Adipose tissue agonist

D5 has slightly different properties than D4, and it does not have any estrogenic activity [289]. It does, however, also have adverse effects on the reproductive system, much like D4, but also on the adipose tissue, bile production, and even immune system due to D5 s effect of reducing the prolactin levels [291]. In addition, it was determined that D5 causes a significant increase in uterine tumors in rats after a 160 ppm exposure. However, it is proposed that the tumors occur in rats through a mechanism that would not affect humans [291]. D5 also acts as a dopamine agonist and it can cause adverse effects on the nervous system in humans [291]. For exposures to D6 in rats, an increase in liver and thyroid mass and reproductive effects were observed [292]. 

The release of free fatty acids from adipose tissue (lipolysis) is mediated through (33-adrenoceptors. Isoproterenol is the most potent agonist, followed by epinephrine and norepinephrine. 

Beta3 adrenoceptor agonists Increased lipolysis and thermogenesis in adipose tissue, but disappointing results in clinical trials... 

Clomiphene citrate, a partial estrogen agonist, is closely related to the estrogen chlorotrianisene (Figure 40-3). This compound is well absorbed when taken orally. It has a half-life of 5-7 days and is excreted primarily in the urine. It exhibits significant protein binding and enterohepatic circulation and is distributed to adipose tissues. 

We have observed that suppression of elevated FFA levels is a very rapid (less than 12 hour) response to treatment of insulin-resistant rats with PPARy agonists (T. Doebber, unpublished data). Since PPARy agonists are known to promote adipose tissue uptake and storage of fatty acids, it is plausible that this effect constitutes a major mechanism of insulin sensitization, whereby elevated FFAs—a known cause of hepatic and muscle insulin resistance—can be alleviated. An additional effect of in vivo PPARy activation, shown to occur in rats, was an increase in the number of small white adipocytes, along with a relative shift in the size of visceral (decreased) versus subcutaneous (increased) adipose depots (73). This has important implications because visceral adiposity and larger fat cells are both associated with insulin resistance. 

The paradigm used by Ahlquist for classifying receptors based on their pharmacological characteristics (i.e., rank order of potency of agonists) was further developed by Lands and colleagues with the subdivision of the P-adrenergic receptors into pr and P2-subtypes (12). The pradrenergic receptor, the dominant receptor in heart and adipose tissue, was equally sensitive to epinephrine and... 

Himms-Hagen J, Cui J, Danforth E Jr, et al. Effect of CL-316,243, a thermogenic P3-agonist, on energy balance and brown and white adipose tissues in rats. Am J Physiol 1994 266 R1371-R1382. 

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