucagon and corticosterone in food-restricted rats (Escobar et al 1998, Díaz-Muñoz et al 2000. We also demonstrated significant changes in crucial parameters of liver metabolism such as the energetic charge (E c =YATP+ADP/ATP+ADP+ AMP) and the cytoplasmic and mitochondrial redox states (NAD+/NADH ratio), which were coincident with the onset of the AA (Díaz-Muñoz et al 2000). It has been reported that dexamethasone resets clock gene rhythmicity in the liver and other peripheral tissues but not in the SCN, and induces rhythmic fluctuations in clock genes when applied to fibroblasts maintained in culture (Balsalobre et al 2000).…”