Adropin is a peptide encoded by the energy homeostasis-associated gene ENHO,^[1] which is highly conserved across mammals.^[2]

Adropin's biological role was first described in mice by a group led by Andrew Butler, as a protein hormone, secreted from the liver (hepatokine), in the context of obesity and energy homeostasis. They derived the name "Adropin" from the Latin "aduro" - to set fire to, and "pinguis" - fat.^[3] The hormone adropin is produced in places like the liver and brain, as well as peripheral tissues in the heart and gastrointestinal tract.^[4]

In animals, adropin has been shown to have a regulatory role in carbohydrate/lipid metabolism,^[5] as well as in endothelial function.^[6][7] Adropin expression in the liver is regulated by feeding status and macronutrient content,^[5] as well as by the biological clock.^[8] Liver adropin is upregulated by estrogen^[9] via ERa.^[10]

In humans, lower levels of circulating adropin are associated with several medical conditions including metabolic syndrome, obesity^[11] and inflammatory bowel disease.^[12]

The brain is the organ with the highest levels of adropin expression.^[13] In the brain, adropin has been shown to have a potential protective role role against neurological disease,^[14] including in the context of brain aging and cognitive function,^[15][16] as well as following acute ischemia.^[17]

The orphan G protein-coupled receptor GPR19, has been proposed as a receptor for adropin.^[18][19]

In the mouse ovary, adropin and GPR19 are strongly detected in the granulosa cells of large antral follicles and corpus luteum.^[20] An additional study suggests a role for adropin in the acceleration of pubertal development.^[21]

Structure and Synthesis

Adropin is a small protein composed of 76 amino acids, and it is produced primarily in the liver and the brain. The precursor of adropin is a larger protein called Energy Homeostasis-Associated (ENHO), and adropin is released through the cleavage of ENHO.^[1]

Receptors and targets

The specific receptors for adropin are not yet fully elucidated, and this is an area of active research. However, studies suggest that adropin might exert its effects by interacting with certain cell surface receptors.^[22]

Metabolic

One of the primary areas of interest regarding adropin is its role in metabolic regulation. Research indicates that adropin may play a crucial role in glucose and lipid metabolism. It has been associated with insulin sensitivity, suggesting a potential role in the regulation of blood sugar levels.^[23]

In animal studies, alterations in adropin levels have been linked to changes in energy expenditure and body weight. For example, some studies have shown that mice with elevated adropin levels tend to be more resistant to diet-induced obesity.^[24]

Cardiovascular effects

Adropin also appears to have cardiovascular effects. It has been implicated in the regulation of endothelial function, which is essential for maintaining blood vessel health. Dysfunction in endothelial cells can contribute to conditions such as atherosclerosis and hypertension. Some studies suggest that adropin may have a protective role in cardiovascular health by promoting the dilation of blood vessels and reducing oxidative stress.^[25]

Brain function

Adropin is produced in the brain, particularly in the hypothalamus.^[4] The hypothalamus is a crucial region for the regulation of various physiological processes, including metabolism and energy balance. The presence of adropin in the brain suggests that it may have additional roles in the central nervous system, although the specifics are still being explored.

Circadian rhythm

There is evidence to suggest that adropin levels exhibit a circadian rhythm, meaning they follow a natural 24-hour cycle.^[26] Circadian rhythms play a vital role in regulating various physiological processes, including sleep-wake cycles, hormone secretion, and metabolism.

Systemic sclerosis

Adropin is a repressor of fibroblast activation and is dysregulated in patients with Systemic sclerosis. Adropin showed antifibrotic activity in mouse models of skin and lung fibrosis as well as in human skin biopsies. Thus, adropin is a potential therapeutic target in tissue fibrosis.^[27]

Clinical Implications

Given its involvement in metabolic and cardiovascular processes, adropin has sparked interest as a potential biomarker and therapeutic target for conditions such as obesity, diabetes, and cardiovascular disease. However, much more research is needed to understand the precise mechanisms of adropin action and its potential applications in clinical settings.