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Revision as of 16:31, 7 January 2025 by LDN007 (talk | contribs) (For a new gene and promising drug)(diff) ← Previous revision | Latest revision (diff) | Newer revision → (diff)Basic information
Breg, also named ADISSP, is a 19kd small polypeptide and an adipokine; it was discovered and named by Qingbo Chen, Yongxu Wang, and published with the name "Breg" on bioRxiv first, on August 16, 2022. And finally published online with the name ADISSP on December 10, 2022, on the magazine"Nature Communications". Under normal basal condition (without any external stimuli), it is largely secreted by the brown fat cell; and in turn activate thermogenic function in brown fat cell. In mouse, Breg can efficiently decrease blood glucose and combat obesity. It’s a thermogenic molecule that initiate thermogenesis programs in brown adipose tissue (BAT) and promote browning in inguinal white adipose tissue (iWAT). Human adults with low level Breg are obese.
In mouse, Breg is mainly expressed in the classic inter-scapular BAT, followed in the iWAT, and with lowest expression in the epididymal white adipose tissue (eWAT). Most importantly, under basal culture condition, without any external stimuli, Adissp is automatically largely secreted, at least, by the brown fat cell, and it activates thermogenic function; it means that both the secretion and function of Breg are in a cell-autonomous way. Breg is essential for both β3-Adrenergic receptor agonist, CL316,243 (CL), and acute cold to normally activate thermogenic programs. Breg systemically maintain energy homeostasis even under warm conditions. It is needed in cold, normal and warm temperature conditions.
The human homozygous of Breg is C20orf27; in 2020, it was reported that human Breg can promote cell growth and proliferation of colorectal cancer via the TGFβR-TAK1-NFĸB pathway.
Excellent Features (traits)
1), High-fat diet fed for 20 weeks, Breg Transgenic mice reduced about 66.5% diet-induced obesity (DIO); without any changes to food intake.
2), Breg robustly promote glucose uptake, primary and specifically, in the iWAT; and burning it as heat. Comparing to combat obesity, the function of Breg to reduce blood glucose is priority, especially when Breg level is not high enough. It's very different with insulin. And it means that Breg decreases blood glucose in an insulin independent ways.
3), the secretion of Breg is largely induced by CL in brown fat cell; this point out that Breg as a secondary signal regulator, it could overcome the side effects of β-Adrenergic receptors agonists in the cardiovascular system. Especially combine treatment with Breg+CL can increase UCP1 mRNA level 2 fold than CL treatment alone.
4), as Breg can be secreted into the circulation system, and largely induce thermogenesis, it means we can use it to re-built BAT function at least partially.
Therapy and safety
Body weight
Physiologically, fat tissues specifically loss or over-expression of Adissp can't result any body weight changes under both normal diet and high fat diet conditions. However, over-expression Adissp can remarkably combat obesity when mice fed on a high fat diet for a long time; and vice versa.
Naive and safe
Breg can exert its thermogenic function independent of both central nervous system and sympathetic nervous system, beyond of this, it can activate beneficial function independent of any external stimuli too. More, the secretion of Breg is largely induced by CL; and thermogenic function of Breg is independent of β-Adrenergic receptor signal pathways. It means that Breg is a downstream effector of CL, it can do what CL dose for thermogenesis, and meanwhile with low or no side effects of CL to non-fat tissues.
Commercial Availability
Circulation elevated Breg level by Adenovirus or AAV8 target delivery to liver tissue, or by tail vein deliver the purified Breg protein; both can maintain its function to facilitate thermogenesis and decrease blood glucose.
Based on the drug discovery failure lessons, Breg is a promising drug to bring benefit for the patients who are suffering obesity and obesity related disease. Hopefully, Breg would be an efficient drug to type two diabetes, just like what insulin does to type 1 diabetes.
Side Effects Prediction
Breg can largely reduce blood glucose, so super high Breg level could result in hypoglycemia. Besides, as an effects oof the β-Adrenergic receptor signal pathway, Breg could temporarily increase the fat acids level, especially at the early treatment stage.
Publications
1, Qingbo Chen et al. A brown fat-enriched adipokine Adissp controls adipose thermogenesis and glucose homeostasis. 2022, nature communications.
2, Qingbo Chen et al. A novel batokine Breg controls adipose thermogenesis and glucose homeostasis. 2022, bioRxiv.
3, Jing Gap et al. C20orf27 Promotes Cell Growth and Proliferation of Colorectal Cancer via the TGF R-TAK1-NFkB Pathway. 2020, cancers.
4, Breg Patent link: https://patents.google.com/patent/US11795201B2/en