3 replies to this topic

[Dan1976]

I have just found a study which states that Mirabegron, a selective beta-3 agonist which has already been approved for humans and can be found in drug stores, can activate BAT (Brown Adipose Tissue) and increase RMR by ~200 calories (if taken in a dosage of 200 mg) in normal-weight people.

 

I have already experimented with it (in Europe it is sold under the name Betmiga - there are 25 mg and 50 mg time-released pills which are meant to be taken once per day). When I used it at a dosage of 100-150 mg per day it caused strong thermogenesys, a small drop in blood pressure, vasodilation and it seems to help me while dieting.

 

I am not sure what happens long-term when using beta-3 agonists, however, from one of the studies I read it seems that exposure to an agonist does not downregulate the beta-3 receptor. This means that as you use it, Mirabegron should work the same, and not lose efficiency like other agents like clenbuterol or salbutamol. This could be a good alternative to clenbuterol or salbutamol.

 

When dieting and using Mirabegron to increase your RMR, some synergistic agents could be Yohimbine, T3 and Quercetin (as far as I know).

 

 

Activation of Human Brown Adipose Tissue by a b3-Adrenergic Receptor Agonist

 

Increasing energy expenditure through activation of endogenous brown adipose tissue (BAT) is a potential approach to treat obesity and diabetes. The class of b3-adrenergic receptor (AR) agonists stimulates rodent BAT, but this activity has never been demonstrated in humans. Here we determined the ability of 200 mg oral mirabegron (Myrbetriq, Astellas Pharma, Inc.), a b3-AR agonist currently approved to treat overactive bladder, to stimulate BAT as compared to placebo. Mirabegron led to higher BAT metabolic activity as measured via 18F-fluorodeoxyglucose (18F-FDG) using positron emission tomography (PET) combined with computed tomography (CT) in all twelve healthy male subjects (p = 0.001), and it increased resting metabolic rate (RMR) by 203 ± 40 kcal/day (+13%; p = 0.001). BAT metabolic activity was also a significant predictor of the changes in RMR (p = 0.006). Therefore, a b3-AR agonist can stimulate human BAT thermogenesis and may be a promising treatment for metabolic disease.

 

Full text link: http://libgen.asia/4.../cypess2015.pdf

 

PUBMED: http://www.ncbi.nlm....pubmed/25565203

 

 

Acute and chronic effects of FR-149175, a beta 3-adrenergic receptor agonist, on energy expenditure in Zucker fatty rats

 

(this is the study claiming no downregulation of the receptor)

 

Clinical therapies for both obesity and obese non-insulin-dependent diabetes mellitus require maintenance of reduced body weight after the initial successful reduction resulting from calorie control, exercise, or medication. Although beta(3)-adrenergic receptor (beta(3)-AR) agonists have been shown to stimulate whole body energy expenditure and lipid mobilization, whether stimulatory effects on oxygen consumption and lipolysis are influenced by chronic exposure to agonists has not been fully characterized. We therefore examined the acute and chronic effects of FR-149175, a selective beta(3)-AR agonist, on whole body oxygen consumption in genetically obese Zucker fatty rats. Chronic treatment with FR-149175 caused a decrease in both body weight gain and white fat pad weight at doses that induced lipolysis in acute treatment (1 and 3.2 mg/kg p.o.). Single administration of FR-149175 (0.1, 1, and 3.2 mg/kg p.o.) dose dependently increased whole body oxygen consumption. Repetitive administration did not cause attenuation of the thermogenic response at lower doses (0.1 and 1 mg/kg 2 times daily), whereas the highest dose (3.2 mg/kg 2 times daily) induced a progressive increase in oxygen consumption. PCR analyses of retroperitoneal white adipose tissue indicated little or no change in beta(3)-AR mRNA levels. Uncoupling protein 1 gene expression increased at 1 mg/kg, and drastic upregulation was detected at 3.2 mg/kg. FR-149175 also increased HSL mRNA levels in a dose-related manner, whereas there was no effect on genes involved in beta-oxidation. These results support that the thermogenic effect of beta(3)-AR agonists is not attenuated by chronic exposure to agonists.

 

Full text link: http://ajpregu.physi...tent/287/2/R336

 

PUBMED: http://www.ncbi.nlm....pubmed/15271680

 

 

Edited by Dan1976, 11 March 2015 - 12:18 PM.

[Darryl]

I would expect synergy from pro-retinol carotenes, fucoxanthin (found in wakame seaweed), menthol (or peppermint), methionine restriction, cold exposure, and capscinoids, which all appear to work downstream of the β3-adrenergic receptor in non-shivering thermogenesis via mitochondrial uncoupling in brown adipose tissue.

