Daily Patterns and Adaptation of the Ghrelin, Growth Hormone and Insulin‐Like Growth Factor‐1 System Under Daytime Food Synchronisation in Rats

Abstract

Daytime restricted feeding promotes the re-alignment of the food entrained oscillator (FEO). Endocrine cues which secretion is regulated by the transition of fasting and feeding cycles converge in the FEO. The present study aimed to investigate the ghrelin, growth hormone (GH) and insulin-like growth factor (IGF)-1 system because their release depends on rhythmic and nutritional factors, and the output from the system influences feeding and biochemical status. In a daily sampling approach, rats that were fed ad lib. were compared with rats on a reversed (daytime) and restricted feeding schedule by 3 weeks (dRF; food access for 2 h), also assessing the effect of acute fasting and refeeding. We undertook measurements of clock protein BMAL1 and performed somatometry of peripheral organs and determined the concentration of total, acylated and unacylated ghrelin, GH and IGF-1 in both serum and in its main synthesising organs. During dRF, BMAL1 expression was synchronised to mealtime in hypophysis and liver; rats exhibited acute hyperphagia, stomach distension with a slow emptying, a phase shift in liver mass towards the dark period and decrease in mass perigonadal white adipose tissue. Total ghrelin secretion during the 24-h period increased in the dRF group as a result of elevation of the unacylated form. By contrast, GH and IGF-1 serum concentration fell, with a modification of GH daily pattern after mealtime. In the dRF group, ghrelin content in the stomach and pituitary GH content decreased, whereas hepatic IGF-1 remained equal. The daily patterns and synthesis of these hormones had a rheostatic adaptation. The endocrine adaptive response elicited suggests that it may be associated with the regulation of metabolic, behavioural and physiological processes during the paradigm of daytime restricted feeding and associated FEO activity.

Voluntary exercise contributed to an amelioration of abnormal feeding behavior, locomotor activity and ghrelin production concomitantly with a weight reduction in high fat diet-induced obese rats

“…The degrees of obesity may have been different among studies, ranging from mild to genetically deficient severe obesity. The time points when plasma and tissue samples were collected might have affected the results regarding the ghrelin concentrations, because the plasma ghrelin concentration increases before meals and falls postprandially in humans [35], and a diurnal variation in the plasma ghrelin concentration was observed even in rats fed ad libitum, with a higher concentration observed during the light phase [36]. Finally, the handling of samples might have affected the results, because immediate centrifugation and the addition of hydrochloric acid to a retrieved plasma sample is essential to maintain the stability of this peptide until the assay is performed [24].…”

Daytime restricted feeding modifies the daily regulation of fatty acidβ-oxidation and the lipoprotein profile in rats

“…DRF promotes a phase shift in BMAL1 and PER1 (2,3) , an oxidised redox state in the mitochondria and cytosol (7) , higher levels of SIRT1 in hepatic cytosol before mealtime, and an elevated presence of cytosolic PGC-1α in the 24-h profile (14) . All these changes are associated with an enhanced 'fasting' response in DRF rats at times before food access (2,3,7,14) . In our results, the nucleus:cytosol ratio of SIRT1 exhibits a peak at the end of the dark phase ( Fig.…”

“…This new state in the circadian timing system allows the expression of an alternative circadian clock known as the food-entrained oscillator (FEO) (4,5) . The activity of the FEO involves a dynamic mutual interaction between the circadian molecular clock and the metabolic energy networks within a variety of tissues and organs (2)(3)(4)6) .…”

Restricted feeding modulates the daily variations of liver glutamate dehydrogenase activity, expression, and histological location

“…20 These novel metabolic and physiological outcomes are supported by two conceptual frameworks: a circadian entrainment that shifts the phase of the clock proteins and regulatory metabolic mechanism to mealtime, 31 and a hypocaloric condition that is implicit in the $30% lower food intake in the RF group. 32,33 It has been reported that three key regulatory parameters controlling liver metabolism are modified by the daytime restricted feeding schedule: redox state (becomes oxidized before food access), energy charge (ATP increases during food anticipatory activity), and mitochondrial activity (elevation of mitochondrial membrane potential) (in Mendoza 34 and references within). There are two ways to interpret the concept of FEO as a system to predict the availability of food: one is to consider the FEO as a variety of oscillators, responding to mealtime, located in the brain and periphery that act in coordination to modulate the behavioral, endocrine and metabolic responses when food-related cues alter the circadian timing system.…”