Anorexia, a condition characterized by a significant reduction in food intake despite negative energy balance, poses severe risks to health and quality of life. It manifests in various forms in humans, including anorexia nervosa and physiological anorexia. While psychological and social factors have been widely studied, the physiological causes remain less understood.
For ground squirrels, anorexia is not a pathological condition but an adaptive strategy for survival during hibernation. Recent research by Sarah M. Mohr et al highlights the unique hibernation patterns of thirteen-lined ground squirrels, which could provide valuable insights into anorexia in humans.
Squirrels undergo distinct physiological states throughout the year. In the active state, which spans late spring to late summer, they have high metabolism and increased food consumption. As summer transitions to fall, they enter a pre-hibernation phase where food intake decreases. During the hibernation period itself, these squirrels experience cycles of torpor characterized by dramatically reduced metabolic activity, interspersed with 24–48-h periods of an active-like interbout arousal (IBA) state.
To understand the mechanism underlying this remarkable example of reversible anorexia, thirteen-lined ground squirrels (Ictidomys tridecemlineatus) were studied during the active and the hibernation seasons.
Core body temperature was monitored, using an easyTEL + implant that was specially adapted to this unusual temperatures range, from 4 to 40°C. “Active” squirrels maintained a stable core body temperature of 37 °C. “Pre-hibernation” squirrels generally maintained euthermia, but occasionally experienced transient hypothermia, dropping to around 20°C. “IBA” squirrels had undergone at least one episode of hypothermic torpor during hibernation but had reached a core body temperature above 32°C for at least 60 minutes, or above 20°C for a minimum of 20 minutes.
The study revealed that hibernating ground squirrels consume six times less food than they do during active seasons. This hibernation-related anorexia is linked to a deficiency of the triiodothyronine (T3) hormone in the hypothalamus during hibernation. Thyroid hormones are vital in regulating feeding behavior, and experiments where T3 was infused directly into the hypothalamus of hibernating squirrels confirmed its pivotal role in restoring appetite.
Squirrels also exhibit decreased levels of serum glucose and insulin, along with increased levels of β-hydroxybutyrate, signaling a metabolic shift toward fat utilization.
Interestingly, while levels of ghrelin, an appetite-stimulating hormone, remain unchanged, the squirrels develop resistance to its effects during hibernation. Similarly, leptin, another key hormone involved in regulating satiety, shows reduced signaling during hibernation.
Moreover, the study suggests that this seasonal anorexia is linked to decreased expression of monocarboxylate transporter 8 (MCT8), which is a Thyroid hormone transporter. There are also alterations in the expression of immunoglobulin superfamily member 1 (IGSF1), a protein associated with central hypothyroidism.
Unlike humans, central hypothyroidism as a vital aspect of squirrels physiology. However, this process relies on similar molecular pathways, suggesting hibernating squirrels as a relevant model to study the mechanism of central hypothyroidism and related human conditions.
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