Terbutaline Builds Muscle Without ß-oxidation

[LeeLemonoil]

β2-Agonists Build Muscle: Low Dose Terbutaline Adds 1kg (DXA) in 4 Weeks - With and Without Resistance Training - SuppVersity: Nutrition and Exercise Science for Everyone

 

[vulture]

Looks too good to be true...

 

[managing]

what would the downside/side effects of beta2 inhibition be?

What other substances are known to be beta2 antagonists?

 

[Terma]

This is getting crazy. The orphan receptor (NOR1) they're talking about on The Myostatin <> Clenbuterol Connection - More Muscle, Less Fat: Is an Orphan Nuclear Receptor the Missing Link? - SuppVersity: Nutrition and Exercise Science for Everyone and Myostatin (affects MyoD) are related to the UCP gene expression that @Travis was just digging into in the Vitamin D thread.

Zhang et al. emphasize that these fat-burning effects, of which further analyses revealed that they are mediated largely by "enhanced PPAR pathway signalling" and increased expression of mitochondrial uncoupling proteins (>4x PPAR-a; >12x UCP1, >6x UCP2 and >4x UCP3 in epididymal white adipose tissue of HFD myostatin-negative mice)

The only thing I can point out at this time is the recurring associations between PPAR and UCP. I think the only possible situation where they wouldn't associate would be during a simultaneous high carbohydrate intake, but that's just speculation, they could even be genetically programmed regardless of it. I'm way too tired to absorb all this.

 

[Terma]

I would indeed be very cautious about the main article you linked to because the source article (https://onlinelibrary.wiley.com/doi/abs/10.1111/sms.13221) is extremely low on useful information. They don't even bother to speculate. It appears made purely to motivate an anti-doping regulation against the drug.

If I had to purely guess, it would be that terbutaline increases PPARgamma in muscle, for whatever reason.

 

[Terma]

Here we go (I'm gonna do the bolding thing like the other posters... the above wasn't me, it was copy-pasted from the article; I didn't even know it would preserve the HTML markup formatting - I'm impressed by the forum software):
PPARγ and MyoD are differentially regulated by myostatin in adipose-derived stem cells and muscle satellite cells. - PubMed - NCBI

Myostatin (MSTN) is a secreted protein belonging to the transforming growth factor-β (TGF-β) family that is primarily expressed in skeletal muscle and also functions in adipocyte maturation. Studies have shown that MSTN can inhibit adipogenesis in muscle satellite cells (MSCs) but not in adipose-derived stem cells (ADSCs). However, the mechanism by which MSTN differently regulates adipogenesis in these two cell types remains unknown. Peroxisome proliferator-activated receptor-γ (PPARγ) and myogenic differentiation factor (MyoD) are two key transcription factors in fat and muscle cell development that influence adipogenesis. To investigate whether MSTN differentially regulates PPARγ and MyoD, we analyzed PPARγ and MyoD expression by assessing mRNA, protein and methylation levels in ADSCs and MSCs after treatment with 100 ng/mL MSTN for 0, 24, and 48 h. PPARγ mRNA levels were downregulated after 24 h and upregulated after 48 h of treatment in ADSCs, whereas in MSCs, PPARγ levels were downregulated at both time points. MyoD expression was significantly increased in ADSCs and decreased in MSCs. PPARγ and MyoD protein levels were upregulated in ADSCs and downregulated in MSCs. The CpG methylation levels of the PPARγ and MyoD promoters were decreased in ADSCs and increased in MSCs. Therefore, this study demonstrated that the different regulatory adipogenic roles of MSTN in ADSCs and MSCs act by differentially regulating PPARγ and MyoD expression.

I'm very tired though so take my interpretations with a grain of salt at the moment. Actually I'm not the biggest fan of salt; take some KHCO3 instead.

 

[LeeLemonoil]

Thanks Terma for bringing on this connection, worthwhile read

 

[Travis]

The retinoid orphan receptors are primarily melatonin receptors, yet the alpha subtype (RORα) is inhibited by vitamin D and vitamin D-like molecules. Retinoid orphan receptor beta (RORβ) does not respond to steroids, yet is powerfully-inhibited by retinoic acid. Retinoid orphan receptor gamma (RORγ), on the other hand, is inhibted by both vitamin D and retinoic acid.

These receptors had been named based on their similarity to retinoic acid receptors (ROR & ROR), yet they necessarily have different response elements (as you'd expect from retinoic acid being inhibitory on to two of them). All retinoid orphan receptors bind to the response element GGTCA, and besides being differentiated by their antagonist ligands—vitamins A & D—they are sensitive to the nucleotide sequence appearing to the left of the response element (XXXGGTCA). The leftmost sequence must be where other cofactors bind; even though RORs can transcribe solo, they are also known to form heterodimers with other nuclear transcription factors.

Historically there has been doubt surrounding melatonin as its natural ligand, which perhaps had occurred because it had been found incapable of binding the receptor directly (?). However: melatonin always induces transcription in cells expressing a retinoid orphan receptor (ROR) and dNA containing its response element, leading me to propose that melatonin's open-ring breakdown product—(N¹-acetyl-N²-formyl-5-methoxykynuramine)—is in fact the natural ligand. The classic activator besides melatonin has always been doxycycline, and there is some similarity between the molecular structure of said antibiotic and AF-5-methoxykynuramine. There have been detailed studies proving that melatonin is normally oxidized & decyclicized within the cytosol just as you might expect from either enzymatic (pyrrolase) or random superoxide (Ȯ₂⁻) interactions. Melatonin must be metabolized somehow, and there is every indication that its catabolic pathways is similar to serotonin's (its sister indole—representing the daylight phase).

The serotonin-secreting raphe nucleus in the brain begins firing moments before a person opens their eyes and awakens.