Adropin is a

protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residue (biochemistry), residues. Proteins perform a vast array of functions within organisms, including Enzyme catalysis, catalysing metab ...

encoded by the energy homeostasis-associated

gene In biology, the word gene has two meanings. The Mendelian gene is a basic unit of heredity. The molecular gene is a sequence of nucleotides in DNA that is transcribed to produce a functional RNA. There are two types of molecular genes: protei ...

ENHO in humans and is highly conserved across mammals. The biological role of adropin was first described in mice by Andrew Butler's team. They identified it as a protein hormone (

hepatokine Hepatokines (Greek ''heapto-'', liver; and ''-kinos'', movement) are proteins produced by liver cells (hepatocytes) that are Secretion, secreted into the Circulatory system, circulation and function as hormones across the organism. Research is most ...

) secreted from the liver, playing a role in

obesity Obesity is a medical condition, considered by multiple organizations to be a disease, in which excess Adipose tissue, body fat has accumulated to such an extent that it can potentially have negative effects on health. People are classifi ...

and energy homeostasis. The name "Adropin" is derived from the Latin words " aduro" (to set fire to) and " pinguis" (fat). Adropin is produced in various tissues, including the liver, brain, heart, and gastrointestinal tract. In animals, adropin regulates carbohydrate and lipid metabolism and influences endothelial function. Its expression in the liver is controlled by feeding status, macronutrient content, as well as by the biological clock. Liver adropin is upregulated by

estrogen Estrogen (also spelled oestrogen in British English; see spelling differences) is a category of sex hormone responsible for the development and regulation of the female reproductive system and secondary sex characteristics. There are three ...

via the

estrogen receptor alpha Estrogen receptor alpha (ERα), also known as NR3A1 (nuclear receptor subfamily 3, group A, member 1), is one of two main types of estrogen receptor, a nuclear receptor (mainly found as a chromatin-binding protein) that is activated by the sex ...

(ERα). In humans, lower levels of circulating adropin are linked to several medical conditions, including the

metabolic syndrome Metabolic syndrome is a clustering of at least three of the following five medical conditions: abdominal obesity, high blood pressure, high blood sugar, high serum triglycerides, and low serum high-density lipoprotein (HDL). Metabolic syndro ...

, obesity, and

inflammatory bowel disease Inflammatory bowel disease (IBD) is a group of inflammatory conditions of the colon and small intestine, with Crohn's disease and ulcerative colitis (UC) being the principal types. Crohn's disease affects the small intestine and large intestine ...

. and

. The brain exhibits the highest levels of adropin expression, In the brain, adropin has been shown to have a potential protective role against neurological disease, where it may play a protective role against neurological diseases, brain aging, cognitive decline, and acute

ischemia Ischemia or ischaemia is a restriction in blood supply to any tissue, muscle group, or organ of the body, causing a shortage of oxygen that is needed for cellular metabolism (to keep tissue alive). Ischemia is generally caused by problems ...

. as well as following acute

. The orphan G protein-coupled receptor GPR19 has been proposed as a receptor for adropin.

Structure

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.

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.

Function

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. 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. A study in humans demonstrated that changes in vascular

insulin resistance Insulin resistance (IR) is a pathological response in which cells in insulin-sensitive tissues in the body fail to respond normally to the hormone insulin or downregulate insulin receptors in response to hyperinsulinemia. Insulin is a horm ...

following short-term adverse lifestyle changes were associated with a decrease in plasma adropin in men but not women, perhaps related to adropin's regulation by estrogen.

Cardiovascular

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. In mice, adropin regulates cardiac energy metabolism and improves cardiac function and efficiency. In rats, adropin treatment alleviated diabetes related myocardial fibrosis and

diastolic dysfunction Heart failure with preserved ejection fraction (HFpEF) is a form of heart failure in which the ejection fraction – the percentage of the volume of blood ejected from the left ventricle with each heartbeat divided by the volume of blood when the ...

, and enhanced the therapeutic potential of

mesenchymal stem cells Mesenchymal stem cells (MSCs), also known as mesenchymal stromal cells or medicinal signaling cells, are multipotent stromal cells that can differentiate into a variety of cell types, including osteoblasts (bone cells), chondrocytes (cartilage ...

myocardial infarction A myocardial infarction (MI), commonly known as a heart attack, occurs when Ischemia, blood flow decreases or stops in one of the coronary arteries of the heart, causing infarction (tissue death) to the heart muscle. The most common symptom ...

Central nervous system

Adropin is produced in the brain, particularly in the hypothalamus. 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. Circadian rhythms play a vital role in regulating various physiological processes, including sleep-wake cycles, hormone secretion, and metabolism.

Gonads and sexual development

In mice, adropin treatment significantly increased

sperm count A semen analysis (plural: semen analyses), also called seminogram or spermiogram, evaluates certain characteristics of a male's semen and the sperm contained therein. It is done to help evaluate male fertility, whether for those seeking pregnancy ...

and testicular testosterone by increasing expression of GPR19 and steroidogenic proteins via modulating redox potential. In the mouse

ovary The ovary () is a gonad in the female reproductive system that produces ova; when released, an ovum travels through the fallopian tube/ oviduct into the uterus. There is an ovary on the left and the right side of the body. The ovaries are end ...

, adropin and GPR19 are strongly detected in the granulosa cells of large antral follicles and corpus luteum. An additional study suggests a role for adropin in the acceleration of pubertal development.

Clinical significance

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.

Systemic sclerosis

Adropin is a repressor of

fibroblast A fibroblast is a type of cell (biology), biological cell typically with a spindle shape that synthesizes the extracellular matrix and collagen, produces the structural framework (Stroma (tissue), stroma) for animal Tissue (biology), tissues, and ...

activation and is dysregulated in patients with

Systemic sclerosis Systemic scleroderma, or systemic sclerosis, is an autoimmune rheumatic disease characterised by excessive production and accumulation of collagen, called fibrosis, in the skin and internal organs and by injuries to small arteries. There are tw ...

. 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.