 

Serra, F., Bonet, M. L., Puigserver, P., Oliver, J., & Palou, A. (1999). Stimulation of uncoupling protein 1 expression in brown adipocytes by naturally occurring carotenoids. International journal of obesity, 23, 650-655.

Treatment with b-carotene, a-carotene and lutein promoted UCP1 expression in a dose-dependent manner, with an effectiveness that was related to their potency as vitamin A precursors.

 

 

Maeda, H., Hosokawa, M., Sashima, T., Funayama, K., & Miyashita, K. (2005). Fucoxanthin from edible seaweed, Undaria pinnatifida, shows antiobesity effect through UCP1 expression in white adipose tissues.Biochemical and biophysical research communications, 332(2), 392-397.

We show reduction of abdominal white adipose tissue (WAT) weights in rats and mice by feeding lipids from edible seaweed, Undaria pinnatifida. Clear signals of UCP1 protein and mRNA were detected in WAT of mice fed the Undaria lipids, although there is little expression of UCP1 in WAT of micefed control diet. The Undaria lipids mainly consisted of glycolipids and seaweed carotenoid, fucoxanthin. In the fucoxanthin-fed mice, WAT weight significantly decreased and UCP1 was clearly expressed in the WAT, while there was no difference in WAT weight and little expression of UCP1 in the glycolipids-fed mice.

 

 

Ma, S., Yu, H., Zhao, Z., Luo, Z., Chen, J., Ni, Y., ... & Zhu, Z. (2012). Activation of the cold-sensing TRPM8 channel triggers UCP1-dependent thermogenesis and prevents obesity. Journal of molecular cell biology, 4(2), 88-96.

Challenging brown adipocytes with menthol, a TRPM8 agonist, up-regulates UCP1 expression and requires protein kinase A activation. Upon mimicking long-term cold exposure with chronic dietary menthol application, menthol significantly increased the core temperatures and locomotor activity in wild-type mice; these effects were absent in both TRPM8−/− and UCP1−/− mice. Dietary obesity and glucose abnormalities were also prevented by menthol treatment.

 

 

Wanders, D., Burk, D. H., Cortez, C. C., Van, N. T., Stone, K. P., Baker, M., ... & Gettys, T. W. (2015). UCP1 is an essential mediator of the effects of methionine restriction on energy balance but not insulin sensitivity. The FASEB Journal, fj-14.

Energy expenditure (EE) did not differ between wild-type (WT) and Ucp1^−/− mice on the control diet, but methionine restriction (MR) increased EE by 31% and reduced adiposity by 25% in WT mice. In contrast, MR failed to increase EE or reduce adiposity in Ucp1^−/−mice.

 

 

Yoneshiro, T., Aita, S., Matsushita, M., Kayahara, T., Kameya, T., Kawai, Y., ... & Saito, M. (2013). Recruited brown adipose tissue as an antiobesity agent in humans. The Journal of clinical investigation, 123(123 (8)), 3404-3408.

Acute cold exposure at 19°C for 2 hours increased energy expenditure (EE). Cold-induced increments of EE (CIT) strongly correlated with BAT activity independently of age and fat-free mass. Daily 2-hour cold exposure at 17°C for 6 weeks resulted in a parallel increase in BAT activity and CIT and a concomitant decrease in body fat mass. Changes in BAT activity and body fat mass were negatively correlated. Similarly, daily ingestion of capsinoids for 6 weeks increased CIT. These results demonstrate that human BAT can be recruited even in individuals with decreased BAT activity, thereby contributing to body fat reduction.

 

 

 

 

 

Edited by Darryl, 11 March 2015 - 02:54 PM.

[Darryl]

Here's a good review of the whole field:

 

Bonet, M. L., Oliver, P., & Palou, A. (2013). Pharmacological and nutritional agents promoting browning of white adipose tissue. Biochimica et Biophysica Acta (BBA)-Molecular and Cell Biology of Lipids, 1831(5), 969-985.

 

Potentiallly therapeutic options are mentioned:

 

β3 adrenergic agonists (mirabegron, solabegron)

PPARγ agonists (benzafibrate, pioglitazone)

AMPK activation (exercise, fasting, metformin, berberine, salicylates, telmisartan, dietary polyphenols)

capsaicin and capsaicin-analogs

fucoxanthin

retinoids

dietary methionine restriction

cold exposure

Edited by Darryl, 11 March 2015 - 03:31 PM.

[Multivitz]

Parasites! No, not you.