Orexin activation precedes increased NPY expression, hyperphagia, and metabolic changes in response to sleep deprivation.

Several pieces of evidence support that sleep duration plays a role in body weight control. Nevertheless, it has been assumed that, after the identification of orexins (hypocretins), the molecular basis of the interaction between sleep and energy homeostasis has been provided. However, no study has verified the relationship between neuropeptide Y (NPY) and orexin changes during hyperphagia induced by sleep deprivation. In the current study we aimed to establish the time course of changes in metabolite, endocrine, and hypothalamic neuropeptide expression of Wistar rats sleep deprived by the platform method for a distinct period (from 24 to 96 h) or sleep restricted for 21 days (SR-21d). Despite changes in the stress hormones, we found no changes in food intake and body weight in the SR-21d group. However, sleep-deprived rats had a 25-35% increase in their food intake from 72 h accompanied by slight weight loss. Such changes were associated with increased hypothalamus mRNA levels of prepro-orexin (PPO) at 24 h followed by NPY at 48 h of sleep deprivation. Conversely, sleep recovery reduced the expression of both PPO and NPY, which rapidly brought the animals to a hypophagic condition. Our data also support that sleep deprivation rapidly increases energy expenditure and therefore leads to a negative energy balance and a reduction in liver glycogen and serum triacylglycerol levels despite the hyperphagia. Interestingly, such changes were associated with increased serum levels of glucagon, corticosterone, and norepinephrine, but no effects on leptin, insulin, or ghrelin were observed. In conclusion, orexin activation accounts for the myriad changes induced by sleep deprivation, especially the hyperphagia induced under stress and a negative energy balance.

Physiological variation in plasma total homocysteine concentrations in rats.

Hyperhomocysteinemia was initially related to cardiovascular diseases; but homocysteine (Hcy) metabolism disturbances have more recently associated with a wide range of pathophysiological conditions including age-related diseases, disrupted circadian rhythms and gynaecological disorders. Since in many cases we do not know to what extent animal models are physiologically similar to human ones, this study aimed to track spontaneous variations in rat plasma Hcy concentrations during different physiological processes such as life cycle, 24 hours and estrous cycle. Plasma total Hcy concentrations were accessed by HPLC. Plasma Hcy concentration varied with age and newborns had the lowest values (2.94 +/- 0.47 micromol/L). Rats aged 10 days presented concentration similar to 3 month old animals (6.87 +/- 0.67 and 8.29 +/- 1.55 micromol/L respectively). Values decreased to 6.42 +/- 1.65 micromol/L at 6 months and 4.87 +/- 0.81 micromol/L at 28 months. Concerning circadian variations in Hcy concentration cosinor analysis showed acrophase in young rats at 1:09 pm, but no plasma Hcy circadian variations in aged rats. Female rats showed changes in Hcy concentration during the estrous cycle with higher values during the diestrous I (10.61 +/- 1.81 micromol/L) compared with the estrous (8.47 +/- 1.86 micromol/L) and diestrous II (7.68 +/- 1.58 micromol/L) phases. In conclusion, plasma Hcy concentration varied spontaneously with ontogenic development and during the estrous cycle and presented a circadian rhythm variation in young rats.