Anorexia is typically viewed as a pathological condition in humans, yet some animals naturally suppress food intake for extended periods without adverse consequences.
For ground squirrels, anorexia is not a pathological condition but an adaptive strategy for survival during hibernation.
A recent study published in Nature Communications investigated the hormonal mechanisms behind this reversible form of anorexia and identified pathways that may help researchers better understand appetite regulation and central hypothyroidism in humans.
Squirrels undergo distinct physiological states throughout the year.
| State | Characteristics |
|---|---|
| Active (Late spring to late summer) | High metabolism and increased food consumption |
| Pre-hibernation (Summer transition to fall) | Reduced food intake |
| Hibernation | 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 biological mechanisms behind hibernation-induced anorexia, researchers needed to accurately identify each physiological state.
Core body temperature was therefore a critical measurement throughout the study.
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.
Although hibernation is unique to certain mammals, many of the molecular pathways involved are also present in humans.
This makes ground squirrels a powerful translational model for studying the mechanism of central hypothyroidism and related human conditions.
The work also highlights the importance of long-term physiological monitoring technologies in uncovering mechanisms that cannot be observed through endpoint measurements alone.
