SR9009 - What does it do and how?


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SR9009 - a special SARM that does amazing things. I love reading PubMed, so that will be my major source of information about SR9009. Let's dive into it, shall we? When I have multiple quotes from one source, I will reference the source after the last quote.

Based on the alterations in energy metabolism and gene expression we observed in normal C57BL6 and Balb/c mice, we sought to examine whether a REV-ERB***945;/***946; agonist would be efficacious in a rodent model of obesity. We initiated the study with 20-week old C57BL6 mice (average weight = 41g) that had been maintained on a high fat diet for 14 weeks (20% carbohydrate 60% fat). The mice continued on the HF diet and we initiated twice per day dosing (i.p.) of SR9009. While the stress of handling and twice-daily injections caused weight loss in vehicle-treated controls, weight loss of SR9009-treated animals was 60% greater.

Obese mice using SR9009, kept on their high fat diet the entire time, saw a 60% GREATER weight loss than those who were not on it. The stress of being handled and such causes mice to greatly increase their metabolism and lose weight. Those with SR9009 lost a LOT more. This means SR9009 is great for fat loss.

In addition to the decrease in fat mass we also observed a 12% decrease in plasma triglycerides (TGs) and a 47% decrease in plasma total cholesterol (Chol) (Fig. 5c). Plasma non-esterified fatty acids (NEFA) were also reduced (23%) along with plasma glucose (19%) in the SR9009 treated animals (Fig. 5c). There was also a trend toward a decrease in plasma insulin levels (35%). Consistent with the decrease in adipocity we also noted an 80% decrease in plasma leptin and a decrease (72%) in the proinflammatory cytokine IL-6 (Fig. 5d). Examination of plasma triglycerides and total cholesterol in lean mice also demonstrated the ability of SR9009 and SR9011 to reduce the levels of these lipids (Figs. 5e, 5f). Consistent with the decreased plasma TGs and total Chol we observed a significant decrease in the expression of genes encoding lipogenic enzymes (Fasn and Scd1) as well as cholesterologenic regulatory proteins (Hmgcr and Srebf2) with SR9009 treatment (Fig. 5g). In the WAT, SR9009 treatment resulted in a decrease in expression of genes encoding enzymes involved in TG synthesis (Fig. 5g) as was also observed in lean mice (Fig. 4d). Similar to our observations in lean mice (Fig. 4c), we observed that the REV-ERB agonist induced the expression of genes involved in fatty acid and glucose oxidation (Cpt1b, Ucp3, Ppargc1b, Pkm2 and Hk1) (Fig. 5g). Taken together with the results from the CLAMS experiments (Fig. 3), these data suggest that REV-ERB agonists increase energy expenditure by increasing fatty acid and glucose oxidation in the skeletal muscle. The gene expression data is also consistent with decreased TG synthesis in the liver and WAT as well as a reduction in hepatic cholesterol synthesis. We also examined the effects of SR9009 in a genetic model of obesity (ob/ob mice) and after 12-days of dosing we observed that SR9009 suppressed the degree of weight gain normally observed in this leptin deficient mouse with no significant alterations in glucose or insulin tolerance (Fig. 5h and data not shown).

Other than fat percentage, what else went down? Well, just about everything bad did. Triglicerides dropped by 12%, Cholesterol dropped by 47%, blood sugar (glucose) dropped by 19%. Leptin dropped by 80% and cytokine (which helps cause inflammation) dropped by 72%. No change in glucose or insulin tolerance was seen, which is very important.

But what is this REV-ERB stuff you keep reading about? Well, basically, it controls metabolism and the circadian rhythm of your body. SR9009, through REV-ERB represses orexinergic gene expression. Why is this good?

. Given the intrinsic negative side effects associated with excessive motivation for food and lack of sleep, including anxiety, obesity, diabetes, and low self-esteem, our experiments suggest that the REV-ERB regulation of the orexin pathway may hold utility in ameliorating the detrimental effects of imbalanced circadian behavior via orexinergic pathways.

Wow, ok, orexinergic genes, when out of wack, cause overeating, insomnia, anxiety, obesity, diabetes, and low self esteem! What else does it do?

Administration of the REV-ERB agonist, SR9009, at ZT0 (testing start time of zero) affects expression of orexinergic genes in the brain over a 24-hour period. We recently demonstrated that acute injections at ZT6, which corresponds to peak REV-ERB mRNA expression, results in increased wakefulness and locomotion. Orexin signaling via OX1R in the striatum and nucleus accumbens is associated with reward feeding and addictive behavior toward nicotine and other drugs [72–74]. In line with this, our lab recently demonstrated that administration of SR9009 injection decreased the addictive phenotypic properties of cocaine

SR9009 helps you feel more awake and you feel like moving around more. It also reduces the addictiveness of nicotine and cocaine (and other addictive drugs).

SR9009 greatly helps in reducing body fat, cholesterol level, triglicerides, and blood sugar. It helps you feel more awake and feel more like moving around and doing stuff. It reduces insomnia and binge eating, as well as the anxiety and low self esteem that come from those things. It really is a great SARM!