Resistin
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| Location (UCSC) | Chr 19: 7.67 – 7.67 Mb | Chr 8: 3.71 – 3.71 Mb | |||||||
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Resistin also known as adipose tissue-specific secretory factor (ADSF) or C/EBP-epsilon-regulated myeloid-specific secreted cysteine-rich protein (XCP1) is a cysteine-rich peptide hormone derived from adipose tissue that in humans is encoded by the RETN gene.[5]
In
Discovery
Resistin was discovered in 2001 by the group of Dr
This idea primarily stems from studies demonstrating that
This article discusses the current research proposing to link resistin to inflammation and energy homeostasis, including its alleged role in insulin resistance in obese subjects, a subject reviewed by Vidal-Puig and O'Rahilly in 2001,[15] and by M.A. Lazar in 2007.[16]
Inflammation
Inflammation is the first
In further support of its inflammatory profile, resistin has been shown to increase transcriptional events, leading to an increased expression of several pro-inflammatory cytokines including (but not limited to)
In accordance, it is expected that, if resistin does serve as a link between obesity and T2DM while at the same time contributing to the inflammatory response, then proportional increases in
This adipokine is associated with markers of inflammation in seminal plasma and the concentrations of seminal resistin correlate positively with those of proinflammatory mediators such as interleukin-6 (IL-6), elastase and tumor necrosis factor-α (TNF-α). During inflammation, the concentrations of cytokines and ROS increase, and this may have a deleterious effect on the male reproductive function.[29] One study showed that there was a negative correlation between the concentrations of seminal resistin and spermatic motility and vitality. (The seminal concentrations of resistin were significantly higher in cases of leukocyte spermia or if the patients were smokers.)[30]
Obesity and insulin resistance
Arguments for
Much of what is
Although resistin levels increase with obesity, it is questioned whether this increase is responsible for the insulin resistance associated with increased adiposity.[citation needed] Several reports have shown a positive correlation between resistin levels and insulin resistance.[36][37][38][39] This is supported by reports of correlation between resistin levels and subjects with T2DM.[7][31][40][41] If resistin contributes to the pathogenesis of insulin resistance in T2DM, then designing drugs to promote decreased serum resistin in T2DM subjects may deliver therapeutic benefits.[42]
Resistin can increase levels of circulating
Arguments against
The amount of evidence supporting the resistin link theory between obesity and T2DM is vast.[citation needed] Nevertheless, this theory lacks support from the entire scientific community, as a number of studies present evidence against it.[44][45][46] Such studies have found significantly decreased serum concentrations of resistin with increased adiposity,[47][48][49] suggesting not only that resistin is downregulated in obese subjects, but also that decreased resistin levels may contribute to the links between obesity and T2DM. Data contradicting the idea that weight loss coincides with decreased serum resistin concentrations have also been presented; such studies instead report that weight loss is associated with marked increases in serum resistin.[21] The idea that resistin links obesity to T2DM is under scrutiny, reports have been made of ubiquitous resistin expression in many tissues, rather than only those characteristic of obesity, such as adipocytes [citation needed].
Although nearly as many scientists oppose the theory as those who support it [
Structure
| OPM superfamily | 384 | ||||||||
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| OPM protein | 1rgx | ||||||||
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Crystal structures of resistin reveal an unusual composition of several subunits that are held together by
The interchain disulfide bonds of resistin and resistin-like molecule β (RELMß) are novel in that they are highly solvent when exposed, ranging from 84.6% to 89.5%. An average solvent exposure for all disulfide bonds is 9.9%, and 16.7% for 1,209 interchain disulfide bonds. Therefore, the most highly uncovered disulfide bonds found for intact proteins are resistin's disulfides in high-resolution.
A Cys6Ser resistin mutant was substantially more potent at the low concentration and had a greater effect than the wild-type resistin at the high concentration. This result suggests that processing of the intertrimer disulfide bonds may reflect a mandatory step toward activation. Other results also suggest that both the Cys6Ser-mutant and wild-type resistin target mainly the liver.
References
- ^ a b c GRCh38: Ensembl release 89: ENSG00000104918 – Ensembl, May 2017
- ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000012705 – Ensembl, May 2017
- ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- PMID 12050208.
- PMID 17952831.
- ^ S2CID 4358808.
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- ^ PMID 15229336.
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- PMID 17952831.
- PMID 10921885.
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- ^ PMID 12429872.
- S2CID 29273978.
- PMID 12874180.
- S2CID 45491974.
- PMID 15864338.
- PMID 15033490.
- PMID 10961870.
- PMID 16395259.
- PMID 29971101.
- PMID 31772701.
- ^ PMID 14962997.
- S2CID 20609673.
- PMID 15045687.
- PMID 11994397.
- PMID 14768774.
- S2CID 1659156.
- PMID 15220189.
- PMID 14514348.
- PMID 12829623.
- PMID 14687894.
- PMID 14671216.
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- ^ "Canadian scientists discover cause of high cholesterol". Science Codex. October 28, 2012.
- PMID 12507502.
- PMID 14557464.
- PMID 11444881.
- PMID 15070954.
- PMID 11574398.
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External links
- Resistin at the U.S. National Library of Medicine Medical Subject Headings (MeSH)