The resistin , also known as specific secretory factor adipose tissue (ADSF for short English), is a peptide hormone rich in cysteine. Its name is due to the positive correlation (resistance) it presents to the action of insulin. It is a cytokine that has 10 to 11 cysteine residues.
It was discovered in 2001 in adipositic cells (adipose tissue) of mice and in immune and epithelial cells of humans, dogs, pigs, rats and various species of primates.
The role of this hormone has been highly controversial since its discovery, due to its involvement in the physiology of diabetes and obesity. It is also known to have other medical implications, such as an increase in bad cholesterol and low-density lipoproteins in the arteries.
Resistin is part of a family of resistin-type molecules (Resistin like molecules, RELMs). All members of the RELMs family present an N-terminal sequence, which presents the secretion signal that is between 28 and 44 residues.
They have a variable central region or zone, with a carboxyl terminal end, of a domain that varies between 57 and about 60 residues, highly preserved or conserved and abundant in cysteine.
This protein has been found in several mammals. Most attention has been directed to resistin secreted by mice and present in humans. These two proteins show 53 to 60% similarity (homologies) in their amino acid sequences.
In these mammals, the main source of resistin is adipose cells or white adipose tissue.
Resistin in mice is rich in 11 kDa cysteine. The gene for this protein is located on the eighth (8) chromosome. It is synthesized as a 114 amino acid precursor. They also have a 20 amino acid signal sequence and a 94 amino acid mature segment.
Structurally resistin in mice has five disulfide bonds and multiple β turns. It can form complexes of two identical molecules (homodimers) or form proteins with quaternary structures (multimers) of different sizes thanks to the disulfide and non-disulfide bonds.
Human resistin is characterized by being, as in mice or other animals, a peptide protein rich in cysteine, only in humans it is 12 kDa, with a mature sequence of 112 amino acids.
The gene for this protein is found on chromosome 19. The source of resistin in humans is macrophage cells (cells of the immune system) and epithelial tissue. It circulates in the blood as a dimeric protein of 92 amino acids linked by disulfide bonds.
Resistin is known by multiple names, including: cysteine-rich secreted protein FIZZ3 (Cysteine-rich secreted protein FIZZ3), adipose tissue-specific secretory factor (ADSF), adipose tissue-specific secretory factor (ADSF), protein rich in C / EBP-epsilon-regulated myeloid-specific secreted cysteine-rich protein, secreted cysteine-rich protein A12-alpha-like 2 (Cysteine-rich secreted protein A12- alpha-like 2), RSTN, XCP1, RETN1, MGC126603 and MGC126609.
This protein is relatively new to the scientific community. It was discovered independently by three groups of scientists at the beginning of this century, who gave it different names: FIZZ3, ADSF, and resistin.
It was discovered in 2000, in inflamed lung tissue. Three genes from mice and two homologous genes from humans associated with the production of this protein were identified and described.
Protein discovered in 2001, thanks to the identification of a secretion factor rich in cystine (Ser / Cys) (ADSF) specific to white lipid tissue (adiposites).
This protein was assigned an important role in the process of differentiation from multiple cells to mature adiposites (adipogenesis).
Also in 2001, a group of researchers described the same protein rich in cystine in the mature lipid tissue of mice, which they called resistin because of its resistance to insulin.
Structurally, it is known that this protein is made up of a laminar-shaped front area or head, and a helical-shaped rear area (tail), forming oligomers of different molecular weights, depending on whether it is human or of another origin.
It has a central region with 11 Ser / Cys (Serine / Cysteine) residues and an area also rich in Ser / Cys whose sequence is CX11CX8CXCX3CX10CXCXCX9CCX3-6, where C is Ser / Cys and X is any amino acid.
It has a structural composition considered unusual, since it is formed by several subunits joined by non-covalent interactions, that is, they do not use electrons, but dispersed electromagnetic variations to make up their structure.
The functions of resistin, to date, are the subject of extensive scientific debate. Among the most relevant findings of the biological effects in humans and mice are:
- Multiple tissues in humans and mice react to resistin, including liver, muscle, heart, immune, and fat cells.
- Hyperresistinemic mice (that is, with elevated levels of resistin) experience impaired glucose self-regulation (homeostasis).
- Resistin decreases insulin-stimulated glucose uptake in heart muscle cells.
- In immune cells (macrophages) in humans, resistin induces the production of proteins that coordinate the response of the immune system (inflammatory cytokines)
In humans, this protein is thought to contribute physiologically to insulin resistance in diabetes mellitus.
The role it plays in obesity is still unknown, although it has been found that there is a correlation between increased adipose tissue and resistin levels, that is, obesity increases the concentration of resistin in the body. It has also been shown to be responsible for high levels of bad cholesterol in the blood.
Resistin modulates molecular pathways in inflammatory and autoimmune pathologies. It directly causes the functional alteration of the endothelium, which in turn leads to hardening of the arteries also known as atherosclerosis.
Resistin works as an indicator of diseases and even as a predictive clinical tool for cardiovascular diseases. It is involved in the production of blood vessels (angiogenesis), thrombosis, asthma, nonalcoholic fatty liver disease, chronic kidney disease, among others.
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