There is a group of Harvard who has studied the role of the ventrolateral preoptic area (VLPO) in sleep, feeding, and autonomic processes in the hypothalamus for nearly two decades. The lab, led by Dr. Cliff Saper (aka Dr. VLPO), is most famous for discovering that the VLPO is a sleep-promoting area with GABA-ergic and galanin (both inhibitory) projections to other hypothalamic areas. In a recent study published in SLEEP, the lab members used this knowledge to examine what effect a chronic reduction in spontaneous amounts of sleep and wakefulness had on physiological markers of metabolic syndrome; increased body ResearchBlogging.orgweight, reduced insulin sensitivity, and adiposity. Most short- and long-term sleep deprivation protocols involve mild stress and loss of thermoregulation because the animal is forced to stay awake by means of gentle handling, placement on a slow-moving, fun house-like wheel, or water immersion. This study, however, removed these experimental confounds by lesioning the VLPO which results in a 40% irreversible reduction in daily sleep amounts and more importantly, this loss of sleep is intermittent which more often models human sleeping habits. Although not expected, rats with VLPO lesions were “healthier” animals. They were less resistant to gain weight across the 60 days of experimentation, and further, they had lower levels of plasma triglycerides and glucose even though they were eating the same amount of food as control rats. With respect to sleep, there was a direct linear relationship between the number of neurons destroyed in the VLPO by the chemical (saporin) injection and the percent of wakefulness and general locomotor activity across 24 hr. These measures also correlated with a resistance to weight gain. Thus, although hyperactivity partially explains these healthier physiological profiles despite an inbalance in daily sleep amounts, we cannot forget that there were changes in ghrelin and leptin levels too, which are largely under central control; as a reminder, ghrelin encourages feeding, while leptin curtails it. In the VLPO-lesioned rats, levels of ghrelin increased while those of leptin decreased, but yet this endocrine change did not alter daily levels of food intake! This unique finding is a platform for future studies. On a larger level, this study indicates that some of the reported contributions of sleep loss to metabolic syndrome may be due to circadian misalignment. A majority of sleep deprivation protocols begin at lights-on which in humans, would be comparable to staying up to 4 am on a weekend night. And we all know how long it takes to recover and what happens to one’s diet and lifestyle from that…..

Vetrivelan R, Fuller PM, Yokota S, Lu J, & Saper CB (2012). Metabolic effects of chronic sleep restriction in rats. Sleep, 35 (11), 1511-20 PMID: 23115400