Circadian and Ultradian Variations of Leptin in Normal Man under Continuous Enteral Nutrition: Relationship to Sleep and Body Temperature

Abstract

To determine the influence of circadian rhythmicity and sleep on the 24-h leptin diurnal variations, plasma leptin levels were measured at 10-min intervals over 24 h in seven normal subjects, once during nocturnal sleep, and once after an 8-h shift of sleep. The subjects were submitted to constant conditions (continuous enteral nutrition and bed rest in controlled chambers). Body temperature and plasma glucose and insulin levels were measured simultaneously. During nighttime sleep, leptin levels increased to a maximum (109.9 +/- 2.5% of the 24-h mean) and then decreased to reach a nadir in the late afternoon. The mean diurnal variation was 18.0 +/- 3.8% of the 24-h mean. In the daytime sleep condition, leptin levels rose during the night of deprivation to a maximum of 104.7 +/- 2.3% of the 24-h mean, decreased to a minimum around 0700 h, and then rose again during diurnal sleep (108.4 +/- 3.1% of the 24-h mean); the mean diurnal variation was 13.4 +/- 3.6% of the 24-h mean. ANOVA revealed a significant interaction between time of day and sleep effects (P < 0.05). The diurnal and the sleep-related variations of plasma leptin mirrored those of body temperature and roughly paralleled those of plasma glucose and insulin; the amplitudes of the diurnal leptin variations were significantly correlated with the amplitudes of the diurnal body temperature variations (P < 0.05). Plasma leptin levels also displayed irregular pulses of low amplitude (mean duration, 70 min) that were not affected by sleep, but were associated with a significant decrease in glucose and insulin levels (P < 0.01). These results demonstrate that under continuous enteral nutrition, plasma leptin levels are modulated by both a slight circadian component and sleep, which interact under normal conditions, and suggest that leptin is implicated in circadian thermoregulatory adjustments.

Clock genes and sleep

“…Under un-stressed and constant feeding conditions, leptin shows a marked nocturnal rise in humans [128]. When sleeping time is shifted by 8 h, leptin levels are differentially regulated by both the circadian system and sleep, resulting in a short period rhythm with peaks in the night and around mid-sleep phase [136]. In contrast, the diurnal expression of ghrelin seems not to be directly clock-regulated.…”

Functional architecture of behavioural thermoregulation

“…Indeed, it has been known for some time that the dorsomedial hypothalamus is involved in chemical signals related to food consumption and ingestive behaviour both of which represent hypothalamic functions linked with thermoregulation (Hamilton and Ciaccia 1971). For instance, leptin, a peptide involved in feeding behaviour, raises body temperature in mice and rats (Stehling et al 1997) and is implicated in the human behavioural, autonomic, and endocrine control of nycthemeral body temperature rhythm (Simon et al 1998). Administration of two other peptides, vasopressin and oxytocin, through intracerebroventricular injection induces grooming behaviour, characteristic of heat loss (Drago et al 1997).…”

Sueño y sistema inmune

“…60 Aunado a esto aumenta la liberación de leptina por los adipocitos para evitar la sensación de hambre durante el sueño. 61 El eje HPA incrementa su actividad durante la última parte del sueño nocturno y prepara al orga-nismo para la actividad diaria. Así, el cortisol y las catecolaminas, que generalmente suprimen la función inmune, aumentan por la mañana, con lo cual se apaga la respuesta proinfl amatoria evocada durante la noche 62 (Figura 1).…”