Bromocriptine Is Anti-obesity Agent & Reduces Nitric Oxide (NO) Synthesis

[haidut]

Given the role of NO in endotoxin-inflammation-obesity axis, reducing NO synthesis would probably explain a good deal of bromocriptine's anti-obesity, anti-diabetic, and anti-cancer activity. If alpha-adrenergic "receptor" agonism was the main beneficial mechanism in bromocriptine's anti-obesity effects than drugs like clonidine may also have similar effects as they activate the same "receptor".

Bromocriptine inhibits adipogenesis and lipogenesis by agonistic action on α2-adrenergic receptor in 3T3-L1 adipocyte cells - PubMed

"...BC decreased the expression levels of adipogenic activators, including Pparα, Pparγ, and Cebpα, as well as major lipogenic target genes, including Me1, Acc1, 6Pgd, Fasn, and Prkaa1. Moreover, BC markedly reduced intracellular nitric oxide formation in a dose-dependent manner and expression of pro-inflammatory genes, Tnfα and Il6, which reflects attenuated pro-inflammatory responses. Further, upon treatment with BC, D2R-deficient cells displayed a significant decrease in lipogenic activity compared to control cells, whereas yohimbine-treated cells exhibited no reduction in lipogenic activity. BC can effectively attenuate adipogenesis and lipogenesis in 3T3-L1 cells by downregulating the expression of lipogenic genes and proteins. Our current experimental data collectively establish that the anti-obesity effects of BC are not D2R-dependent but result from the action of α2-AR in 3T3-L1 adipocytes."

 

[Agent207]

I wonder why the oversimplification by viewing NO just as good or bad, for what I read about, seems like it depends on more variables.

I.e. the pathway which NO synthesis is stimulated by; is not the same the G-kinase pathway (cGMP and G-kinase mediated, which can have beneficial effects), than peroxynitrite pathway which can be a source of free radicals like hydroxyl and NO2 that may lead to significant oxidative stress.

The same as it would be wise to discern what specific type of NO are we talking about; neuronal (nNOs), endothelial (eNOs) or inducible (iNOs) because their consequences on the body vastly differ.

I think talking about NO without understanding the mechanisms involved in each of them and throwing them all in the same boat is a bit of senseless.

 

[haidut]

post 117120 I wonder why the oversimplification by viewing NO just as good or bad, for what I read about, seems like it depends on more variables.

I.e. the pathway which NO synthesis is stimulated by; is not the same the G-kinase pathway (cGMP and G-kinase mediated, which can have beneficial effects), than peroxynitrite pathway which can be a source of free radicals like hydroxyl and NO2 that may lead to significant oxidative stress.

The same as it would be wise to discern what specific type of NO are we talking about; neuronal (nNOs), endothelial (eNOs) or inducible (iNOs) because their consequences on the body vastly differ.

I think talking about NO without understanding the mechanisms involved in each of them and throwing them all in the same boat is a bit of senseless.

Well, I specifically posted this study since it actually focused on obesity and discusses lowering NO level as beneficial in that context. The physiological purpose of NO is mostly to destroy pathogens, which is usually a short term process (2-3 days). When NO is chronically elevated it is suggestive of CO2 deficiency or another pathological process, and that is certainly not good.

 

[Experienced]

@haidut is Yohimbine good for lowering Serotonin? And lowering fat

 

[Sagitarrius90]

So what's the point of taking bromo if it causes DAWS?

Seems that it's a drug that works wonders but alot of question marks surrounding it and its safety.

 

[Mauritio]

" In HCD-fed diabetic rats, bromocriptine increased D1R and tyrosine hydroxylase (TH) levels in pEWAT and the liver. Besides reducing adiposity, bromocriptine restored GLUT4 and PPARγ levels in pEWAT, as well as postprandial InsR activation and postabsorptive activation of lipid oxidation pathways. A reduction of liver fat, GLUT2 levels and postprandial InsR and AMPK activation in the liver was observed. Increased insulin sensitivity and GLUT4 levels in BAT and an improvement of the overall metabolic status were observed."

Dopamine D2 receptor agonist, bromocriptine, remodels adipose tissue dopaminergic signalling and upregulates catabolic pathways, improving metabolic profile in type 2 diabetes - PubMed

Bromocriptine treatment remodels adipose tissue and the liver dopaminergic system, with increased D1R and TH levels, resulting in higher insulin sensitivity and catabolic function. Such effects may be involved in bromocriptine therapeutic effects, given the impaired expression of dopamine...

pubmed.ncbi.nlm.nih.gov